Food allergy in irritable bowel syndrome:The case of non-celiac wheat sensitivity

Irritable bowel syndrome(IBS) is one of the most common gastrointestinal disorders, having a prevalence of 12%-30% in the general population. Most patientswith 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.

Non-celiac gluten sensitivity:Time for sifting the grain

In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism(autoimmune in celiac disease and Ig E-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity(NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined.

Non-celiac gluten sensitivity: All wheat attack is not celiac

Currently,1% of the United States population holds a diagnosis for celiac disease(CD),however,a more recently recognized and possibly related condition,"non-celiac gluten sensitivity"(NCGS)has been suggested to affect up to 6%of the United States public.While reliable clinical tests for CD exist,diagnosing individuals affected by NCGS is still complicated by the lack of reliable biomarkers and reliance upon a broad set of intestinal and extra intestinal symptoms possibly provoked by gluten.NCGS has been proposed to exhibit an innate immune response activated by gluten and several other wheat proteins.At present,an enormous food industry has developed to supply gluten-free products(GFP)with GFP sales in 2014 approaching$1 billion,with estimations projecting sales to reach$2 billion in the year 2020.The enormous demand for GFP also reflects a popular misconception among consumers that gluten avoidance is part of a healthy lifestyle choice.Features of NCGS and other gluten related disorders(e.g.,irritable bowel syndrome)call for a review of current distinctive diagnostic criteria that distinguish each,and identification of biomarkers selective or specific for NCGS.The aim of this paper is to review our current understanding of NCGS,highlighting the remaining challenges and questions which may improve its diagnosis and treatment.

Extra-intestinal manifestations of non-celiac gluten sensitivity: an expanding paradigm

Non celiac gluten sensitivity(NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease(CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as ‘foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders(irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal NCGS manifestations could be supported by evidence-based agreements.

Non-celiac gluten sensitivity： questions still to be answered despite increasing awareness

Recently, the increasing number of patients worldwide who are sensitive to dietary gluten without evidence of celiac disease or wheat allergy has contributed to the identification of a new gluten-related syndrome defined as non-celiac gluten sensitivity. Our knowledge regarding this syndrome is still lacking, and many aspects of this syndrome remain unknown. Its pathogenesis is heterogeneous, with a recognized pivotal role for innate immunity; many other factors also contribute, inctuding tow-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Gluten and other wheat proteins, such as amylase trypsin inhibitors, are the primary triggers of this syndrome, but it has also been hypothesized that a diet rich in fermentable monosaccharides and polyols may elicit its functional gastrointestinal symptoms. The epidemiology of this condition is far from established; its prevalence in the general population is highly variable, ranging from 0.63% to 6%. From a clinical point of view, non-celiac gluten sensitivity is characterized by a wide array of gastrointestinal and extraintestinal symptoms that occur shortly after the ingestion of gluten and improve or disappear when gluten is withdrawn from the diet. These symptoms recur when gluten is reintroduced. Because diagnostic biomarkers have not yet been identified, a double-blind placebo-controlled gluten challenge is currently the diagnostic method with the highest accuracy. Future research is needed to generate more knowledge regarding non-celiac gluten sensitivity, a condition that has global acceptance but has only a few certainties and many unresolved issues.

Clinical and diagnostic aspects of gluten related disorders

Gluten is one of the most abundant and widely distributed components of food in many areas. It can be included in wheat, barley, rye, and grains such as oats, barley, spelt, kamut, and triticale. Gluten-containinggrains are widely consumed; in particular, wheat is one of the world's primary sources of food, providing up to 50% of the caloric intake in both industrialized and developing countries. Until two decades ago, celiac disease(CD) and other gluten-related disorders were believed to be exceedingly rare outside of Europe and were relatively ignored by health professionals and the global media. In recent years, however, the discovery of important diagnostic and pathogenic milestones led CD from obscurity to global prominence. In addition, interestingly, people feeding themselves with glutenfree products greatly outnumber patients affected by CD, fuelling a global consumption of gluten-free foods with approximately $2.5 billion in United States sales each year. The acknowledgment of other medical conditions related to gluten that has arisen as health problems, providing a wide spectrum of gluten-related disorders. In February 2011, a new nomenclature for gluten-related disorders was created at a consensus conference in London. In this review, we analyse innovations in the field of research that emerged after the creation of the new classification, with particular attention to the new European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for CD and the most recent research about non-celiac gluten sensitivity.

Microscopic enteritis:Bucharest consensus

Microscopic enteritis(ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms,nutrient and micronutrient deficiency.It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy.This work recognises a need to characterize disorders with microscopic and submicroscopic features,currently regarded as functional or non-specific entities,to obtain further understanding of their clinical relevance.The consensus working party reviewed statements about the aetiology,diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment.Following the 5th International Course in Digestive Pathology in Bucharest in November 2012,an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME.A five-step agreement scale(from strong agreement to strong disagreement) was used to score 21 statements,independently.There was strong agreement on all statements about ME histology(95%-100%).Statements concerning diagnosis achieved 85% to 100% agreement.A statement on the management of ME elicited agreement from the lowest rate(60%) up to 100%.The remaining two categories showed general agreement between experts on clinical presentation(75%-95%) and pathogenesis(80%-90%) of ME.There was strong agreement on the histological definition of ME.Weaker agreement on management indicates a need for further investigations,better definitions and clinical trials to produce quality guidelines for management.This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

