Celiac Disease and Sensitization to Wheat, Rye, and Barley: Should We Be Concerned?

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.

Food-induced anaphylaxis in infancy compared to preschool age: A retrospective analysis.

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.

Wheat Intolerance and Chronic Gastrointestinal Symptoms in an Australian Population-based Study: Association Between Wheat Sensitivity, Celiac Disease and Functional Gastrointestinal Disorders.

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.

Grass-Allergic Children Frequently Show Asymptomatic Low-Level IgE Co-Sensitization and Cross-Reactivity to Wheat.

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.

Is perceived intolerance to milk and wheat associated with the corresponding IgG and IgA food antibodies? A cross sectional study in subjects with morbid obesity and gastrointestinal symptoms.

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/m2 or ≥35 kg/m2 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.

Wheat-dependent exercise-induced anaphylaxis.

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.

Wheat protein recognition pattern in tolerant and allergic children.

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.

INCIDENCE OF APNEA ATTACK AS ALLERGIC REACTION AFTER ORAL FOOD CHALLENGE IN PATIENT WITH IgE-MEDIATED WHEAT ALLERGY.

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.

IgE sensitization to lupine in bakers - cross-reactivity or co-sensitization to wheat flour?

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.

[Non-celiac gluten sensitivity: Another condition that responds to gluten]. / Sensibilidad no celíaca al gluten: Una patología más que responde al gluten.

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.

Update on basic and clinical aspects of eosinophilic oesophagitis.

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.

Wheat-dependent exercise-induced anaphylaxis: a retrospective case review from a tertiary hospital.

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.

Exercise-induced anaphylaxis in a cardiopathic patient on chronic aspirin therapy.

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.

Evaluation of allergenicity of acid-hydrolyzed wheat protein using an in vitro elicitation test.

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.

Exercise-induced anaphylaxis as a cause of syncope.

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.

A case of rice allergy in a patient with baker's asthma.

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_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.

The effect of wheat allergy on the course of atopic eczema in patients over 14 years of age.

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.