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Background: Concomitance of celiac disease (CD) and IgE-mediated wheat allergy is described in some case reports. The objective was to evaluate the frequency of sensitization to wheat, rye, barley, and malt in children and adolescents with CD., Methods: Measurement of serum levels of specific IgE to wheat, rye, barley, and malt (ImmunoCAP; sensitization IgE ≥0.35 kUA/L) in CD patients followed in specialized clinics to verify allergy history, general characteristics, small bowel biopsy characteristics, compliance with gluten-free diet (GFD), and occurrence of symptoms in case of noncompliance., Results: We evaluated 74 patients; the median of age and age at diagnosis of CD were 8.6 years (5.0-12.8) and 3.6 years (1.6-7.0), respectively. Median time of GFD was 3.5 years (1.4-5.8). History of asthma occurred in 17.3% of subjects, allergic rhinitis in 13.5%, and AD in 5.4%. Frequency of sensitization was 4% for wheat, 10.8% for rye, 5.4% for barley, and 2.7% for malt. There was no association between wheat sensitization and age at diagnosis, time of GFD, small bowel biopsy characteristics, allergy history, and gluten consumption. There was no relationship between sensitization to wheat and occurrence of immediate symptoms when not complying with GFD., Conclusion: In conclusion, the frequency of sensitization to wheat, rye, barley, and malt in CD patients was 4, 10.8, 5.4, and 2.7%, respectively. Therefore, to ensure that cutaneous and respiratory contact with wheat is safe, we advise patients with CD to investigate their sensitivity to wheat, rye, and barley because not all patients with CD are allergic to these cereals., (© 2020 S. Karger AG, Basel.)

The intestinal microbiota plays a critical role in food allergy development. However, little is known regarding the structure and composition of the intestinal microbiota in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA). We examined the gut microbiota alterations in patients with WDEIA and the microbiota's association with WDEIA. Fecal samples were collected from 25 patients with WDEIA and 25 healthy controls. Environmental exposure factors were obtained, serum total IgE, IgE specific to wheat, gluten, and ω-5 gliadin were measured. Fecal samples were profiled using 16S rRNA gene sequencing. The relative abundances of the bacterial genera Blautia (P < 0.05), Erysipelatoclostridium (P < 0.01), Akkermansia (P < 0.05) and Lachnospiraceae&#95;NK4A136&#95;group (P < 0.05) were significantly increased, while those of Lactobacillus (P = 0.001) and Dialister (P < 0.05) were significantly decreased in subjects with WDEIA. The microbial diversity did not differ between WDEIA patients and healthy controls. IgE specific to ω-5 gliadin was positively associated with the Oscillospira (r = 0.48, P < 0.05) and negatively associated with Leuconostoc (r = -0.49, P < 0.05). Total IgE levels were significantly negatively correlated with Bifidobacterium (P < 0.05). The gut microbiome compositions in WDEIA patients differed from those of healthy controls. We identified a potential association between the gut microbiome and WDEIA development. Our findings may suggest new methods for preventing and treating WDEIA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Gastrointestinal (GI) and extra-GI symptoms/manifestations represent key clinical features of patients with non-celiac gluten/wheat sensitivity (NCG/WS). This study aimed to investigate neuro-immune (focusing on mast cells, MCs) interactions in the duodenal submucosa of patients with NCG/WS., Methods: Submucosal whole mounts from duodenal biopsies of 34 patients with self-reported NCG/WS, 28 with celiac disease (CD), 13 with functional dyspepsia (FD), and 24 healthy controls (HC) were analyzed by immunohistochemistry. Quantitative data on neuronal and MCs density and the percentage of MCs in close vicinity to nerves were obtained, and correlations among neurons, MC density and MC-nerve distance (D), and symptoms were assessed in the three groups., Key Results: The number of submucosal neurons was not different among groups. In NCG/WS, MC density was not different from HC, while it was slightly increased vs. CD (P = .07) and significantly decreased vs. FD (P < .05). The percentage of MCs close to nerves (D < 15 µm) was similarly increased in all three pathological groups vs. HC (P < .001). In NCG/WS, MC infiltration correlated with bloating (P = .001) and abdominal pain severity (P = .03) and the percentage of MCs in proximity to neurons correlated with the number of GI symptoms (D < 5 µm; P = .05), bloating and abdominal pain severity (D < 15um; P = .01)., Conclusions and Inferences: Submucosal MC infiltration and the close (within 15 µm) MC-to-nerve proximity in the duodenum of NCG/WS patients are features providing a histopathological basis to better understand GI symptoms in this condition., (© 2020 John Wiley & Sons Ltd.)