Role of capsule endoscopy in suspected celiac disease: A European multi-centre study

AIMTo analyze the diagnostic yield (DY), therapeutic impact (TI) and safety of capsule endoscopy (CE).METHODSThis is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease (CD) (mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy (Group-I, n = 19), seropositive CD without atrophy (Group-II, n = 39), contraindication to gastroscopy (Group-III, n = 6), seronegative CD without atrophy, but with a compatible context (Group-IV, n = 99). DY, TI and the safety of CE were analysed.RESULTSThe overall DY was 54% and the final diagnosis was villous atrophy (n = 65, 39.9%), complicated CD (n = 12, 7.4%) and other enteropathies (n = 11, 6.8%; 8 Crohn’s). DY for groups I to IV was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases (36.9%), diffuse in 19 (29.2%), jejunal in 11 (16.9%), and patchy in 10 cases (15.4%). Factors associated with a greater DY were positive serology (68.3% vs 49.2%, P = 0.034) and older age (P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE results changed the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI (92.3% vs 45.3%, P < 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention (0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD.CONCLUSIONCE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD.

小麦麸质蛋白相关性疾病的研究进展

小麦是主要的粮食作物,但也可引发多种过敏性疾病和自身免疫性疾病。麸质蛋白的摄入,是引起这些疾病的关键因素,麸质蛋白主要存在于小麦中,但也存在于大麦,黑麦和燕麦中。特别是小麦麸质蛋白因含有大量的非极性氨基酸和谷氨酰胺而耐胃肠道酶消化,生成使部分人群致病的毒性肽。麸质蛋白相关性疾病的全球患病率接近5%,已经严重影响了部分人群的生活质量,甚至危及生命,已成为全球性不可回避的食品安全问题之一。本文主要对麸质蛋白结构、麸质蛋白相关性疾病的发病机制、流行病学、诊断和治疗进行了概述,为小麦的安全食用提供参考。

Hepatitis B vaccine in celiac disease:Yesterday,today and tomorrow

Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV).The non-responsiveness to HBV vaccine has also been described in healthy people,nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls.Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described,such as the genetic hypothesis,according with CD patients carrying the disease-specific haplotype HLA-B8,DR3,and DQ2,show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype.On the other hand,it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine.Moreover,it has been demonstrated a possible genetic predisposition to hepatitis B vaccine nonresponsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokinereceptors and toll like receptors,but the pathogenic mechanism responsible for this low responsiveness still remains unclear.The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients.

Non-dietary forms of treatment for adult celiac disease

At present,treatment for celiac disease includes a strict gluten-free diet.Compliance,however,is difficult and gluten-free food products are costly,and,sometimes very inconvenient.A number of potential alternative measures have been proposed to either replace or supplement gluten-free diet therapy.In the past,non-dietary forms of treatment were used(e.g.,corticosteroids) by some clinicians,often to supplement a gluten-free diet in patients that appeared to be poorly responsive to a gluten-free diet.Some of new and novel non-dietary measures have already advanced to a clinical trial phase.There are still some difficulties even if initial studies suggest a particularly exciting and novel form of non-dietary treatment.In particular,precise monitoring of the response to these agents will become critical.Symptom or laboratory improvement may be important,but it will be critical to ensure that ongoing inflammatory change and mucosal injury are not present.Therapeutic trials will be made more difficult because there is already an effective treatment regimen.

The Impact of Gluten-Free Diet on Hormonal Balance

This study investigated how a gluten-free diet affects hormones, with particular emphasis on cortisol, thyroid, insulin, and sex hormones. Background: For medical diseases such as non-celiac gluten sensitivity, wheat allergy, and celiac disease, a gluten-free diet is important. The main area of concern for research is how a gluten-free diet can affect hormone levels and related health consequences. A review of the body of research on this topic, including studies on hormone regulation and the impact of dietary modifications, is a part of the methodology. These findings imply that a gluten-free diet may have an impact on hormone levels, which may affect metabolism, weight, and general health. These implications include the need for additional studies, particularly in those with autoimmune illnesses, to completely comprehend the relationship between a gluten-free diet and hormone regulation.

大咯血介入治疗失败的罕见原因:腹腔动脉系统参与供血(附2例报告及文献复习)

目的:咯血的主要责任血管是支气管动脉,非支气管性体动脉参与供血是大咯血介入治疗失败的重要原因,腹腔动脉系统分支动脉参与供血更为罕见。本文通过收集相关病例,结合国内外相关研究,提高对腹腔动脉系统分支动脉为咯血责任动脉的认识,探讨其可能的病理机制、危险因素。方法:回顾分析2例腹腔动脉系统分支(胃左动脉、肝左动脉)参与大咯血供血动脉的临床及影像学资料,并报道介入栓塞治疗的效果。结果:2例患者均为支气管动脉栓塞后再发大咯血,再次血管造影显示1例肝左动脉参与供血,1例胃左动脉参与供血。栓塞上述血管后,患者止血成功。病变位于下肺、伴有胸膜增厚,提示有腹腔动脉系统分支动脉参与供血的可能。术前仔细阅读患者影像学资料,术前行主动脉分支动脉CT血管成像,可减少对责任性非支气管性体动脉的遗漏。结论:腹腔动脉系统参与供血是介入栓塞治疗后咯血复发的少见原因,了解其病理机制、危险因素,及时进行栓塞,可以降低咯血的复发率。