Gluten Withdrawal Research Articles

Immune Response to Rotavirus and Gluten Sensitivity.

Rotavirus is a double-stranded RNA virus belonging to the family of Reoviridae. The virus is transmitted by the faecal-oral route and infects intestinal cells causing gastroenteritis. Rotaviruses are the main cause of severe acute diarrhoea in children less than 5 years of age worldwide. In our previous work we have shown a link between rotavirus infection and celiac disease. Nonceliac gluten sensitivity (NCGS) is emerging as new clinical entity lacking specific diagnostic biomarkers which has been reported to occur in 6–10% of the population. Clinical manifestations include gastrointestinal and/or extraintestinal symptoms which recede with gluten withdrawal. The pathogenesis of the disease is still unknown. Aim of this work is to clarify some aspects of its pathogenesis using a gene array approach. Our results suggest that NCGS may have an autoimmune origin. This is based both on gene expression data (i.e., TH17-interferon signatures) and on the presence of TH17 cells and of serological markers of autoimmunity in NCGS. Our results also indicate a possible involvement of rotavirus infection in the pathogenesis of nonceliac gluten sensitivity similarly to what we have previously shown in celiac disease.

Histologic recovery among children with celiac disease on a gluten-free diet. A long-term follow-up single-center experience.

IntroductionCeliac disease (CD) is defined by gluten-induced immune-mediated enteropathy, affecting approximately 1% of the genetically predisposed population. The immunologic response to gluten causes characteristic intestinal alterations with gradual development. Histologic recovery of intestinal architecture was reported to occur within 6–12 months after starting a gluten-free diet, simultaneously with clinical remission. The aim of this study was to assess the rate and timing of histologic recovery among children with CD on a gluten-free diet, diagnosed and followed in an academic referral pediatric center during a 10-year period.Material and methods105 biopsy-confirmed CD children underwent follow-up small intestinal biopsies within at least 1 year after dietary gluten withdrawal. Further biopsies were performed if villous alterations were persistent. The Marsh classification modified by Oberhuber was used to score the histologic injuries. ResultsIn all 19 cases with Marsh type II at diagnosis, villous alterations normalized to Marsh type 0 within the first year. From 86 children enrolled with Marsh type III lesions, histologic remission was observed in 81.4% after 1 year, 91.8% within 2–3 years and 97.6% in long-term follow up (≥ 3 years). Two (2.3%) patients with concomitant selective IgA deficiency had symptoms of malabsorption and persisting villous atrophy lasting more than 3 years despite a gluten-free diet. There was a significant statistic difference between the proportion of children with Marsh type IIIA, type IIIB and Marsh type IIIC respectively that achieved histologic recovery within 1 to 2 years after gluten withdrawal. There were more children with partial 25 (92.6%) and subtotal villous atrophy 30 (88.2%) showing histologic improvement, compared to only 15 (60%) patients with total villous atrophy that recovered within the first 2 years of diet (p = 0.01 and p = 0.02 respectively).ConclusionsHistologic recovery in CD after starting a gluten-free diet in children takes at least 1 year and might be incomplete only in a small proportion of children, mainly associated with IgA immunodeficiency. Systematic follow-up of children with CD and persistent malabsorption syndrome is needed in order to avoid secondary complications.

Adverse effects of gluten ingestion and advantages of gluten withdrawal in nonceliac autoimmune disease.

In light of the coincident surge in overall gluten intake and the incidence of autoimmune diseases, the possible biological adverse effects of gluten were explored. PubMed, MEDLINE, and the Cochrane Library databases were screened for reports published between 1964 and 2016 regarding the adverse effects of gluten as well as the effects of a gluten-free diet on autoimmune diseases. In vitro and in vivo studies describing gluten intake in animal models or cell lines and gluten-free diets in human autoimmune diseases were reviewed. Multiple detrimental aspects of gluten affect human health, including gluten-dependent digestive and extradigestive manifestations mediated by potentially immunological or toxic reactions that induce gastrointestinal inadequacy. Gluten affects the microbiome and increases intestinal permeability. It boosts oxidative stress and affects epigenetic behavior. It is also immunogenic, cytotoxic, and proinflammatory. Gluten intake increases apoptosis and decreases cell viability and differentiation. In certain nonceliac autoimmune diseases, gluten-free diets may help curtail the adverse effects of gluten. Additional in vivo studies are needed to unravel the puzzle of gluten effects in humans and to explore the potential beneficial effects of gluten-free diets in autoimmune diseases.