Objective: To investigate the association of single nucleotide polymorphisms (SNPs) at the interleukin (IL)-18 locus with wheat-dependent exercise-induced anaphylaxis (WDEIA) in the Han Chinese population., Method: 130 patients with WDEIA and 600 healthy subjects were recruited for this study. Three tag SNPs (rs360729, rs360717 and rs1946518) were selected and genotyped, and total IgE and specific IgE levels were measured using the ImmunoCAP system., Results: After Bonferroni correction, the frequency of the G-allele in rs1946518 in the WDEIA group was significantly higher than that in control group (P = 0.0015). Genotypic distributions of rs1946518 significantly differed between WDEIA and control groups, and compared with the TT genotype, the homozygote GG genotype was associated with a higher risk of WDEIA (P = 0.0031). At position rs1946518, the log-transformed total IgE values were significantly higher in the group with the heterozygous GT genotype than in TT genotype group (P = 0.0024). Haplotype AGG formed by three SNPs alleles occurred significantly more frequently in WDEIA group than in control group (P = 0.003)., Conclusion: The minor allele G at position rs1946518 might serve as a marker for the risk of WDEIA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Little is known regarding food anaphylaxis in infancy. We aimed to describe specificities of food anaphylaxis in infants (≤12 months) as compared to preschool children (1-6 years)., Methods: We conducted a retrospective study of all food anaphylaxis cases recorded by the Allergy Vigilance Network from 2002 to 2018, in preschool children focusing on infants., Results: Of 1951 food anaphylaxis reactions, 61 (3%) occurred in infants and 386 (20%) in preschool children. Two infants had two anaphylaxis reactions; thus, we analyzed data among 59 infants (male: 51%; mean age: 6 months [SD: 2.9]); 31% had a history of atopic dermatitis, 11% of previous food allergy. The main food allergens were cow's milk (59%), hen's egg (20%), wheat (7%) and peanut (3%) in infants as compared with peanut (27%) and cashew (23%) in preschool children. Anaphylaxis occurred in 28/61 (46%) cases at the first cow's milk intake after breastfeeding discontinuation. Clinical manifestations were mainly mucocutaneous (79%), gastrointestinal (49%), respiratory (48%) and cardiovascular (21%); 25% of infants received adrenaline. Hives, hypotension and neurologic symptoms were more likely to be reported in infants than in preschool children (P = .02; P = .004; P = .002, respectively). Antihistamines and corticosteroids were more often prescribed in preschool children than in infants (P = .005; P = .025, respectively)., Conclusion: Our study found that in infants presenting with their first food allergy, in a setting with a high rate of infant formula use, the most predominant trigger was cow's milk. As compared to older preschool children, hives, hypotonia and hypotension were more likely to be reported in infants. We believe that this represents a distinct food anaphylaxis phenotype that can further support developing the clinical anaphylaxis criteria in infants., (© 2019 John Wiley & Sons Ltd.)

In recent years, the role of atopic dermatitis epidermal skin barrier defects in inducing a transcutaneous allergic sensitization is highly debated, possibly explaining why some children with eczema are sensitized to foods they have never eaten. In our specific situation, the association between coeliac disease and wheat allergy might be particularly harmful owing to unavoidable strict food avoidance. We describe the case of a young boy affected by coeliac disease who, after an occasional unexpected ingestion of gluten, experienced a complete anaphylactic reaction characterized by urticarial, labial angioedema, wheezing, and hypotension. To better investigate the state of allergic sensitization to wheat in our patient, we then performed the component resolved diagnosis, which showed Tri a19 2 kU/l and Tri a14 0.3 kU/l. These results demonstrated the association of IgE-mediated allergy to wheat and coeliac disease. The natural course of specific IgE in allergic patients who are on a food-free diet needs further investigation, such as the possible influence that the increasing popularity of gluten-free diets may have on the epidemiology of wheat allergy in westernized societies. National and International registers of cases of anaphylaxis may improve the still limited knowledge in this field. The final message of our contribution is that the decision to eliminate a food should to take into account a patient's awareness of possible consequences.

Food allergy (FA) is a serious health problem, and its incidence has been increasing especially in children. Wheat is one of the five most common foods that trigger allergic reactions in children. It is an increasingly recognised trigger for immune-mediated FAs, both Immunoglobulin E (IgE) and non-IgE mediated. We describe the case of a 4-year-old boy with a combination of symptoms due to IgE-mediated asthma worsened by IgE-non-dependent hypersensitivity to wheat demonstrated by a positive patch test. With the avoidance of wheat oral intake, we observed a progressive clinical improvement. To the best of our knowledge, this is the first report of a patient with IgE-non-dependent allergy to wheat presenting with chronic symptoms in one body system outside of the gastrointestinal tract and with negative skin prick test., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe and potentially life-threatening allergy caused by wheat ingestion and most commonly in combination with exercise., Objective: To investigate the role and impact of different cofactors (exercise, aspirin, and alcohol) in patients with WDEIA., Methods: We studied 25 adult patients with WDEIA. Diagnostic workup included specific IgE to omega-5 gliadin and skin prick test with wheat flour and gluten. Titrated oral challenge was performed with gluten at rest, combined with treadmill exercise, aspirin, alcohol, or a combination of exercise and aspirin., Results: A positive challenge to gluten was found at rest (without cofactors) in 48% (12 of 25), with exercise in 92% (23 of 25), with aspirin in 84% (21 of 25), with alcohol in 56% (9 of 19), and with a combination of exercise and aspirin in 82% (18 of 22) of the patients. With exercise as a cofactor, the median threshold was 24 g (range, 4.8-80 g), with aspirin 8 g (range, 2.4-80 g), and with alcohol 28 g (range, 0-45 g). The combination of 2 cofactors (exercise and aspirin) resulted in a median threshold of 4.3 g (range, 1.1-48 g). The threshold for the clinical reaction was lowered by 63%, 83%, 36%, and 87%, respectively, compared with at rest. The mean severity grade (scale 0-5) according to the Sampson severity score at rest was 0.8 (range, 0-2), and when combined with exercise 2.1 (range, 0-5), with aspirin 1.9 (range, 0-5), with alcohol 0.8 (range, 0-2), and with the combination of exercise and aspirin 1.5 (range, 0-2)., Conclusion: Our results demonstrate that exercise and aspirin augment clinical reactions in WDEIA by lowering the threshold and increase the severity of the allergic reaction, whereas alcohol gives ambiguous results. Furthermore, a combination of 2 cofactors (exercise and aspirin) increases the risk of reactions., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: MMW: grant/research support: Prometheus Laboratories Inc (Irritable bowel syndrome (IBS Diagnostic), Commonwealth Diagnostics International (Biomarkers for FGIDs). SK: grant/research support: Cancer Institute NSW (Career Development Fellowship), National Health and Medical Research Council (Project Grant APP1128487) Commonwealth Diagnostics International (Biomarkers for FGIDs), Syntrix Biosystems (contract research, drug delivery). NJT: grant/research support: Rome Foundation; Abbott Pharmaceuticals; Datapharm; Pfizer; Salix (Irritable bowel syndrome); Prometheus Laboratories Inc (Irritable bowel syndrome (IBS Diagnostic)); Commonwealth Diagnostics International (Biomarkers for FGIDs); Janssen (Constipation). Consultant/Advisory Boards: Adelphi Values (Functional dyspepsia (patient-reported outcome measures)); GI therapies (Chronic constipation (Rhythm IC)); Allergens PLC; Napo Pharmaceutical; Outpost Medicine; Samsung Bioepis; Yuhan (IBS); Synergy (IBS); Theravance (Gastroparesis); IM Health Sciences (dyspepsia). Patent Holder: Biomarkers of irritable bowel syndrome, Licensing Questionnaires (Mayo Clinic Talley Bowel Disease Questionnaire, Mayo Dysphagia Questionnaire); Nestec European Patent (Application No. 12735358.9); Singapore ‘Provisional’ Patent (NTU Ref: TD/129/17 ‘Microbiota Modulation of BDNF Tissue Repair Pathway’).

