Nonallergic Diseases Associated With Foods.

Clinicians are faced with evaluating real and alleged reactions to foods that may be allergic or nonallergic. Pathogenesis, diagnosis, and treatment of various non-IgE-mediated diseases are discussed in this review. These food-related conditions range from mild to severe. Referral for an allergy workup may be pursued despite the lack of IgE-mediated symptoms. Diagnostic testing is available for defined non-IgE-mediated food diseases that are either immunologic or nonimmunologic. These include celiac disease and related disorders, carbohydrate maldigestion, pancreatic insufficiency, and histamine intolerance. In contrast, there is a paucity of definitive studies to prove food intolerance diseases. There are no definitive diagnostic criteria or testing for nonceliac gluten sensitivity. Functional gastrointestinal disorders, such as irritable bowel syndrome, are better stratified diagnostically but still lack reliable testing. Both nonceliac gluten sensitivity and irritable bowel syndrome are linked to dietary triggers including fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. Therefore, dietary alteration alone may be diagnostic and therapeutic when all other conditions are ruled out. These conditions are important considerations when evaluating a patient with history of a food reaction. There is little evidence that foods are causative in other ailments such as acne, migraines, and nasal congestion and hypersecretion.

Gluten Sensitivity Underlying Resistant "Laryngopharyngeal Reflux" Symptoms and Signs.

INTRODUCTION: Laryngopharyngeal reflux (LPR) is one of the most common conditions encountered in otolaryngology. Gluten sensitivity may mimic the signs and symptoms of LPR or act as an aggravating cofactor with LPR. Gluten sensitivity and food intolerance also have been implicated as conditions that may be associated specifically with LPR symptoms and signs resistant to traditional medical treatment. Medical management of LPR may be insufficient to control symptoms and laryngeal signs of reflux, constituting resistant LPR. Eliminating gluten from the diet could provide symptomatic relief to patients with gluten sensitivity and LPR that is not controlled adequately by current regimens. The purpose of our study was to investigate the relationship between gluten sensitivity and LPR. We aimed to evaluate reflux finding score (RFS) improvement following elimination of gluten from the diet in patients with resistant LPR who had positive blood tests associated with gluten sensitivity. Symptom improvement was also assessed following dietary gluten elimination. Lastly, we aimed to identify predictors for a positive response to a gluten-free diet. METHODS: Adult patients who underwent gluten sensitivity testing for treatment-resistant LPR symptoms and/or signs were included. Patients with ≥1 positive test were advised to begin a therapeutic trial of a gluten-free diet. Subjects who chose not to trial a gluten-free diet or tested negative for gluten sensitivity markers served as controls. RFS was the primary outcome measure. RESULTS: One hundred ninety-seven patients were included; 81 trialed a gluten-free diet. Subjects who trialed the gluten-free diet were significantly more likely to demonstrate objective improvement in RFS (77.14% vs 43.88%), and report subjective improvement (55.41% vs 25.77%) than those who did not. RFS had decreased significantly from baseline at 1-3, 3-6, 6-12, and >12-month interval follow-up examinations in subjects who trialed a gluten-free diet. Comparison between subjects who trialed the gluten-free diet, tested positive for a gluten sensitivity marker but did not trial the gluten-free diet, and subjects who were negative for all gluten sensitivity markers revealed that a gluten-free diet was associated with a significantly greater percent improvement in RFS compared to controls at 1-3, 6-12, and >12-months. CONCLUSION: Gluten sensitivity can mimic or aggravate LPR. A gluten-free diet should be considered for patients with resistant LPR, especially if blood test abnormalities that suggest gluten sensitivity are identified. The diet should be maintained for a minimum of three months to demonstrate objective improvement using RFS.

Gluten, Inflammation, and Neurodegeneration.

Growing evidence supports a potential link between dietary gluten intake and neurodegenerative disease in susceptible populations. Observational data supporting this link are described along with interventional study data evaluating the effects of restricting gluten from the diet in patients with neurologic disorders. Suggested underlying mechanisms between gluten intake and neurodegeneration are discussed.

[Dermatitis herpetiformis and other forms of wheat sensitivity]. / Dermatitis herpetiformis und sonstige Formen der Weizensensitivität.