Are Non-Celiac Autoimmune Diseases Responsive to Gluten-Free Diet?

Genetic risk factors for autoimmune diseases are constantly discovered, however, environmental factors are laggingbehind and the precipitating events leading to development of autoimmune diseases remain enigmatic. Gluten is a well-established inducing nutrient in celiac disease and gluten withdrawal is the only current effective therapy. More and more studies have shown that non-celiac autoimmune diseases can partially respond to gluten free diet. The present editorial reviews those conditions and suggest multiple potential mechanisms that might operate in clinical amelioration of non-celiac autoimmune diseases.

Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity

Non-celiac gluten sensitivity is characterized by symptom improvement after gluten withdrawal in absence of celiac disease. The mechanisms of non-celiac gluten sensitivity are unclear, and there are no biomarkers for this disorder. Foods with gluten often contain fructans, a type of fermentable oligo-, di-, monosaccharides and polyols. We aimed to investigate the effect of gluten and fructans separately in individuals with self-reported gluten sensitivity. We performed a double-blind crossover challenge of 59 individuals on a self-instituted gluten-free diet, for whom celiac disease had been excluded. The study was performed at Oslo University Hospital in Norway from October 2014 through May 2016. Participants were randomly assigned to groups placed on diets containing gluten (5.7 g), fructans (2.1 g), or placebo, concealed in muesli bars, for 7 days. Following a minimum 7-day washout period (until the symptoms induced by the previous challenge were resolved), participants crossed over into a different group, until they completed all 3 challenges (gluten, fructan, and placebo). Symptoms were measured by Gastrointestinal Symptom Rating Scale Irritable Bowel Syndrome (GSRS-IBS) version. A linear mixed model for analysis was used. Overall GSRS-IBS scores differed significantly during gluten, fructan, and placebo challenges; mean values were 33.1 ± 13.3, 38.6±12.3, and 34.3 ± 13.9, respectively (P= .04). Mean scores for GSRS-IBS bloating were 9.3 ± 3.5, 11.6 ± 3.5, and 10.1 ± 3.7, respectively, during the gluten, fructan, and placebo challenges (P= .004). The overall GSRS-IBS score for participants consuming fructans was significantly higher than for participants consuming gluten (P= .049), as was the GSRS bloating score (P= .003). Thirteen participants had the highest overall GSRS-IBS score after consuming gluten, 24 had the highest score after consuming fructan, and 22 had the highest score after consuming placebo. There was no difference in GSRS-IBS scores between gluten and placebo groups. In a randomized, double-blind, placebo-controlled crossover study of individuals with self-reported non-celiac gluten sensitivity, we found fructans to induce symptoms, measured by the GSRS-IBS. Clinicaltrials.gov no: NCT02464150.

Gluten-free Diet - Tough Alley in Torrid Time

Dietitians play a pivotal role in the education, follow-up and navigation of the gluten-free diet for patients affected by celiac disease. Since gluten withdrawal is the cornerstone of celiac disease therapy, and since various future therapeutic strategies, are not yet on the market, the patients relay heavily on the registered dietitian nutritionists (RDNs) advice and service to cope with the gluten-free diet tough alley. Unfortunately, gluten withdrawal, nowadays, represent also a torrid time. The actual surge in incidence, wheat content, gluten intake, celiac disease-related T-cell stimulatory epitopes in wheat, usage in the processed food industries, nutritional deficiencies, changing phenotype and the fact that gluten is potentially detrimental to humankind health, make the RDNs role more complex, difficult and challenging. The present review expands on the gluten-free diet related tough alley in torrid time, which the registered dietitian nutritionists are facing when dealing with gluten-sensitive patients.

Whole lipid profile and not only HDL cholesterol is impaired in children with coexisting type 1 diabetes and untreated celiac disease.

