Enteric-Release Budesonide May Be Useful in the Management of Non-Responsive Celiac Disease.

BACKGROUND: Non-responsive celiac disease (NRCD) has many aetiologies, including gluten exposure. Budesonide may be used for refractory celiac disease (RCD) and celiac crisis. AIMS: We reviewed the effectiveness of budesonide to induce clinical and histologic response in NRCD with villous atrophy (VA). METHODS: Case series of adult cases with NRCD and VA prescribed budesonide at two celiac centers. Clinical variables and mucosal recovery (i.e., normal villous architecture within 1 year of treatment) were evaluated. RESULTS: Forty-two cases [77% female, median age 45.0 (IQR 28.3-60.0) years] were included. Most common symptoms were diarrhea (64%) and abdominal pain (62%). Budesonide was initiated at 9 mg (83%) for a median duration of 16.0 weeks (IQR 6.8-25.0 weeks). In total, 57% exhibited a clinical response, positively associated with diarrhea (adjusted OR 6.08 95% CI 1.04-35.47) and negatively with fatigue (adjusted OR 0.18 95% CI 0.03-0.98). Clinical response was higher among those with dietitian counseling prior to budesonide (n = 29, 70 vs. 23%, p < 0.01). Mucosal recovery was observed in 11/24 with follow-up duodenal biopsies. There was no association between clinical response and mucosal recovery, and 79% of clinical responders had a symptomatic relapse. RCD (48%) and chronic gluten exposure (24%) were the main suspected aetiologies of NRCD. Most individuals without a clinical response subsequently received an IBS-related diagnosis. CONCLUSIONS: Budesonide may be effective to induce clinical response in NRCD presenting with diarrhea and VA, but clinical recurrence and lack of mucosal recovery are frequent after tapering. Other diagnoses, including coexisting IBS, may be considered in non-responders to budesonide therapy.

Gluten and FODMAPS-Sense of a Restriction/When Is Restriction Necessary?

Gluten-free diet (GFD) is enjoying increasingly popularity, although gluten-free products are considerably more expensive. GFD is absolutely necessary for patients with celiac disease, as in this case even minor amounts of gluten can lead to the destruction of the intestinal mucosa. In addition, GFD is currently the best therapy to improve clinical symptoms of patients with non-celiac gluten sensitivity (NCGS), although the diet may not be as strict as that for patients with celiac disease. Beside gluten, other wheat components such as oligosaccharides and amylase trypsin inhibitors are discussed as triggers of NCGS in this review. An overlap between gastrointestinal symptoms in NCGS and irritable bowel syndrome (IBS) is described. Patients with NCGS attribute their symptoms to the consumption of gluten, while patients with IBS rarely describe gluten as a trigger. Recently, several studies have demonstrated that the introduction of a low FODMAP (fermentable oligo-, di-, monosaccharides, and polyols) diet reduced gastrointestinal symptoms in patients with IBS and this diet is suggested as the first choice of therapy in IBS. However, a low FODMAP diet also eliminates prebiotica and may negatively influence the gut microbiota. For this reason, the diet should be liberalized after symptom improvement. There is no evidence that a GFD is healthier than the standard diet. In contrast, GFD often is accompanied by nutritional deficiencies, mainly minerals and vitamins. Therefore, GFD and low FODMAP diets are not recommended for healthy subjects. Since wheat contains fructans belonging to FODMAPs), a GFD is not only gluten-free but also has less FODMAPs. Thus, symptom improvement cannot be correctly correlated with the reduction of either one or the other.

Metabolic interventions in Autism Spectrum Disorder.

Metabolic interventions including special diets and supplements are commonly used in Autism Spectrum Disorder (ASD). Yet little is known about how these interventions, typically initiated by caregivers, may affect metabolic function or the core symptoms of ASD. This review examines possible direct and indirect roles for metabolism in the core symptoms of ASD as well as evidence for metabolic dysfunction and nutritional deficiencies. We also discuss some of the most popular diets and supplements used in our patient population and suggest strategies for discussing the utility of these interventions with patients, families, and caregivers.

Experiences of coeliac disease in a changing gluten-free landscape.