BACKGROUND: Wheat sensitivity is a collective term for several, especially gastrointestinal, diseases that occur as part of a hypersensitivity reaction after wheat consumption. The symptoms, which are mostly similar to those of irritable bowel syndrome, are often accompanied by skin lesions. In addition to celiac disease and dermatitis herpetiformis, the cutaneous manifestation of celiac disease, wheat sensitivity also includes nonceliac gluten sensitivity (NCGS), allergic nickel contact mucositis, wheat allergy, amylase-trypsin inhibitor intolerance, and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) intolerance. OBJECTIVES: This review article aims to provide an overview of the clinical, especially dermatological and gastrointestinal features of the different forms of wheat sensitivity. Diagnosis and therapeutic management are also discussed. MATERIALS AND METHODS: A selective literature search was carried out with evaluation of our own clinical data. RESULTS: The skin lesions in dermatitis herpetiformis are very disease-specific. In contrast, wheat allergy often shares signs and symptoms with many other diseases. Other forms of wheat sensitivity cause primarily gastrointestinal abnormalities, but extra-intestinal manifestations can also occur. Their diagnosis is often complex and requires cross-disciplinary collaboration with experts in gastroenterology. The therapy consists of a wheat- or gluten-free diet. CONCLUSIONS: Knowledge of the different and frequently occurring dermatological signs of wheat sensitivity is of great importance, because dermatological manifestations associated with gastrointestinal pathology, intolerance reactions, and allergies appear more and more frequently.

Food Allergies and Intolerances: A Clinical Approach to the Diagnosis and Management of Adverse Reactions to Food.

Food allergy is an aberrant immunological response to food antigen, which can result in potentially life-threatening reactions. It is often challenging to differentiate food allergy from other adverse reactions to food because their presentations can be indistinguishable. The purpose of this article is to give an overview of the classification, evaluation, and management of adverse food reactions, key differentiating features of food allergy, roles and limitations of various food allergy testing, and promising areas of emerging research. Case studies are used to highlight some of the clinical pearls in diagnosing and managing food-related diseases.

[Non-celiac Gluten Sensitivity].

Non-celiac gluten sensitivity (NCGS) is a term that is used to describe individuals who are not affected by celiac disease or wheat allergy, yet they have intestinal and/or extra-intestinal symptoms related to gluten ingestion with improvement of their symptoms upon withdrawing gluten from their diet. Gluten-related disorder groups are manifested by symptoms of gastrointestinal tract disorders, as well as hematological dermatological endocrinological, gynecological, rheumatological and nervous system symptoms. It is believed that NCGS represents heterogeneous groups with different subgroups characterized by different etiologies, clinical histories and clinical courses. There also appears to be an overlap between NCGS and irritable bowel syndrome (IBS). There is a need for establishing strict criteria for diagnosing NCGS. The absence of validated biomarkers remains a significant limitation for research studies on NCGS. New evidence shows that a gluten-free diet may be beneficial for some patients with gastrointestinal symptoms, such as those symptoms commonly found in patients with IBS. Further studies about NCGS are needed.

Non-celiac Gluten Sensitivity / 대한소화기학회지

Non-celiac gluten sensitivity (NCGS) is a term that is used to describe individuals who are not affected by celiac disease or wheat allergy, yet they have intestinal and/or extra-intestinal symptoms related to gluten ingestion with improvement of their symptoms upon withdrawing gluten from their diet. Gluten-related disorder groups are manifested by symptoms of gastrointestinal tract disorders, as well as hematological dermatological endocrinological, gynecological, rheumatological and nervous system symptoms. It is believed that NCGS represents heterogeneous groups with different subgroups characterized by different etiologies, clinical histories and clinical courses. There also appears to be an overlap between NCGS and irritable bowel syndrome (IBS). There is a need for establishing strict criteria for diagnosing NCGS. The absence of validated biomarkers remains a significant limitation for research studies on NCGS. New evidence shows that a gluten-free diet may be beneficial for some patients with gastrointestinal symptoms, such as those symptoms commonly found in patients with IBS. Further studies about NCGS are needed.

Who Should Be Gluten-Free? A Review for the General Practitioner.

Historically, a gluten-free diet was recommended only for those with celiac disease or IgE-mediated wheat allergy. With changes in food allergy labeling in the United States and the publication of several best-selling books, gluten-related disorders have come to the forefront of popular culture. As a result, there has been a dramatic increase in the number of gluten-free diet followers, many for nontraditional reasons. As "going gluten-free" has become mainstream, it is imperative that health care providers acquire the knowledge to identify true gluten-related disorders to effectively counsel their patients and minimize potential complications from following such a restrictive diet.