Low HDL cholesterol (HDL-C) levels have been described in patients with coexisting type 1 diabetes mellitus (T1DM) and celiac disease (CD). Data on other possible lipid abnormalities that could further increase cardiovascular risk in these patients are scarce and incomplete. Aim of this retrospective multicenter study was to evaluate whole lipid profiles, besides HDL-C, in children with T1DM associated with biopsy-proven CD, and to investigate the influence of age and degree of adherence to gluten-free diet (GFD) on lipid changes. A total of 261 children with both T1DM and CD were enrolled. Serum lipid profiles at CD diagnosis were compared with those after 1year of GFD and with those of 224 matched children with T1DM alone. The adherence to GFD was judged by means of CD-related antibodies. At CD diagnosis, children with T1DM+CD showed higher LDL cholesterol (LDL-C) compared to children with T1DM alone. Gluten withdrawal failed to normalize LDL-C levels, not even in completely adherent individuals. HbA1c values were not influenced by GFD. The youngest children were characterized at diagnosis by lower levels of total cholesterol and on treatment by a greater decrease in triglycerides levels. An unfavorable lipid profile, characterized not only by low HDL-C levels but also by high LDL-C values, may increase the risk of cardiovascular disease in children with T1DM and untreated CD. Therefore, a strict gluten-free diet is mandatory in these children, especially the youngest.

Challenges in gluten-free diet in coeliac disease: Prague consensus.

New treatments in coeliac disease are being vigorously pursued to either replace or facilitate the difficult-tofollow gluten-free diet. The present review intends to summarise the challenges in gluten-free diet adherence during the transitional period, as reflected in the last Prague consensus, published in 2016. The honourable panel members recommended that dietary adherence and the consequences of nonadherence represent key components for discussion in the transitional period setting. There are numerous difficulties in adhering to gluten withdrawal, but the transition period from adolescence to young adulthood is considered a fragile and high-risk period for intentional and unintentional gluten intake.

Hemophagocytic lymphohistiocytosis responding to withdrawal of gluten: a case report.

BackgroundThis is the first documented case of a patient with hemophagocytic lymphohistiocytosis in association with coeliac disease. There was complete clinical and biochemical remission of hemophagocytic lymphohistiocytosis following the introduction of a gluten-free diet.Case presentationA 7-year-old white girl presented with fevers and maculopapular rash with a recent history of tonsillitis. Blood tests revealed thrombocytopenia (64×109/L), anemia (80 g/L), hypofibrinogenemia (1 g/L), and hyperferritinemia (71,378 μg/L). A bone marrow revealed evidence of hemophagocytosis, but the results of tests for the genetic or familial-associated hemophagocytic lymphohistiocytosis syndromes were negative. The results of screening tests for known secondary causes were negative. She was diagnosed as having hemophagocytic lymphohistiocytosis and following treatment with the hemophagocytic lymphohistiocytosis-2004 protocol these symptoms, in addition to the biochemical and hematological markers, completely resolved.She presented again 10 months later with fever, rash, and biochemical abnormalities suggestive of hemophagocytic lymphohistiocytosis. Her tissue transglutaminase was markedly raised and the results of blood tests revealed a genetic susceptibly to coeliac disease in the form of HLA-DQ2 positivity. She commenced a gluten-free diet and there was complete symptomatic and biochemical response without any further chemotherapy. She had further episodic rashes, each associated with the accidental intake of gluten.ConclusionsThis is to the best of our knowledge the first documented case of hemophagocytic lymphohistiocytosis in association with coeliac disease. No other secondary cause found; she initially responded to chemoimmunotherapy specific for hemophagocytic lymphohistiocytosis but relapsed within a few months of cessation of treatment and then achieved complete remission on gluten withdrawal alone.

Microbial Proteases in Baked Goods: Modification of Gluten and Effects on Immunogenicity and Product Quality.

Gluten-related diseases are a range of inflammatory disorders of the small intestine, characterized by an adverse response to gluten ingestion; therefore, the treatment is a gluten withdrawal. In spite of the increased market of gluten-free products, widely available breads with high acceptability are still missing due to the technological challenge of substituting the special gluten properties. Instead of using alternative ingredients for baking, some attempts have been done to decrease gluten immunogenicity by its enzymatic degradation with microbial proteases. Although the gluten immunogenicity reduction has been reached to an acceptable level, some quality parameters of the products are affected. This review focus on the use of microbial peptidases to prepare less immunogenic baked goods and their effect on product quality.

Improving outcomes of refractory celiac disease - current and emerging treatment strategies.

Intestinal inflammation and symptoms of celiac disease (CD) usually respond well to gluten withdrawal, but rare cases are refractory to diet. Two types of refractory CD are discriminated on the basis of the presence or absence of an atypical population of mucosal lymphocytes that may progress to enteropathy-associated T-cell lymphoma. Challenges remain in the secure diagnosis of both types of refractory disease, and evidence on which to base treatment recommendations is flawed by the small numbers of reported patients and the use of different diagnostic strategies. Recent advances in our understanding of the mechanisms of the condition in conjunction with the development of immunomodulatory agents for managing other inflammatory diseases are helping to shape future approaches to targeted therapy. Progression will depend on collaboration and recruitment to trials. In the meantime, there is evidence to suggest that earlier diagnosis and better follow-up and management of CD may prevent the development of refractoriness.