BACKGROUND: Coeliac disease is an autoimmune disorder triggered by the ingestion of gluten. In recent years, there has been considerable increase in the availability of gluten-free products in North America. The present study investigated how the recent proliferation of the gluten-free industry has affected individuals living with coeliac disease, with a primary focus on their social lives and relationships. METHODS: Interpretive phenomenology was utilised for study design and analysis. Semi-structured interviews were conducted with 17 adults diagnosed with coeliac disease in Calgary, Alberta. Interviews were audio recorded and then transcribed for analysis. RESULTS: People living with coeliac disease experience the growth of the gluten-free industry as a 'double-edged sword'. Although they are grateful for more palatable gluten-free options, they are increasingly faced with misunderstandings about the severity of coeliac disease as a result of many noncoeliac disease individuals subscribing to the gluten-free diet. This 'double-edged sword' made certain types of social situations more easily manageable (e.g. more gluten-free options available at restaurants), whereas others produced distress (e.g. increased risk of inadvertently consuming gluten). Participants also felt they may be perceived or even perceived themselves differently (e.g. felt high maintenance). To help mitigate these social ramifications of following the gluten-free diet, participants utilised various strategies. CONCLUSIONS: The sole medical recommendation of a gluten-free diet fails to acknowledge the ongoing difficulties those with coeliac disease can endure in the current gluten-free landscape. Recommendations beyond the gluten-free diet are advisable to alleviate many of the indirect burdens revealed in the present study.

Anxiety after coeliac disease diagnosis predicts mucosal healing: a population-based study.

BACKGROUND: Coeliac disease has been linked to anxiety and depression. However, their association with mucosal healing is unknown. AIM: To examine the relationship between anxiety, depression and mucosal healing in coeliac disease. METHODS: Between 1969 and 2008, we collected data on all small intestinal biopsies with villous atrophy from Sweden's 28 pathology departments. We restricted our cohort to individuals with data on follow-up biopsy (either persistent villous atrophy [n = 3317] or mucosal healing [n = 4331]). Through Cox regression, we estimated hazard ratios (HRs) for anxiety or depression. RESULTS: During follow-up, 123 (2.8/1000 person-years) individuals with mucosal healing had developed anxiety, compared to 94 (2.1/1000 person-years) with persistent villous atrophy. Mucosal healing was hence associated with a higher risk of future anxiety (HR = 1.49; 95% CI = 1.12-1.96). Similarly, 167 (3.8/1000 person-years) individuals with mucosal healing developed depression, compared to 148 (3.3/1000 person-years) with persistent villous atrophy, corresponding to a HR of 1.25 (95% CI = 0.99-1.59). Mucosal healing was more common in individuals with prior diagnoses of anxiety or depression before follow-up biopsy. Anxiety diagnosed between diagnostic and follow-up biopsy for coeliac disease was associated with an almost nine-fold increased chance of mucosal healing (odds ratio = 8.94; 95%CI = 2.03-39.27). CONCLUSION: Anxiety and depression are more common in coeliac disease patients with mucosal healing, both before and after follow-up biopsy, an association potentially mediated through more vigilant compliance with a gluten-free diet. This finding raises concern that achieving the goal of mucosal healing may come at a cost of an increased risk of mood disorders.

Past, present and future: The strength of plant-based dairy substitutes based on gluten-free raw materials.

Plant-based foods are gaining popularity and the market is developing fast. This trend is based on several factors, like the change of lifestyle, interest in alternative diets, and the increasing awareness about sustainable production of food and especially proteins. Plant-based dairy substitutes can serve as an option to traditional food products, meeting many of these interests. However, the market is in its infancy and needs to progress. Trends show, that the market will change from being focused on mainly soya, almond and rice-based products, due to their unsustainable farming, and nutritional concerns, like genetic modification and low protein content. The market is likely to shift towards alternative plants to meet consumers' needs and desire for healthy, flavourful and intriguing products. In this regard, the aspect of allergy-free, like gluten-free products gain in importance. Research studies are approaching the nutritional quality of plant-based dairy substitutes, such as improving the protein quality and glycaemic properties. Furthermore, the application of these products or plant proteins as functional ingredients or substitutes for cow's milk in dairy products like cheese and yoghurt are disseminated. However, there is still a need for much more diversified studies in order to overcome stability, textural, nutritional and sensory problems.