Gluten related disorders (GRD) represent a wide spectrum of clinical manifestations that are triggered by the ingestion of gluten. Coeliac disease (CD) or gluten sensitive enteropathy is the most widely recognised, but extra-intestinal manifestations have also been increasingly identified and reported. Such manifestations may exist in the absence of enteropathy. Gluten sensitivity (GS) is another term that has been used to include all GRD, including those where there is serological positivity for GS related antibodies in the absence of an enteropathy. Gluten ataxia (GA) is the commonest extraintestinal neurological manifestation and it has been the subject of many publications. Other movement disorders (MDs) have also been reported in the context of GS. The aim of this review was to assess the current available medical literature concerning MDs and GS with and without enteropathy. A systematic search was performed while using PubMed database. A total of 48 articles met the inclusion criteria and were included in the present review. This review highlights that the phenomenology of gluten related MDs is broader than GA and demonstrates that gluten-free diet (GFD) is beneficial in a great percentage of such cases.

Celiac disease (CD) and concomitant wheat allergy are not commonly described in the literature. Both can have almost the same treatment consisting of a gluten-free or wheat-free diet. On the other hand, they are based on totally different pathogenetic mechanisms and can be easily underdiagnosed, particularly CD. We describe a peculiar case of a young female patient affected by wheat allergy whose serological and histological data were not diagnostic for CD. Organ culture system successfully detected specific antibodies for CD in duodenal biopsy supernatant, supporting the diagnosis of CD.

Objectives: Wheat avoidance in the absence of celiac disease (CD) is common but occurrence of concurrent functional gastrointestinal disorders (FGIDs) in this group is uncertain. The aims of this study were to determine the prevalence of self-reported wheat or gluten sensitivity and doctor diagnosed CD in an Australian population, define the associated gastrointestinal (GI) symptoms and FGIDs, and determine the relationship between self-reported wheat sensitivity, demographic and medical factors., Methods: A total of 3542 people randomly selected from the Australian population returned a mail survey which contained questions on wheat avoidance, GI symptoms, demographic, medical, and lifestyle factors. We defined self-reported wheat sensitivity as people who reported gastrointestinal symptoms on ingestion of wheat based foods, but did not suffer from celiac disease, inflammatory bowel disease or colorectal cancer. Functional dyspepsia (FD) and irritable bowel syndrome (IBS) were diagnosed by Rome III criteria. CD status was self-reported., Results: The prevalence of self-reported wheat sensitivity in this cohort was 14.9% (95% CI 13.7-16.2). The prevalence of CD was 1.2% (95%CI 0.8-1.6). Doctor diagnosed CD was significantly associated with a diagnosis of FD (OR 3.35, 95%CI 1.72-6.52) and IBS (OR 2.28, 95%CI 1.08-4.81). Those with self-reported wheat sensitivity were more likely to report multiple abdominal symptoms (of the 18 assessed) than those without (3.9 symptoms with self-reported wheat sensitivity vs. 1.6 without, p = 0.0001). In a multivariate analysis, self-reported wheat sensitivity was independently associated with IBS (OR 3.55, 95%CI 2.71-4.65) and FD (1.48, 95%CI 1.13-1.94)., Conclusions: Self-reported wheat sensitivity is common, with a prevalence of 14.9% in this cohort. There is a strong association between both celiac disease and self-reported wheat sensitivity, and chronic gastrointestinal symptoms, as well as a diagnosis of FD and IBS.