Delayed gastric emptying does not normalize after gluten withdrawal in adult celiac disease

ABSTRACTObjective Delayed gastric emptying has been frequently detected in patients with untreated celiac disease. According to several studies, gluten withdrawal showed to be effective in normalizing the gastric emptying rate. The aim of this study was to evaluate the gastric emptying rate of solids in patients with celiac disease before and after a gluten-free diet. Methods Twelve adult patients with celiac disease (age range 20–57 years) and 30 healthy controls (age range 30–54 years) underwent a 13C-octanoic acid breath test to measure gastric emptying. Half emptying time (t1/2) and lag phase (tlag) were calculated. After at least 12 months of a gluten-free diet, celiac patients underwent a new 13C-octanoic acid breath test. A symptom score was utilized to detect dyspeptic and malabsorption symptoms in all the patients. Results The gastric motility parameters, t1/2 and tlag, were significantly longer in patients than in controls. On a gluten-free diet, surprisingly, the gastric emptying did not normalize despite an improvement of symptom score. No significant correlation between abnormal gastric emptying and specific symptom patterns, anthropometric parameters or severity of histological damage was found. Conclusions This finding supports the hypothesis that gluten-driven mucosal inflammation might determine motor abnormalities by affecting smooth muscle contractility or impairing gut hormone function. The persistence of these abnormalities on a gluten free diet suggests the presence of a persistent low-grade mucosal inflammation with a permanent perturbation of the neuro-immunomodulatory regulation.

Severe Iron-deficiency Anemia and Celiac Disease

We report a case of a 37-year-old woman with atypical presentation of celiac disease in relation to severe iron-deficiency and hyperthyroidism. During the investigation for iron-deficiency anemia, after exclusion of hematologic disorders, she was diagnosed with celiac disease by small-bowel biopsy. After starting the gluten free diet, the serum hemoglobin values were corrected and the symptoms of hyperthyroidism improved. Our presentation demonstrates that for patients with severe iron-deficiency anemia, the examination for the celiac disease should be considered. The quality of life and morbidity of patients with hyperthyroidism, iron-deficiency anemia and celiac disease may be improved by gluten withdrawal.

Screening for Coeliac Disease: Are We Good at It?

Department of Paediatrics, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland Coeliac disease (CD) is an immune reaction to gluten in genetically predisposed subjects. CD is likely to affect approximately 1% of the population of England [1]. The age of presentation is influenced by the age of introduction of gluten into the diet. CD may present as a large variety of non-specific signs and symptoms. Children with CD may experience unexplained poor growth following the introduction of gluten, delay puberty, abnormal stools and constipation. General irritability, chronic abdominal pain, abnormal liver biochemistry, abdominal distension and buttock wasting have been reported. CD should be considered in children presented with iron deficiency anaemia, growth failure with or without gastrointestinal symptoms. Patients with CD may experience low bone mineral density [2], but similar health-related quality of life as their peers without CD [3]. However individuals with CD may exhibit no symptoms. Certain individuals are at an increased risk; such as patients with type 1 diabetes mellitus, Down’s syndrome and Turner’s syndrome, for example, and presymptomatic screening is advised [4]. Diagnosis can be confirmed by flat mucosa on jejunal biopsy followed by the resolution of symptoms and catch up growth upon gluten withdrawal. Diagnostic serological tests have been developed. These’s include IgA anti-tissue transglutaminase (IgA-tTG) and antiendomysium antibody (EMA) values. It is important to measure serum IgA level and IgG-tTG values should be considered in those with low IgA levels. In previous study, biopsyproven CD and positive EMA were reported in 60% of those with elevated IgA-tTG levels above the reference range, whereas biopsy-proven CD was reported in all patients with positive EMA [5]. European Society for Paediatric Gastroenterology, Hepatology and Nutrition working group suggested that typing for HLA-DQ2 and HLA-DQ8 can be helpful where there is uncertain diagnosis of CD; such as cases with negative CD antibodies and mild changes on biopsy or with strong clinical suspicion, highly specific CD antibodies and biopsies are not going to be performed, for example [4]. Monitoring for CD is required in children with unexplained poor growth, delayed puberty or unexplained gastrointestinal symptoms and screening in asymptomatic individuals who are at an increased risk is advised.