Targeted LC-MS/MS Reveals Similar Contents of α-Amylase/Trypsin-Inhibitors as Putative Triggers of Nonceliac Gluten Sensitivity in All Wheat Species except Einkorn.

Amylase/trypsin-inhibitors (ATIs) are putative triggers of nonceliac gluten sensitivity, but contents of ATIs in different wheat species were not available. Therefore, the predominant ATIs 0.19 + 0.53, 0.28, CM2, CM3, and CM16 in eight cultivars each of common wheat, durum wheat, spelt, emmer, and einkorn grown under the same environmental conditions were quantitated by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) and stable isotope dilution assays using specific marker peptides as internal standards. The results were compared to a label-free untargeted LC-MS/MS analysis, in which protein concentrations were determined by intensity based absolute quantitation. Both approaches yielded similar results. Spelt and emmer had higher ATI contents than common wheat, with durum wheat in between. Only three of eight einkorn cultivars contained ATIs in very low concentrations. The distribution of ATI types was characteristic for hexaploid, tetraploid, and diploid wheat species and suitable as species-specific fingerprint. The results point to a better tolerability of einkorn for NCGS patients, because of very low total ATI contents.

Health Benefits and Adverse Effects of a Gluten-Free Diet in Non-Celiac Disease Patients.

Gluten-related diseases such as celiac disease and gluten ataxia are rare conditions, affecting less than 1% of the population in the United States. Despite the rarity of these diseases, there have been significant increases in the adoption of a gluten-free lifestyle and the consumption of gluten-free foods in the United States over the last 3 decades. More than $15.5 billion were spent on retail sales of gluten-free foods in 2016. The gluten-free diet is driven by multiple factors, including social and traditional media coverage, aggressive consumer-directed marketing by manufacturers and retail outlets, and reports in the medical literature and mainstream press of the clinical benefits of gluten avoidance. Individuals may restrict gluten from their diets for a variety of reasons, such as improvement of gastrointestinal and nongastrointestinal symptoms, as well as a perception that gluten is potentially harmful and, thus, restriction represents a healthy lifestyle. Emerging evidence shows that gluten avoidance may be beneficial for some patients with gastrointestinal symptoms, such as those commonly encountered with irritable bowel syndrome. However, high-quality evidence supporting gluten avoidance for physical symptoms or diseases other than those specifically known to be caused by immune-mediated responses to gluten is neither robust nor convincing. In fact, gluten avoidance may be associated with adverse effects in patients without proven gluten-related diseases. This article provides insight regarding gluten avoidance patterns and effects on patients without gluten-related diseases, and highlights concerns surrounding gluten avoidance in the absence of a gluten-mediated immunologic disease.

Nutritional Consideration in Celiac Disease and Nonceliac Gluten Sensitivity.

Celiac disease is an autoimmune disorder due to the inflammatory response to gluten in genetically predisposed individuals. It causes an enteropathy associated with several nutritional complications. Strict compliance to a gluten-free diet (GFD) is the current primary therapy. Nonceliac gluten sensitivity (NCGS) is a condition in which gluten ingestion leads to systemic symptoms but is not associated with small bowel atrophy or abnormal celiac serologies. A GFD heals celiac disease enteropathy and improves symptoms in NCGS. However, a long-term GFD can be associated with nutritional deficiencies and requires monitoring and guidance.

The 5 Ws of a gluten challenge for gluten-related disorders.

Gluten-related disorders (GRDs) are gradually emerging as epidemiologically relevant diseases, with a global prevalence estimated to be approximately 5% in the population. Conditions related to gluten ingestion include celiac disease (CD), wheat allergy (WA), and nonceliac gluten sensitivity (NCGS). Although mediated by different pathogenic pathways, these 3 conditions share similar clinical manifestations and can present a difficult differential diagnosis. The gluten challenge (GC) is an important diagnostic tool for GRDs, but there is great variability in regards to deciding which patients should be challenged, what amount of gluten should be used, what the GC duration should be, when and where the GC should occur, and, sometimes, why to conduct a GC. This review summarizes the current knowledge about the desirable characteristics of GCs in the 3 main GRDs following a 5 Ws approach-that is, the 5 main journalistic questions: who, what, when, where, why. The answers will help to determine the correct use of the GC in diagnosing GRDs.

Gluten sensitivities and the allergist: Threshing the grain from the husks.