Trends, geographical variation and factors associated with prescribing of gluten-free foods in English primary care: a cross-sectional study.

OBJECTIVES: There is substantial disagreement about whether gluten-free foods should be prescribed on the National Health Service. We aim to describe time trends, variation and factors associated with prescribing gluten-free foods in England. SETTING: English primary care. PARTICIPANTS: English general practices. PRIMARY AND SECONDARY OUTCOME MEASURES: We described long-term national trends in gluten-free prescribing, and practice and Clinical Commissioning Group (CCG) level monthly variation in the rate of gluten-free prescribing (per 1000 patients) over time. We used a mixed-effect Poisson regression model to determine factors associated with gluten-free prescribing rate. RESULTS: There were 1.3 million gluten-free prescriptions between July 2016 and June 2017, down from 1.8 million in 2012/2013, with a corresponding cost reduction from £25.4 million to £18.7 million. There was substantial variation in prescribing rates among practices (range 0 to 148 prescriptions per 1000 patients, IQR 7.3-31.8), driven in part by substantial variation at the CCG level, likely due to differences in prescribing policy. Practices in the most deprived quintile of deprivation score had a lower prescribing rate than those in the highest quintile (incidence rate ratio 0.89, 95% CI 0.87 to 0.91). This is potentially a reflection of the lower rate of diagnosed coeliac disease in more deprived populations. CONCLUSION: Gluten-free prescribing is in a state of flux, with substantial clinically unwarranted variation between practices and CCGs.

Latiglutenase Improves Symptoms in Seropositive Celiac Disease Patients While on a Gluten-Free Diet.

BACKGROUND AND AIMS: Celiac disease (CD) is a widespread condition triggered by dietary gluten and treated with a lifelong gluten-free diet (GFD); however, inadvertent exposure to gluten can result in episodic symptoms. A previous trial of latiglutenase (clinicaltrials.gov; NCT01917630), an orally administered mixture of two recombinant gluten-specific proteases, was undertaken in symptomatic subjects with persistent injury. The primary endpoint for histologic improvement was not met, presumably due to a trial effect. In this post hoc analysis, we investigated the efficacy of latiglutenase for reducing symptoms in subgroups of the study participants based on their seropositivity. METHODS: The study involved symptomatic CD patients following a GFD for at least one year prior to randomization. Patients were treated for 12 weeks with latiglutenase or placebo. Of 398 completed patients, 173 (43%) were seropositive at baseline. Symptoms were recorded daily, and weekly symptom scores were compiled. p values were calculated by analysis of covariance. RESULTS: A statistically significant, dose-dependent reduction was detected in the severity and frequency of symptoms in seropositive but not seronegative patients. The severity of abdominal pain and bloating was reduced by 58 and 44%, respectively, in the cohort receiving the highest latiglutenase dose (900 mg, n = 14) relative to placebo (n = 54). Symptom improvement increased from week 6 to week 12. There was also a trend toward greater symptom improvement with greater baseline symptom severity. CONCLUSIONS: Seropositive CD patients show symptomatic improvement from latiglutenase taken with meals and would benefit from the availability of this treatment.

Symptoms of Functional Intestinal Disorders Are Common in Patients with Celiac Disease Following Transition to a Gluten-Free Diet.

BACKGROUND: Celiac disease and functional intestinal disorders may overlap, yet the natural history of functional symptoms in patients with celiac disease is unknown. AIM: To investigate the prevalence of irritable bowel syndrome (IBS), functional dyspepsia (FD), and functional bloating (FB) symptoms among patients with celiac disease at diagnosis and during the first year of a gluten-free diet. METHODS: Adults with a new diagnosis of celiac disease were surveyed at baseline, 6 months and 1 year using standardized measures for intestinal symptoms [Rome III diagnostic questionnaire and celiac symptom index (CSI)] and gluten-free diet adherence [gluten-free eating assessment tool (GF-EAT) and celiac diet adherence test]. RESULTS: At diagnosis, two-thirds fulfilled Rome III diagnostic questionnaire symptom criteria for IBS (52%), functional dyspepsia (27%), and/or functional bloating (9%). One year post-diagnosis, there was high adherence to a gluten-free diet as 93% reported gluten exposure less than once per month on the GF-EAT and only 8% had ongoing celiac disease symptoms (CSI score >45). The rates of those meeting IBS (22%) and functional dyspepsia (8%) symptom criteria both decreased significantly on a gluten-free diet. The prevalence of functional symptoms (any of IBS, FD or FB) at 1 year was 47%. CONCLUSIONS: Long-term follow-up of patients with celiac disease is necessary because many patients with celiac disease who are adherent to a gluten-free diet have persistent gastrointestinal symptoms.