Background: Wheat-dependent, exercise-induced anaphylaxis (WDEIA) is a severe form of allergy in which exercise is being considered as mandatory. The diagnosis is often complex and the clinical reproducibility low., Objective: The aims of this study were to establish a standardized challenge method for the diagnosis of WDEIA and to investigate whether exercise is an essential trigger factor or alternatively an augmentation factor able to lower threshold and increase severity., Methods: We investigated 71 patients (age, 18.6-73.7 years) with a case history of WDEIA. Skin prick test (SPT) and measurement of specific IgE (sIgE) were followed by an oral food challenge with gluten at rest and in combination with treadmill exercise., Results: A clinical reaction was elicited in 47 of 71 (66%), and in 26 of these (37%) the reaction could be elicited at rest. The median dose required at rest was 48 g (8-80 g) and in combination with exercise 24 g (4-80 g). Severity was significantly higher with exercise (2.3) than at rest (1.1) using Sampson severity score. In the challenge, SPT was positive to wheat in 93.6% (44 of 47) and to gluten in 95.7% (45 of 47). sIgE to wheat, gliadin, and omega-5 gliadin was present in 78.7% (37 of 47), 76.5% (36 of 47), and 91.4% (43 of 47) of the patients. Receiver operating characteristic-curve analysis for sIgE to omega-5 gliadin, a component of the gluten fraction and the major allergen in WDEIA, showed best sensitivity (91%) and specificity (92%) when gluten was combined with exercise., Conclusions: A challenge test with gluten at rest and combined exercise is a safe confirmatory test for WDEIA. A reaction can be elicited at rest (without exercise), but exercise is able to lower the threshold and increase the severity., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Serum IgG and IgA food antibodies have been used for dietary advice to subjects with gastrointestinal symptoms and perceived food intolerance, but the role of these antibodies in mediating intolerance is controversial. The present study investigated associations between perceived gastrointestinal intolerance to milk-or wheat and the corresponding s-IgG and s-IgA food antibodies in subjects with morbid obesity., Methods: Subjects with morbid obesity (BMI ≥ 40 kg/m 2 or ≥35 kg/m 2 with obesity-related complications) were included. Irritable Bowel Syndrome (IBS) was diagnosed based on the Rome III criteria. Severity of specific gastrointestinal symptoms were measured with the Gastrointestinal Symptom Rating Scale (GSRS)-IBS. S-IgG against cow's milk, cheese, wheat and gluten, and s-IgA against casein and gliadin were measured., Results: Ninety-seven subjects (80 females) with mean age 45 (SD 8.4) years were included, 70 had gastrointestinal complaints, 25 had IBS, and 22 and 20 reported milk- and wheat- intolerance respectively. There were no significant differences in serum concentrations or proportions of subjects above defined cut-off values for the antibodies between subjects with and without gastrointestinal complaints. In the group with gastrointestinal complaints, no significant differences were found between subjects with and without perceived food intolerance. Except for a significant correlation between IgG against cheese and GSRS-diarrhea (Rho: -0.25, P = 0.04), no significant correlations were found between the antibodies and type or degree of gastrointestinal symptoms, including IBS., Conclusions: The study showed no associations between perceived milk or wheat intolerance and the corresponding s-IgG and s-IgA food antibodies in subjects with morbid obesity.

Background: Specific immunoglobulin E (IgE) sensitization to wheat is more common than a doctor's confirmed wheat allergy and is also frequently observed in grass pollen-allergic patients (pollinosis patients). Thus, the objective of this study was to investigate the level and feature of serological IgE cross-reactivity between grass pollen and wheat in a cohort of pollinosis subjects with no diagnosis of wheat allergy., Methods: Seventy-two children, aged 5-17 years, with a doctor's diagnosis of pollinosis, IgE towards grass pollen, and currently eating wheat were recruited. Serum samples were analyzed for IgE against wheat, timothy grass/wheat-specific allergen components, Pru p 3, and cross-reactive carbohydrate determinants (CCD) and specific IgE-binding inhibition experiments were performed., Results: Sixty percent of the grass pollen subjects were sensitized to wheat with a median of 0.5 kUA/L. Wheat-sensitized subjects were more often sensitized to the two allergens, Phl p 12 and CCD, known to be cross-reactive between grass and wheat. Sensitizations to seven wheat-specific allergens derived from the gluten fraction were, with the exception of one individual, only found in wheat-sensitized subjects. These subjects also more often reported current and past history of allergy to staple foods (milk, egg, wheat, soy, and fish)., Conclusion: Wheat sensitization caused by cross-reactivity but also by sensitization to wheat-specific allergens was common in the grass-allergic children and also associated with allergy to staple foods other than wheat. The results indicate the presence of a subgroup of pollinosis patients with simultaneous sensitization to wheat and food allergy not only caused by cross-reactions., (© 2018 S. Karger AG, Basel.)