"Gluten sensitivity" has become commonplace among the public. Wheat allergy (WA) and celiac disease (CD) are well-defined entities, but are becoming a fraction of individuals following a gluten-free diet (GFD). Wheat allergy has a prevalence of <0.5%. Wheat, specifically its omega-5 gliadin fraction, is the most common allergen implicated in food-dependent, exercise-induced anaphylaxis. CD is a non-IgE hypersensitivity to certain cereal proteins: gluten in wheat, secalin in rye, hordein in barley, and to a lesser extent avenin in oat. It is a rare disease, with an estimated prevalence that varied widely geographically, being higher in Northern Europe and the African Saharawi region than in South-East Asia. In addition to suggestive symptoms, serologic testing has high diagnostic reliability and biopsy is a confirmatory procedure. Patients with CD have extra-intestinal autoimmune comorbid conditions more frequently than expected. A third entity is nonceliac gluten sensitivity, which has been created because of the increasing number of subjects who claim a better quality of life or improvement of their variety of symptoms on switching to a GFD. The phenomenon is being fueled by the media and exploited by the industry. The lack of a specific objective test has been raising substantial controversy about this entity. Allergists and gastroenterologists need to pay attention to the multitudes of individuals who elect to follow a GFD. Many such subjects might have WA, CD, or another illness. Providing them with appropriate evaluation and specific management would be of great advantages, medically and economically.

Celiac Disease and Nonceliac Gluten Sensitivity.

Gluten-related disorders include celiac disease (CD), wheat allergy, and nonceliac gluten sensitivity. CD is an autoimmune enteropathy caused by damage to small intestinal mucosa when gluten is ingested in genetically susceptible individuals. Currently, the only available treatment of CD is gluten-free diet. Several potential treatments are being researched. Wheat allergy is a hypersensitivity reaction caused by IgE-mediated and/or non-IgE-mediated immune response, and can involve the gastrointestinal tract, skin, or respiratory tract. Nonceliac gluten sensitivity is one of a variety of immunologic, morphologic, or symptomatic manifestations precipitated by ingestion of gluten in individuals in whom CD and wheat allergy are excluded.

Small Amounts of Gluten in Subjects With Suspected Nonceliac Gluten Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.

BACKGROUND & AIMS: There is debate over the existence of nonceliac gluten sensitivity (NCGS) intestinal and extraintestinal symptoms in response to ingestion of gluten-containing foods by people without celiac disease or wheat allergy. We performed a randomized, double-blind, placebo-controlled, cross-over trial to determine the effects of administration of low doses of gluten to subjects with suspected NCGS. METHODS: We enrolled 61 adults without celiac disease or a wheat allergy who believed ingestion of gluten-containing food to be the cause of their intestinal and extraintestinal symptoms. Participants were assigned randomly to groups given either 4.375 g/day gluten or rice starch (placebo) for 1 week, each via gastrosoluble capsules. After a 1-week gluten-free diet, participants crossed over to the other group. The primary outcome was the change in overall (intestinal and extraintestinal) symptoms, determined by established scoring systems, between gluten and placebo intake. A secondary outcome was the change in individual symptom scores between gluten vs placebo. RESULTS: According to the per-protocol analysis of data from the 59 patients who completed the trial, intake of gluten significantly increased overall symptoms compared with placebo (P = .034). Abdominal bloating (P = .040) and pain (P = .047), among the intestinal symptoms, and foggy mind (P = .019), depression (P = .020), and aphthous stomatitis (P = .025), among the extraintestinal symptoms, were significantly more severe when subjects received gluten than placebo. CONCLUSIONS: In a cross-over trial of subjects with suspected NCGS, the severity of overall symptoms increased significantly during 1 week of intake of small amounts of gluten, compared with placebo. Clinical trial no: ISRCTN72857280.

A Clinical Update: Nonceliac Gluten Sensitivity-Is It Really the Gluten?

Gluten-free diets are increasing in popularity among consumers and fueling a global market of gluten-free products. A gluten-free diet is the only treatment for celiac disease (CD). However, many patients are self-reporting and suspecting "gluten sensitivity" after gastrointestinal symptoms, such as bloating, abdominal pain, or diarrhea, resolve on a gluten-free diet without formal evaluation testing for food allergies or CD. The terms related to gluten and/or wheat intolerance, nonceliac gluten sensitivity or wheat sensitivity, CD, and wheat allergy can be confusing. These forms of intolerance combined affect approximately 10% of the United States population. In this article we clarify the range of gluten and/or wheat disorders, clinical features, diagnosis, and management.