Obesity, Metabolic Syndrome, and Cardiovascular Risk in Gluten-Free Followers Without Celiac Disease in the United States: Results from the National Health and Nutrition Examination Survey 2009-2014.

BACKGROUND: Despite unclear benefits of gluten-free diets (GFD) in the general population, gluten-free followers without medical indications are driving the market. Few studies have investigated health benefits of GFD in the general population. AIMS: To estimate metabolic and cardiovascular disease (CVD) risk profiles among gluten-free followers without celiac disease (CD). METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. There were 13,523 persons without CD who had GFD information. People with known CVD were excluded. We compared gluten-free followers without CD and the general population by selective metabolic and CVD risk profiles using survey-weighted generalized logistic regression. RESULTS: There were 155 gluten-free followers without CD and CVD, corresponding to a weighted prevalence of 1.3% (3.2 million Americans). Gluten-free followers tended to be women and have a smaller waist circumference and higher HDL cholesterol. They also had a lower BMI with a borderline p value (0.053) and significant self-reported weight loss (-1.33 kg) over one year. Moreover, gluten-free followers were more likely to consider their weight appropriate. There was no statistical difference by age, smoking, hypertension, total cholesterol, triglyceride cholesterol, HbA1c, or fasting glucose. Despite a lower probability of having metabolic syndrome (33.0 vs 38.5%) and lower 10-year CVD risk score (4.52 vs 5.70%) in gluten-free followers, there was no statistical difference. CONCLUSIONS: Although being on a GFD may be beneficial in weight management, there was no significant difference in terms of prevalence of metabolic syndrome and CVD risk score in gluten-free followers without CD.

Tempters and Gluten-Free Diet.

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Trends and racial/ethnic disparities in gluten-sensitive problems in the United States: findings from the National Health and Nutrition Examination Surveys from 1988 to 2012.

OBJECTIVES: Racial disparities in the prevalence of celiac disease (CD) and the number of people without CD avoiding gluten (PWAG) in the United States are unknown. We aimed to describe racial differences in the prevalence of CD and PWAG, and evaluate the trends of CD in the noninstitutionalized civilian adult population of the US between 1988 and 2012. METHODS: A population-based cross-sectional study was conducted using data from the National Health and Nutrition Examination Surveys (NHANES) from 1988 to 1994, 1999 to 2004, and 2009 to 2012. Serum samples from the NHANES participants were tested for CD serology, which included IgA tissue transglutaminase (tTG IgA) and, if findings were abnormal, for IgA endomysial antibodies. Information about adherence to a gluten-free diet was obtained by means of an interviewer-administered questionnaire. RESULTS: In NHANES 2009-2012, the adjusted prevalence of CD was significantly higher (P<0.0001) among non-Hispanic whites (1.0%) than among non-Hispanic blacks (0.2%) and Hispanics (0.3%), whereas the adjusted prevalence of PWAG was significantly higher (P=0.01) in blacks (1.2%) as compared with Hispanics (0.5%) and whites (0.7%). The seroprevalence of CD in adults aged 50 years and older increased from 0.17% (95% confidence interval (CI) 0.03-0.33) in 1988-1994 to 0.44% (95% CI 0.24-0.81) in 2009-2012 (P<0.05). CONCLUSIONS: The overall prevalence of CD increased between 1988 and 2012 and is significantly more common in whites. In addition, a higher proportion of individuals maintaining a gluten-free diet in the absence of a diagnosis of CD are blacks.