Background:  Non-celiac wheat sensitivity (NCWS) is a new clinical entity in the world of  gluten-related diseases. Nickel, the most frequent cause of contact allergy, can be found in wheat  and results in systemic nickel allergy syndrome and mimics irritable bowel syndrome (IBS).  Objective: To evaluate the frequency of contact dermatitis due to nickel allergy in NCWS patients  diagnosed by a double-blind placebo-controlled(DBPC)challenge,and to identify  the  characteristics  of  NCWS  patients  with  nickel  allergy.  Methods: We performed  a prospective study  of 60 patients (54 females, 6 males; mean age 34.1 ± 8.1 years) diagnosed with NCWS from  December  2014 to November 2016; 80 age- and sex-matched subjects with functional gastrointestina l symptoms served as controls. Patients reporting contact dermatitis related to nickel-containing objects  underwent  nickel  patch  test  (Clinicaltrials.gov  registration number: NCT02750735)., Results:   Six  out  of  sixty  patients  (10%)  with  NCWS  suffered  from contact dermatitis and  nickel allergy  and  this  frequency  was  statistically  higher (p = 0.04)than observed in the control group(5%. The main clinical characteristic of  NCWS  patients with nickel allergy was a  higher frequency  of  cutaneous  symptoms  after  wheat ingestion compared to NCWS patients who did not suffer  from  nickel  allergy  (p < 0.0001., Conclusions:  Contact dermatitis and nickel allergy  are more  frequent  in  NCWS  patients than  in  subjects  with  functional gastrointestinal disorders;furthermore, these patients had a very high frequency of cutaneous manifestations after wheat  ingestion.  Nickel  allergy  should  be  evaluated  in  NCWS  patients  who  have  cutaneous  manifestations after wheat ingestion.

Anaphylaxis is a severe allergic reaction that is rapid in onset and might cause death. Although wheezes, dyspnea or loss of consciousness are known to occur with severe allergic reactions with IgE-mediated food allergy, reports of apnea attack associated with IgE-mediated food allergy are rare. In this case, 9-year-old boy with IgE-mediated wheat allergy experienced apnea attack with strong desaturation after an immediate allergic reaction including erythema, abdominal pain, vomiting, and anaphylactic shock. The patient had asphyxia and cyanosis confirmed by medical staff when his oxygen saturation decreased to the 60% level, and he had occasional asphyxia over 10 seconds with no thoracic motion after a desaturation episode. Central apnea attack might be occurred in patient with IgE-mediated food allergy. However, the exact mechanism responsible remains unknown and further research is needed.

Celiac disease (CD) determines neurologic manifestations in 10% of all CD patients. We describe the most common clinical manifestations as cerebellar ataxia, gluten encephalopathy, multiple sclerosis, peripheral neuropathies, sensorineural hearing loss, epilepsy, headache, depression, cognitive deficiencies and other less described clinical conditions. Our aim is to perform, as more as possible, a review about the most recent update on the topics in international literature. It is important to consider clinical neurological manifestations in celiac patients and to research these conditions also in the follow-up because they may start also one year after the start of gluten free diet (GFD) as peripheral neuropathy. The association with autism is analysed and possible new association with non-celiac gluten sensitivity (NCGS) are considered.

Background: Wheat is one of the most common food allergens in early childhood. In contrast to other food allergies, wheat-specific IgE correlates badly with clinical symptoms and relevant components have been identified mostly for wheat-depended exercise-induced anaphylaxis. Moreover, a high percentage of patients present with immediate type symptoms but wheat-specific IgE cannot be detected with commercial available systems., Objective: We addressed the question whether the IgE recognition pattern between wheat allergic (WA) and clinically tolerant (WT) children differs in order to identify individual proteins useful for component-resolved diagnostics., Methods: Sera of 106 children with suspected wheat allergy, of whom 44 children had clinical relevant wheat allergy and 62 were tolerant upon oral food challenge, were analyzed for wheat-specific IgE using the ImmunoCap system as well as immunoblots against water and salt soluble, and water-insoluble protein fractions. 40 randomly selected sera were analyzed for specific IgE to ω5-gliadin., Results: Sixty-three percent of the WT and 86% of the WA children were sensitized to wheat with >0.35 kUA /l in ImmunoCAP analysis. We could confirm the role of α-, ß-, γ-, and ω-gliadins, and LMW glutenin subunits as major allergens and found also IgE binding to a broad spectrum of water- and salt-soluble protein bands. It is of great importance that wheat allergic and tolerant patients showed IgE binding to the same protein bands. WT and WA did not significantly differ in levels of ω5-gliadin-specific IgE., Conclusions & Clinical Relevance: Children with challenge proven clinical relevant food allergy and tolerant ones had a similar spectrum of IgE binding to the same protein bands. These findings imply that component-resolved diagnostics might not be helpful in the diagnostic work-up of wheat allergy., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a rare, but potentially severe food allergy exclusively occurring when wheat ingestion is accompanied by augmenting cofactors. It is clinically characterized by anaphylactic reactions ranging from urticaria and angioedema to dyspnoea, hypotension, collapse, and shock. WDEIA usually develops after ingestion of wheat products followed by physical exercise. Other cofactors are acetylsalicylic acid and other non-steroidal anti-inflammatory drugs, alcohol, and infections. The precise mechanisms of WDEIA remain unclear; exercise and other cofactors might increase gastrointestinal allergen permeability and osmolality, redistribute blood flow, or lower the threshold for IgE-mediated mast cell degranulation. Among wheat proteins, ω5-gliadin and high-molecular-weight glutenin subunits have been reported to be the major allergens. In some patients, WDEIA has been discussed to be caused by epicutaneous sensitization with hydrolysed wheat gluten included in cosmetics. Diagnosis is made based on the patient's history in combination with allergy skin testing, determination of wheat-specific IgE serum antibodies, basophil activation test, histamine release test, and/or exercise challenge test. Acute treatment includes application of adrenaline or antihistamines. The most reliable prophylaxis of WDEIA is a gluten-free diet. In less severe cases, a strict limitation of wheat ingestion before exercise and avoidance of other cofactors may be sufficient., (© 2015 John Wiley & Sons Ltd.)

