Nonceliac wheat sensitivity in the context of multiple food hypersensitivity: new data from confocal endomicroscopy.

Dear Editor, We enjoyed reading the article by Fritscher-Ravens et al who showed, by confocal endomicroscopy, that candidate food antigens caused immediate duodenal mucosa damage in irritable bowel syndrome (IBS) patients with a prolonged clinical history of symptoms after meals. Their in vivo data add evidence to the relationship between IBS and food allergy and seem to reinforce our hypothesis that a percentage of “nonceliac wheat sensitive” (NCWS) -patients with an IBS-like clinical presentation could suffer from non-immunoglobulin E-mediated wheat allergy. However, we would suggest that the very high percentage of positive confocal laser endomicroscopy patients (CLE) -22 out of 36- found in the study of Fritscher-Ravens et al could depend on their inclusion criteria (refractory daily symptoms >1 year, daily shortly after meal symptoms); in our experience, the frequency of food hypersensitivity diagnosed by double-blind, placebo-controlled (DBPC) food challenges in IBS is slightly <30% (276 patients out of 920). Apart from the epidemiologic data, which were not the objectives of this pilot study, we would like to underline some aspects of the study and make some suggestions for future research. It is interesting that a total of 32 reactions were analyzed, with different food antigens, in 22 CLE-positive patients and that the second most frequently offending food, after wheat, was cow’s milk. This is in keeping with our data about the high frequency of multiple food hypersensitivities in patients with NCWS. We showed that 206 of 276 NCWS subjects also became symptomatic after DBPC cow’s milk proteins challenge. These observations should induce the physicians who suspect a relationship between NCWS or food hypersensitivity and IBS to suggest an elimination diet with the exclusion of more food rather than just wheat, and that the reintroduction should be performed singly and with great caution, as described. In fact, a lack of response to a wheat-free diet could depend on hypersensitivity to other food antigens which are still included in the patients’ diet. We found also of great interest that CLE showed significantly higher intraepithelial lymphocyte (IEL) count in CLE positive than CLE-negative patients and in controls. Furthermore, histology showed that the mean values of IEL in CLE-positive patients were 26.4 ± 2.7 per 100 cells. Overall, this could indicate a state of mucosal inflammation owing to food hypersensitivity. A previous NCWS study which excluded patients with >25 IEL per 100 EC in the duodenal mucosa, very probably missed the group of NCWS patients who had an immunologic pathogenesis at the basis of their troubles. However, in our opinion, NCWS is a heterogeneous condition, which includes different subgroups of patients and the “allergic hypothesis” does not exclude that, in other NCWS patients, wheat amylase trypsin inhibitors or fermentable sugars4 could be the main pathogenetic triggers. Finally, we think that the authors showed that CLE is an excellent instrument to demonstrate food-related reactions in IBS and to separate a subgroup of the NCWS -those with non-immunoglobulin E-mediated wheat hypersensitivity- from the confuse melting pot that NCWS still is. However, awaiting a wider diffusion of this endoscopic means, and taking into account that the economic resources are decreasing in developed countries, it would be very important to correlate the CLE finding with simpler, noninvasive biomarkers. In this respect, it would be interesting to know whether CLE findings correlate with the eosinophil cationic protein concentrations in the stools or with the flow cytometric allergen stimulation assay results, biomarkers that showed a good concordance with the DBPC challenge results in IBS patients

Immunology of human rickettsial diseases.