Carotid intima-media thickness and arterial stiffness as early markers of atherosclerosis in pediatric celiac disease.

The association between pediatric celiac disease (CD) and atherosclerosis is unknown. Our aim was to investigate whether pediatric CD patients have an increased risk of atherosclerosis. We evaluated the premature atherosclerosis by pulse wave velocity (PWV) and carotid intima-media thickness (cIMT). A total of 37 CD patients (20 girls, mean age 13±3.3 years) and 36 healthy age and sex matched controls were enrolled. Mean duration of CD was 47.1±32.3 months and 40.5% of patients had positive tissue transglutaminase antibody (tTg) IgA. Total cholesterol level was lower in CD (p=0.026) and cIMT was lower in tTg IgA antibody negative CD (p=0.030). cIMT was significantly correlated with tTg IgA antibody positivity (r=0.336; p=0.042). Adherence to strict gluten-free diet is associated with decreased cIMT, suggesting that gluten withdrawal seems to have a beneficial effect on premature atherosclerosis.

Features and Progression of Potential Celiac Disease in Adults.

Individuals with potential celiac disease have serologic and genetic markers of the disease with little or no damage to the small intestinal mucosa. We performed a prospective study to learn more about disease progression in these people. We collected data from 77 adults (59 female; median age, 33 years) diagnosed with potential celiac disease (on the basis of serology and HLA type) at Bologna University in Italy from 2004 through 2013. The subjects had normal or slight inflammation of the small intestinal mucosa. Clinical, laboratory, and histologic parameters were evaluated at diagnosis and during a 3-year follow-up period. Sixty-one patients (46 female; median age, 36 years) showed intestinal and extraintestinal symptoms, whereas the remaining 16 (13 female; median age, 21 years) were completely asymptomatic at diagnosis. All subjects tested positive for immunoglobulin A endomysial antibody and tissue transglutaminase antibody, except for 1 patient with immunoglobulin A deficiency; 95% of patients were carriers of HLA-DQ2. Duodenal biopsies from 26% patients had a Marsh score of 0, and 74% had a Marsh score of 1. A higher proportion of symptomatic patients had autoimmune disorders (36%) and antinuclear antibodies (41%) than asymptomatic patients (5% and 12.5%, respectively), and symptomatic patients were of older age at diagnosis (P < .05). Gluten withdrawal led to significant clinical improvement in all 61 symptomatic patients. The 16 asymptomatic patients continued on gluten-containing diets, and only 1 developed mucosal flattening; levels of anti-endomysial and tissue transglutaminase antibodies fluctuated in 5 of these patients or became undetectable. In a 3-year study of adults with potential celiac disease, we found most to have symptoms, but these improved on gluten withdrawal. Conversely, we do not recommend a gluten-free diet for asymptomatic adults with potential celiac disease because they do not tend to develop villous atrophy.

Histological evaluation of duodenal biopsies from coeliac patients: the need for different grading criteria during follow-up.

BackgroundCoeliac disease is characterised by villous atrophy, which usually normalises after gluten withdrawal. Sometimes the revaluation of duodenal histology is required during follow-up, even if the methodology for comparing duodenal histology before and after introducing a gluten-free diet is not yet established. Our aim was to evaluate a novel criterion to compare duodenal histology in coeliac disease before and after gluten withdrawal.MethodsDuodenal biopsies from coeliac patients were retrospectively reviewed to compare duodenal histology at diagnosis and after at least one year on a gluten-free diet. Two different methods were used: the first was represented by the classical Marsh-Oberhuber score, the second compared the areas covered by each Marsh-Oberhuber grade and expressed as percentages, the final grade being calculated from the analysis of ten power fields per duodenal biopsy.ResultsSixty-nine patients (17 males 52 females, age at diagnosis 36 ± 15 years) who underwent duodenal biopsies, were considered. According to the classical Marsh-Oberhuber scale, 32 patients did not present atrophy during follow-up while 37 showed duodenal atrophy, among whom 26 improved the grade of severity and 11 retained the same one. Of these latter, according to the second method, eight patients were considered improved, two showed a worsened duodenal damage and only one remained unchanged; the evaluation changed in 91 % of cases.ConclusionsThe proposed semi-quantitative approach (i.e. the second method) for the evaluation of histology at follow-up provides additional information about the progression/regression of the mucosal damage.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-015-0361-8) contains supplementary material, which is available to authorized users.