Celiac disease is an autoimmune systemic disease having among its clinical manifestations frequent symptoms common to rheumatologic diseases such as musculoskeletal pain, asthenia, and cognitive fatigue. It is associated with other autoimmune diseases like Sjögren disease. It is a well-characterized disease with specific diagnostic tests. Non-celiac gluten sensitivity is an emerging entity with symptoms similar to celiac disease, but without specific diagnostic tests. The concept of non-celiac gluten sensitivity and its diagnostic problems are reviewed, and the hypothesis of its association with fibromyalgia, spondyloarthritis, and autoimmune conditions is proposed. Clinical observations supporting the hypothesis are described, highlighting the benefit of treating non-celiac gluten sensitivity., (Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is increasing. In vitro test such as omega-5-gliadin levels are useful in the diagnosis, while oral single blind challenge tests (OCT) with wheat plus exercise continuous being the gold standard diagnostic method. This paper reports the case of a 38-year-old woman, with several episodes of anaphylaxis after eating different foods and doing exercise after ingestion. An allergy study was performed with positive skin prick tests for wheat, barley and rye. Total IgE 238.0KU/L, positive specific IgE (>100KU/L) to wheat, barley and rye, and negative to rTri-a-19 omega-5 gliadin. OCT with bread and exercise was positive. In this case of wheat-dependent exerciseinduced anaphylaxis (WDEIA) with negative serum specific IgE to omega-5-gliadin, negative results with gamma, alpha, bheta y omega-gliadin doesn't exclude the diagnosis of WDEIA.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, having a prevalence of 12%-30% in the general population. Most patients with IBS attribute their symptoms to adverse food reactions. We review the role of diet in the pathogenesis of IBS and the importance of dietary factors in the management of these patients. The MEDLINE electronic database (1966 to Jan 2015) was searched using the following keywords: "food", "diet", "food allergy", "food hypersensitivity", "food intolerance", "IBS", "epidemiology", "pathogenesis", "pathophysiology", "diagnosis", "treatment". We found 153 eligible papers; 80 were excluded because: not written in English, exclusive biochemical and experimental research, case reports, reviews, and research otherwise not relevant to our specific interest. We selected 73 papers: 43 original papers, 26 reviews and 4 letters to the editor. These papers focused on IBS pathogenesis, the association between IBS and atopy, and between IBS and food allergy, the relationship between IBS and non-celiac wheat sensitivity, the role of diet in IBS. Pending further scientific evidence, a cautious approach is advisable but the concept of food allergy should be included as a possible cause of IBS, and a dietary approach may have a place in the routine clinical management of IBS.

Remission of gastrointestinal and general symptoms after gluten withdrawal has been described in some non-celiac individuals for nearly 30 years. Only recently, efforts have been made to define this entity, now referred to as "non-celiac gluten sensitivity". It includes patients that clinically respond to gluten free diet without exhibiting allergic or autoimmune features to explain such response. Wheat allergy, celiac disease, irritable bowel syndrome and symptoms induced by high FODMAPs (Fermentable, Oligo-, Di-, Mono-saccharides And Polyols) consumption are the main differential diagnoses. The relationship with neuropsychiatric disorders such as schizophrenia and autism has not been demonstrated, but currently it gives ground to great hope in families with affected children. Epidemiology of non-celiac gluten sensitivity is not clear. It is described as more common among women and less common in children. Genetic and immune factors, changes in intestinal microbiota and non-gluten components present in wheat grains are main factors postulated in the pathogenesis of this condition. To date, there are no specific biomarkers for non-celiac gluten sensitivity and diagnosis is reached by excluding other causes of disease. A trial with gluten-free diet and subsequent gluten challenge is the methodology most frequently used to confirm diagnosis.

Background: Food allergy to lupine has frequently been reported in patients allergic to peanut or soy, and cross-reactivity between these legumes is known. Moreover, respiratory allergy to lupine has been described after inhalation, mostly at workplaces. Our aim was to study the frequency of lupine sensitization in European bakers with suspected bakers' allergy. Furthermore, associations between sensitizations to lupine and other plant allergens were investigated., Methods: One hundred and sixteen bakers with work-related allergic symptoms but without known food allergies were examined. Specific IgE (sIgE) antibodies to wheat flour, rye flour, lupine, peanut, soy and the recombinant single birch protein rBet v 1 were quantified. Selected sera were tested for cross-reactivity using ImmunoCAP inhibition and ISAC microarrays., Results: Whereas 67% of bakers were sensitized to wheat and/or rye flour, 35% showed sIgE to peanut and 33% to lupine. All lupine-positive bakers also had sIgE to either wheat flour (89%) and/or peanut (92%), and lupine sIgE correlated significantly with sIgE to peanut, soy, wheat and rye flour. Used as an inhibitor, wheat flour inhibited IgE binding to lupine in 4 out of 8 sera, indicating cross-reactivity. In microarrays, these sera showed IgE binding to lipid transfer proteins, profilins and/or cross-reactive carbohydrate determinants. Further inhibition experiments suggest that these single allergens are involved in cross-reactivity., Conclusion: One third of 116 symptomatic bakers showed sIgE to lupine. At least some of these sensitizations were based on cross-reactivity between lupine and wheat flour. However, the considerable sensitization rate could also be a sign that the use of lupine flour in bakeries may be of occupational relevance., (© 2015 S. Karger AG, Basel.)

