Alfredo J. Lucendo

Nutritional and Dietary Aspects of Celiac Disease

Celiac disease (CD) is a primarily digestive systemic disease triggered and maintained by the ingestion of gluten in the diet. Its has a wide clinical spectrum of manifestations, particularly varied in adult patients, in whom, because of their frequent negative serology and mild, nonspecific symptoms, there is a considerable delay in diagnosis. The intestinal lesion caused by CD leads to various deficiencies of nutrients, vitamins, and dietary minerals, with ferropenia, vitamin B12, folic acid, and fat-soluble vitamin deficiencies being especially frequent. The deficiencies, together with dairy intolerance, cause low bone density and an increased risk of fractures. Treatment using a gluten-free diet (GFD) does involve certain complications, since gluten is found in up to 70% of manufactured food products and manufacturing regulations are not standard in all countries. In addition, certain nutrient deficiencies require specific management. This article reviews the nutritional aspects of CD and provides practical guidelines to correct these deficiencies and to ensure optimum GFD compliance.

Adult versus pediatric eosinophilic esophagitis: important differences and similarities for the clinician to understand

Eosinophilic esophagitis (EoE) is recognized as a common, allergy-associated cause of chronic esophageal symptoms affecting both children and adults. Research has begun to shed light on its epidemiology with consistent results from various geographical areas. Differences in clinical presentation, endoscopic aspects and response to treatment have all been reported for patients of different ages, and the question as to whether adult and pediatric EoE are manifestations of a single entity or in fact two distinct disorders has been posed. The most relevant differences between pediatric and adult EoE come from evolutionary changes in the consequences of the disease, including fibrous remodeling, and the ability to express symptoms. However, most studies support a common pathogenesis and similar histopathological features for adult and pediatric patients, being the same diagnostic criteria applied to them. This article comprehensively reviews the most recently published information and addresses important questions about the natural history of EoE.

The role of mast cells in eosinophilic esophagitis

Eosinophilic esophagitis (EE) is a chronic inflammatory disease of the esophagus which is characterized by the presence of dense infiltrate of eosinophilic leukocytes restricted to this organ mucosa. Accumulating published evidence suggests a strong role of mast cells in the inflammatory infiltrate in the physiopathology of EE. We have reviewed published articles with relevant information about the presence and possible role of mast cells in EE. Although mast cells have been studied indirectly in EE, reported data allow us to confirm that the number of mast cells infiltrating the esophageal epithelium in adult and child patients with EE is higher with respect to the normal state and in gastroesophageal reflux disease. Mast cells linked to IgE, which are not found in other conditions, have been identified in EE. Despite that fact, an anaphylactic reaction history after exposure to allergens is not common in these patients. Therefore, the mast cells’ function in EE could be dependent on T lymphocytes, as suggested by a mast cell gene expression analysis. Bi‐directional crosstalk is established between mast cells and eosinophils, hence establishing interesting hypotheses regarding their relationship to EE physiopathology. Mast cells’ function as an immune response leader seems to substitute for their effector functions in EE, while at the same time opening new research pathways for consideration of these cells as a therapeutic target in EE. However, the inefficiency of therapies that inhibit mast cell functions while they are effective in other respiratory tract diseases results in the need for specific studies to identify the real function of such complex cells in the physiopathology of EE. There is indirect proof of the role of mast cells in EE, while many doubts exist about their activation mechanism, which does not seem to be IgE‐mediated. Specific approach studies are needed to clarify the function of these cells in the physiopathology of EE, which could be a possible therapeutic target.

Eosinophilic gastroenteritis: an update

Eosinophilic gastroenteritis (EGE) is characterized by dense eosinophilic inflammation of one or several digestive tract sections. The symptoms include abdominal pain, weight loss, vomiting and diarrhea. Biopsy samples taken during endoscopic examination allows the diagnosis of the disease. An infiltration of >30 eosinophils per high-power field in at least five high-power fields, exhibiting signs of eosinophilic degranulation and extending to the muscularis mucosa or submucosa are all histological indications of EGE. EGE is traditionally classified into three forms depending on the depth of inflammation in the wall (mucosal, muscular or serosal). This, together with the digestive tract segments involved, determines the clinical presentation. The natural history of EGE includes three different evolutionary patterns, since patients may suffer a single outbreak, a recurrent course or even chronic disease. Corticosteroids are the most frequently used therapy for EGE; dietary treatments should be also considered. Surgery has been limited to solving obstruction and small bowel perforation.

An update on the immunopathogenesis of eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic clinicopathological entity characterized by large numbers of intraepithelial eosinophils infiltrating the esophageal mucosa, which is not caused by gastroesophageal reflux. This disease has become widely recognized over the past few years and new methods have been developed to reveal its underlying pathophysiological mechanisms. Owing to the high prevalence of food and/or airborne allergen sensitization in EoE patients, the allergic nature of the disease had to be defined, which has certain factors in common with other IgE-dependent entities, such as bronchial asthma or allergic rhinitis. Of these, some cytokines and chemokines previously studied in asthma have also been implicated in molecular mechanisms causing eosinophil-rich esophageal inflammation. However, the role played by IgE in relation to the esophageal eosinophilic infiltrate must be clarified, together with the possible function of mast cells in the inflammatory infiltrate and its activation stimuli. A putative role has also been recently suggested for gastroesophageal reflux in the origin of EoE that should be profoundly analyzed, together with the role of specific genes implicated in other digestive inflammatory disorders. This article reviews recent advances in the immunopathogenesis of EoE, which should also consider other pathways to activate the esophageal mucosal immune system.

Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 study

Background: Numerous dietary restrictions and endoscopies limit the implementation of empiric elimination diets in patients with eosinophilic esophagitis (EoE). Milk and wheat/gluten are the most common food triggers. Objective: We sought to assess the effectiveness of a step‐up dietary strategy for EoE. Methods: We performed a prospective study conducted in 14 centers. Patients underwent a 6‐week 2‐food‐group elimination diet (TFGED; milk and gluten‐containing cereals). Remission was defined by symptom improvement and less than 15 eosinophils/high‐power field. Nonresponders were gradually offered a 4‐food‐group elimination diet (FFGED; TFGED plus egg and legumes) and a 6‐food‐group elimination diet (SFGED; FFGED plus nuts and fish/seafood). In responders eliminated food groups were reintroduced individually, followed by endoscopy. Results: One hundred thirty patients (25 pediatric patients) were enrolled, with 97 completing all phases of the study. A TFGED achieved EoE remission in 56 (43%) patients, with no differences between ages. Food triggers in TFGED responders were milk (52%), gluten‐containing grains (16%), and both (28%). EoE induced only by milk was present in 18% and 33% of adults and children, respectively. Remission rates with FFGEDs and SFGEDs were 60% and 79%, with increasing food triggers, especially after an SFGED. Overall, 55 (91.6%) of 60 of the TFGED/FFGED responders had 1 or 2 food triggers. Compared with the initial SFGED, a step‐up strategy reduced endoscopic procedures and diagnostic process time by 20%. Conclusions: A TFGED diet achieves EoE remission in 43% of children and adults. A step‐up approach results in early identification of a majority of responders to an empiric diet with few food triggers, avoiding unnecessary dietary restrictions, saving endoscopies, and shortening the diagnostic process.

Small bowel video capsule endoscopy in Crohn’s disease: What have we learned in the last ten years?

Since its introduction in 2001, capsule endoscopy (CE) has become the most important advance in the study of small bowel disease, including Crohns disease (CD). This technique has been demonstrated to be superior to all other current forms of radiological investigation in detecting mucosal abnormalities of small bowel nonstricturing CD. CE has proven to be extremely useful in diagnosing CD in patients with inconclusive findings from ileocolonoscopy and x-ray-based studies. Almost half of all patients with CD involving the ileum also present lesions in proximal intestinal segments, with the small bowel being exclusively involved in up to 30% of all CD cases. Despite the widespread use of CE, several questions concerning the utility of this technique remain unanswered. The lack of commonly agreed diagnostic criteria for defining CD lesions with the aid of CE may have had an influence on the variation in diagnostic results for CE reported in the literature. The utility of CE in monitoring CD and in guiding therapy has also been proposed. Furthermore, CE could be a useful second-line technique for patients with an established diagnosis of CD and unexplained symptoms. Finally, as no threshold for CD diagnosis has been agreed upon, a severity scale of mucosal disease activity has not been universally followed. None of the available activity indexes based on CE findings has been independently validated. This article discusses several cutting-edge aspects of the usefulness of CE in CD 10 years after its introduction as a sensible method to study the small intestine.

Resolution of metabolic syndrome after following a gluten free diet in an adult woman diagnosed with celiac disease

Adult celiac disease (CD) presents with very diverse symptoms that are clearly different from those typically seen in pediatric patients, including ferropenic anemia, dyspepsia, endocrine alterations and elevated transaminase concentration. We present the case of a 51-year-old overweight woman with altered basal blood glucose, hypercholesterolemia, hypertriglyceridemia and persisting elevated transaminase levels, who showed all the symptoms for a diagnosis of metabolic syndrome. Because she presented iron deficiency anemia, she was referred to the gastroenterology department and subsequently diagnosed with celiac disease after duodenal biopsies and detection of a compatible HLA haplotype. Gluten-free diet (GFD) was prescribed and after 6 mo the patient showed resolution of laboratory abnormalities (including recovering anemia and iron reserves, normalization of altered lipid and liver function parameters and decrease of glucose blood levels). No changes in weight or waist circumference were observed and no significant changes in diet were documented apart from the GFD. The present case study is the first reported description of an association between CD and metabolic syndrome, and invites investigation of the metabolic changes induced by gluten in celiac patients.

Eosinophilic esophagitis: latest insights from diagnosis to therapy

Eosinophilic esophagitis (EoE) represents a chronic, local immune‐mediated esophageal disease, characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil‐predominant inflammation. Other systemic and local causes of esophageal eosinophilia should be excluded. Clinical manifestations or pathologic data should not be interpreted in isolation. EoE was first described as a distinct disease entity in 1993. Most patients are diagnosed with underlying food allergies. The first diagnostic and therapeutic guidelines were published in 2007 with a first update in 2011. In 2017, new international guidelines were published based on the GRADE methodology. These guidelines provide, among many other topics, insights on the role of proton pump inhibitor‐responsive esophageal eosinophilia. Over the last two decades, considerable progress was made by stakeholders regarding the understanding of EoEs pathogenesis, genetic background, natural history, allergy workup, standardization of assessment of disease activity, evaluation of minimally invasive diagnostic tools, and new therapeutic approaches. This brief review provides further insights into latest diagnostic and therapeutic advances.