Celiac Crisis: A Rare Manifestation of a Common Disease

Introduction: Celiac crisis is a rare and life threatening manifestation of celiac disease. Case presentation: We present a 46 year old male with a history of DM1 complicated by ESRD on HD and a recent diagnosis of Bell's Palsy who was admitted from a dialysis center with hypotension and voluminous diarrhea. Reported up to 20 watery, nonbloody bowel movements per day x 7 days. The diarrhea was associated with LLQ crampy pain. Denied fevers. +Nocturnal diarrhea. The diarrhea did not improve with fasting. Denied recent weight loss.Figure 1Figure 2Figure 3Vital Signs and PE: Afebrile BP 55/42 Pulse 102. Dry mucous membranes. Mild LLQ tenderness with hyperactive bowel sounds. A rectal tube was in place with voluminous light brown watery stool identified. Inital laboratory results and imaging. 6.8/11\173. 130 | 98 | 98. 4.6 | 19 | 13.4. pH 7.27 Alb 2.9 Ca 7.2 C. Diff PCR negative CT abdomen and pelvis with IV contrast revealed mild thickening of proximal small bowel loops, suspicious for enteritis. Further pertinent labs: Stool 0 + P and culture negative. Lactoferrin: positive. ESR and CRP elevated. TTG IgA 80 (0-19). Gliadin IgA 39 (0-19). Stool Osmolar gap 36 Gastrin and VIP normal 5HIAA excretion normal. Over a 24 hour period, the patient required 13 L's of IVF's to keep up with GI losses and maintain blood pressure. An esophagogastroduodenoscopy revealed scalloping in the duodenal bulb and 2nd part of the duodenum. Biopsies were obtained and revealed villous atrophy, increased intraepithelial lymphocytes, and crypt hyperplasia (Marsh 3C). The diagnosis of celiac crisis was made based on the endoscopic and serologic results in conjuction with the dramatic presentation. After 3 days of gluten withdrawal our patients bowel movement frequency and caliber improved dramatically. Discussion: In this rare manifestation of celiac disease marked metabolic derangements are encountered. It is unclear what triggers this more aggressive disease course, however it has been suggested to be a combination of severe mucosal inflammation and immune activation.1 In our case, we propose that his recent diagnosis of Bell's Palsy precipitated an immune activation leading to the crisis. Celiac disease should be considered in adults presenting with acute voluminous diarrhea and profound electrolyte abnormalities.

Non-celiac gluten sensitivity: Another condition that responds to 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.

Celiac Disease, Refractory Celiac Disease, and Tropical Sprue

Celiac disease, often also termed celiac sprue, is an immune-mediated disorder triggered by ingestion of wheat, barley, rye, and triticale gluten proteins in genetically predisposed individuals. The offending glutens induce a characteristic but variable and nonspecific lesion of the small intestinal mucosa that improves following gluten withdrawal. Patients with refractory celiac disease (RCD) have persistent or recurrent symptomatic malabsorption together with biopsy-documented enteropathy that has not responded to 6 to 12 months of strict gluten withdrawal. Tropical sprue is an illness that occurs in individuals living in tropical countries; clinical features include anorexia, diarrhea, and intestinal malabsorption, leading to weight loss accompanied by a characteristic although nonspecific lesion of the mucosa of the small intestine. This review addresses the epidemiology, etiology/genetics, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, complications, and prognosis of these related diseases. Figures show the celiac disease iceberg, duodenal mucosal surface seen at endoscopy, duodenal mucosal biopsies from a patient with celiac disease, higher magnification micrograph of the duodenal mucosal surface from a patient with untreated celiac disease, duodenal biopsies from a patient with refractory celiac disease, and duodenal biopsy obtained from an Indian expatriate with diarrhea, weight loss, and folate deficiency. Tables list selected extraintestinal manifestations of celiac disease, prevalence of celiac disease in selected conditions, disorders with duodenal lesions that may mimic those of celiac diseases, initial treatment for celiac disease, organizations that provide helpful information for gluten-intolerant patients, considerations in a patient not responding to a gluten-free diet, and features that help distinguish tropical sprue from celiac disease. This review contains 6 highly rendered figures, 7 tables, and 96 references.