Among grains and legumes, wheat and soybean are the most frequent and well-characterized allergenic foods. Wheat proteins are divided into water/salt-soluble and water/salt-insoluble (gluten) fractions. The most dominant allergen in the former is α-amylase/trypsin inhibitor, which acts as an inhaled allergen causing baker's asthma. Gluten allergens, including ω-5 gliadin and high- and low-molecular-weight glutenins, contribute to wheat-dependent exercise-induced anaphylaxis in adults and immediate-type wheat allergies, including anaphylaxis, in children. Recently, wheat allergies exclusively caused by hydrolyzed wheat proteins or deamidated glutens have been reported, and the presence of unique IgE-binding epitopes has been suggested. Soybean allergens contributing to immediate-type allergic reactions in children are present in seed storage proteins, namely Gly m 5, Gly m 6 and Gly m 8. However, pollen-related soybean allergy in adults is caused by the Bet v 1 homolog of soybeans, Gly m 4. Taken together, the varying clinical manifestations of wheat and soybean allergies are predominantly caused by their different allergen components., (© 2015 S. Karger AG, Basel.)

Background: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a specific form of wheat allergy caused by the combination of wheat ingestion and physical exercise and has been reported in other parts of Asia. At present, there are no published reports of WDEIA in Singapore. The objective of this study is to characterise the common local clinical and laboratory manifestations of WDEIA., Methods: This was a retrospective descriptive study of all WDEIA who presented to a tertiary Singaporean Hospital over a 5-year-period from 1 January 2009 to 30 June 2013., Results: Eight patients aged 9-41 years old were characterised. Six were males and the majority (5) was of Chinese ethnicity. An atopic history was found in four patients. The symptoms of anaphylaxis included cutaneous manifestations such as urticaria (n=7), angioedema (n=6), respiratory symptoms of dyspnoea and wheezing (n=5) and hypotension (n=5). The symptoms occurred 20-75 min after consumption of wheat-based products, often upon cessation of exercise [running (n=3), walking (n=4) and swimming (n=1)]. The WDEIA was recurrent in seven patients. The skin prick tests were positive to wheat in seven patients, and ω-5 gliadin test to wheat was positive in five patients., Conclusions: With the emergence of wheat allergy in East Asian countries, WDEIA has become an important condition for physicians and Singapore is no exception. Under-recognition combined with life-threatening symptoms warrants better public awareness measures. In addition, further studies are necessary to identify possible unique genetic and environmental exposures that could explain the inter-regional differences of WDEIA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The identification of a distinct syndrome, designated eosinophilic oesophagitis (EoE), with its own clinical and histopathological characteristics, was first described in the early 1990s. Meanwhile intense research has uncovered many molecular, immunological and clinical aspects of this chronic-inflammatory disorder. This article focuses exclusively on basic and clinical insights of EoE gathered during the last few years. Regarding aetiopathogenesis it has become clear that EoE is a food-triggered disease with milk and wheat as the dominant culprit food categories. However, it is still debated whether a disturbed mucosal integrity allowing allergens to cross the mucosal barrier, or changes in wheat and milk manufacturing might induce these inflammatory responses. Furthermore, basic science and clinical studies have accordingly confirmed that a chronic eosinophilic inflammation leads to a remodelling of the oesophagus with micro- and macro-morphological alterations, ending in a strictured oesophagus with impaired function. Fortunately, long-term therapeutic trials, using either topical corticosteroids or dietary allergen avoidance, have demonstrated that this sequela can be prevented or even reversed. This finding is of clinical relevance as it supports the initiation of a consistent anti-inflammatory therapy. Nevertheless, EoE is still an enigmatic disease and the long list of unanswered questions will certainly stimulate further research., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We report the case of a 73 year old man on chronic aspirin therapy who went in anaphylactic shock during his daily farm chores following a meal rich in wheat products. The serum specific IgE assay (ImmunoCAP) showed strong positive specific IgE responses to ω-5 gliadin. A two-year period avoiding wheat meals 3 hours prior to exercise, resulted in a lack of further anaphylaxis; this results aided us in making the diagnosis.

A 38-year-old woman was suffering from irregular headaches and sleepiness. She had used soap containing Glupearl 19S (hydrolyzed wheat proteins) every day for approximately one year and had experienced an episode of rash eruption on her face seven months ago. Wheat-specific IgE antibodies were detected in her serum. A Western blot analysis revealed a high titer of IgE antibodies against Glupearl 19S and wheat proteins. The patient was sensitive to these compounds in a skin prick test. After avoiding eating wheat, her headaches and sleepiness disappeared. A hidden food allergy is a possible cause of these symptoms.