Among human rickettsial diseases caused by micro-organisms of the genus Rickettsia (Order Rickettsiales; Family Rickettsiaceae), transmitted to human hosts through arthropod vectors, Mediterranean Spotted Fever, or Boutonneuse Fever, and Rocky Mountain Spotted Fever are considered to be important infectious diseases due to continued prevalence in the developed world, and potentially fatal outcome in severe cases. Proliferation of rickettsiae, at the site of the tick bite, results in focal epidermal and dermal necrosis (tache noire). Rickettsiae then spread via lymphatic vessels to the regional lymph nodes, and, via the bloodstream, to skin, brain, lungs, heart, liver, spleen and kidneys. The pathogen invades and proliferates in the endothelial cells of small vessels, target cells of rickettsial infection, destroying them, and spreading the infection to the endothelia of the vascular tree. The damage of the endothelium, and the subsequent endothelia dysfunction, is followed by the activation of acute phase responses, with alteration in the coagulation and in the cytokine network, together with a transient immune dysregulation, characterized by the reduction in peripheral CD4+ T lymphocytes

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 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

From Food Map to FODMAP in Irritable Bowel Sindrome.

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diseases in the general population, with a prevalence ranging from 12 % to 30 %, mainly affecting younger patients (i.e., <50 years of age) and women [1]. As in other chronic functional gastrointestinal disorders, abdominal discomfort or pain, abnormal bowel habits, and often bloating and abdominal distension are the main clinical features. Their diagnosis is based on symptom patterns (i.e., the Rome III criteria), which also allow categorization in diarrhea-predominant (D-IBS), constipation-predominant (C-IBS), mixed diarrhea and constipation (M-IBS), and unclassified (U-IBS) IBS [2]. Symptom severity ranges from tolerable to severe, both between different patients and in the same patient, affecting patients’ quality of life considerably as in some major chronic diseases [3]. Depending on whether diarrhea or constipation is the predominant disorder, antispasmodics, antidepressants, and medications modifying bowel habit represent the main conventional IBS treatments. Unfortunately, most patients report long-term inadequacy of current drug therapy and a tendency to seek a variety of alternative remedies, especially of a dietary nature (up to 65 % of them attribute their symptoms to adverse food reactions) [4]. However, the relationship between IBS symptoms and diet is still controversial, because of research quality and low number of scientific studies [5]. This represents a glaring gap that needs to be addressed

Role of FODMAPs in Patients With Irritable Bowel Syndrome: A Review.

Irritable bowel syndrome (IBS) is a condition characterized by abdominal pain, bloating, flatus, and altered bowel habits. The role of dietary components in inducing IBS symptoms is difficult to explore. To date, foods are not considered a cause but rather symptom-triggering factors. Particular interest has been given to the so-called FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols). We aimed to summarize the evidence from the most common approaches to manage suspected food intolerance in IBS, with a particular interest in the role of FODMAPs and the effects of a low FODMAP diet. We reviewed literature, consulting PubMed and Medline by using the search terms FODMAP(s), fructose, lactose, fructans, galactans, polyols (sorbitol, mannitol, maltitol, xylitol, erythritol, polydextrose, and isomalt), irritable bowel syndrome, and functional gastrointestinal symptoms. FODMAP-restricted diets have been used for a long time to manage patients with IBS. The innovation in the so-called FODMAP concept is that a global restriction should have a more consistent effect than a limited one in preventing abdominal distension. Even though all the potential low FODMAP diets provide good relief of symptoms in many patients, there is just a little relief in others. Several studies highlight the role of low FODMAP diets to improve symptoms in patients with IBS. The evidence on this dietary approach supports the hypothesis that a low FODMAP diet should be the first dietary approach. However, many points remain to be clarified, including the evaluation of possibly significant nutrition concerns

Multiple sclerosis-like neurological manifestations in a coeliac patient: nothing is as it seems

Cobalamin (vitamin B(12)) deficiency occurs with several disorders, involving different organs and systems, including blood, bowel, nervous system and eyes. Although the most important features are usually haematological ones, presence of neurological involvement, in the absence of blood count alterations, has just been described in the literature. Here we report the case of a 48-year-old man, suffering from coeliac disease for approximately 5 years, vegetarian, who was admitted to our department, referring dysaesthesia of the left lower limb, decreased libido and erectile dysfunction. Vitamin B(12) deficiency was proved, even in the absence of blood count alteration, and treated with a vitamin supplement, resulting in complete remission