Gluten-related disorders are a spectrum of systemic immune mediated conditions that occur at any age in genetically susceptible individuals upon ingesting gluten. Celiac disease and gluten sensitivity are the most important conditions of the spectrum. They may be associated with other autoimmune diseases, such as multiple sclerosis and neuromyelitis optica. Treatment with a gluten-free diet can provide considerable benefits to the patients having both a gluten-related disorder and one of these 2 demyelinating diseases of the central nervous system., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

Background: We performed an in vitro elicitation test to determine the ability of different types of wheat-allergic patients' IgE to induce humanized mast cell activation after the addition of various time-treated acid-hydrolyzed wheat proteins (HWPs)., Methods: The reactivity of heat- and various time-treated acid-hydrolyzed glutens (acid-HGs) and commercial acid-HWP (HWP1), using serum IgE from wheat allergy accompanied by skin and rhinoconjunctival sensitization to HWP1 in the facial soap, pediatric subjects with food allergy to native wheat, adult wheat-dependent exercise-induced anaphylaxis subjects, and nonatopic healthy subjects, was elucidated by dot blot and a luciferase assay-based in vitro elicitation test (EXiLE test)., Results: Serum from subjects sensitized with HWP1 reacted only to acid-HGs (acid-HGs treated for 0.5-3 or 6 h), but not native gluten, in the results of the dot blot. In contrast, sera from pediatric subjects sensitized with native wheat reacted to native gluten more strongly and showed only slight reactions to 0.5- to 1-hour-treated acid-HGs. The results of the in vitro elicitation test showed that acid hydrolyzation of the gluten attenuated antigen-induced luciferase expression in a time-dependent manner for sera from native-wheat-sensitized pediatric subjects. On the other hand, in the sera from HWP1-sensitized subjects, acid hydrolyzation of the gluten for 0.5 h dramatically increased luciferase expression., Conclusions: Even after prolonged hydrolyzation, acid-HGs still retained the ability to activate mast cells in the case of HWP1-sensitized subjects., (Copyright © 2012 S. Karger AG, Basel.)

Background: Exercise-induced anaphylaxis (EIA) is an under-recognized condition that is a distinct physical allergy. Triggers include varying amounts of exercise, alone or in combination with certain foods or medications (food-dependent EIA, or FDEIA). Therapy is identical to that of any immunoglobulin E-mediated allergic reaction., Objectives: This case is reported to increase awareness among emergency physicians of EIA and FDEIA., Case Report: A 57-year-old man was found with a diffuse erythematous rash after eating a wheat bagel and walking up five flights of stairs. Emergency medical services found him hypotensive and combative. In the Emergency Department, the patient's blood pressure was 72/27 mm Hg, with an oxygen saturation of 97% on non-rebreather mask. The physical examination was notable for bilateral inspiratory crackles in the lower one-third of the lungs. He received intravenous (i.v.) diphenhydramine 25 mg, i.v. methylprednisolone 125 mg, and 1 L of normal saline, after which his blood pressure improved to 110/54 mm Hg. He was admitted to the hospital where his recovery was uneventful., Conclusion: EIA and FDEIA are uncommon forms of physical allergy, but they represent important entities for emergency physicians to consider. Recognition of the association with exercise is key, as recurrences can be prevented by avoiding triggers., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A case of rice allergy in a patient with bakers asthma is described. On ISAC 112 IgE reactivity to wheat alpha-amylase/trypsin inhibitor (nTri a aA&#95;TI) and lipid tranfer protein (rTri a 14) was found. We hypothesize that the reaction by oral ingestion was elicited by homologous molecules in rice seeds.

Unlabelled: Few studies concerning the importance of wheat allergy affecting the course ofatopic eczema in adolescents and adult patients exist., Aim: The evaluation if wheat allergy can deteriorate the course of atopic eczema. Follow-up of patients with confirmed food allergy to wheat., Method: Altogether 179 persons suffering from atopic eczema were included in the study: 51 men and 128 women entered the study with an average age of 26.2 (s.d. 9.5 years) Dermatological and allergological examinations were performed, including skin prick tests, atopy patch tests, and specific serum IgE for wheat, open exposure test and double-blind, placebo-controlled food challenge test with wheat flour., Results: Wheat allergy affecting the coures of atopic eczema was confirmed in eight patients (4.5%) out of 179 patients enrolled in this study by double-blind, placebo controlled food challenge test. The course of atopic eczema showed a positive trend in patients with confirmed food allergy at 3, 6, 9, 12 month follow-up (statistical evaluation with paired t-test) after the elimination of wheat flour., Conclusion: Wheat allergy may play an important role in the worsening of atopic eczema (acting as a triggering exacerbating factor) only in a minority of adolescents and adult patients (4.5% in our study). The diagnostic methods (skin prick test, specific IgE, atopy patch test, history) cannot be used as separated tests for the determination of food allergy to wheat in patients with atopic eczema.Open exposure tests and double-blind, placebo-controlled food challenge should be used for the confirmation of wheat allergy affecting the course of atopic eczema.

A 70-year-old man with a history of food-dependent exercise-induced anaphylaxis (FDEIA) since age 50 was admitted to the emergency department with chest pain and urticaria caused by FDEIA. Coronary angiography revealed total occlusion of the proximal left anterior descending coronary artery. After thrombus aspiration, a bare metal stent was placed into the culprit lesion, resulting in no residual stenosis. Urticaria disappeared on the second hospital day. This is the first reported case, to our knowledge, in which acute myocardial infarction followed FDEIA. Physicians should be aware of acute myocardial infarction as a rare but potential complication of FDEIA.