The rise and fall of gluten!

Mankind has existed for 2·5 million years but only in the last 10,000 years have we been exposed to wheat. Wheat was first cultivated in the Fertile Crescent (South Western Asia) with a farming expansion that lasted from about 9000BC to 4000BC. Thus it could be considered that wheat (and gluten) is a novel introduction to man's diet! Prior to 1939 the rationing system had already been devised. This led to an imperative to try to increase agricultural production. Thus it was agreed in 1941 that there was a need to establish a Nutrition Society. The very roots of the society were geared towards necessarily increasing the production of wheat. This goal was achieved and by the end of the 20th century, global wheat output had expanded 5-fold. Perhaps as a result the epidemiology of coeliac disease (CD) or gluten sensitive enteropathy has changed. CD is a state of heightened immunological responsiveness to ingested gluten in genetically susceptible individuals. CD now affects 1 % or more of all adults, for which the treatment is a strict lifelong gluten-free diet. However, there is a growing body of evidence to show that a far greater proportion of individuals without coeliac disease are taking a gluten-free diet of their own volition. This clinical entity has been termed non-coeliac gluten sensitivity (NCGS), although the condition is fraught with complexities due to overlap with other gluten-based constituents that can also trigger similar clinical symptoms. This review will explore the relationship between gluten, the rising prevalence of modern coeliac disease, and the new entity of NCGS along with its associated uncertainties.

Transglutaminase 6 antibodies in the diagnosis of gluten ataxia.

OBJECTIVES: The previous finding of an immunologic response primarily directed against transglutaminase (TG)6 in patients with gluten ataxia (GA) led us to investigate the role of TG6 antibodies in diagnosing GA. METHODS: This was a prospective cohort study. We recruited patients from the ataxia, gluten/neurology, celiac disease (CD), and movement disorder clinics based at Royal Hallamshire Hospital (Sheffield, UK) and the CD clinic, Tampere University Hospital (Tampere, Finland). The groups included patients with idiopathic sporadic ataxia, GA, and CD, and neurology and healthy controls. All were tested for TG6 antibodies. Duodenal biopsies were performed in patients with positive serology. In addition, biopsies from 15 consecutive patients with idiopathic sporadic ataxia and negative serology for gluten-related disorders were analyzed for immunoglobulin A deposits against TG. RESULTS: The prevalence of TG6 antibodies was 21 of 65 (32%) in idiopathic sporadic ataxia, 35 of 48 (73%) in GA, 16 of 50 (32%) in CD, 4 of 82 (5%) in neurology controls, and 2 of 57 (4%) in healthy controls. Forty-two percent of patients with GA had enteropathy as did 51% of patients with ataxia and TG6 antibodies. Five of 15 consecutive patients with idiopathic sporadic ataxia had immunoglobulin A deposits against TG2, 4 of which subsequently tested positive for TG6 antibodies. After 1 year of gluten-free diet, TG6 antibody titers were significantly reduced or undetectable. CONCLUSIONS: Antibodies against TG6 are gluten-dependent and appear to be a sensitive and specific marker of GA.

Functional replacements for gluten.

Celiac disease (CD) is an immune-mediated disease triggered in genetically susceptible individuals by ingested gluten from wheat, rye, barley, and other closely related cereal grains. Currently, the only therapy able to normalize the clinical and histological manifestation of the disease is a strict and life-long gluten-free (GF) diet. The replacement of gluten presents a significant technological challenge, as it is an essential structure-building protein, which is necessary for formulating high-quality baked goods. The objective of this paper is to review some basics about CD, its current prevalence, and the recent advances in the preparation of high-quality GF breads using GF flours, starches, hydrocolloids, gums, and novel functional ingredients and technologies.

Diet in dermatology: revisited.

Diet has an important role to play in many skin disorders, and dermatologists are frequently faced with the difficulty of separating myth from fact when it comes to dietary advice for their patients. Patients in India are often anxious about what foods to consume, and what to avoid, in the hope that, no matter how impractical or difficult this may be, following this dictum will cure their disease. There are certain disorders where one or more components in food are central to the pathogenesis, e.g. dermatitis herpetiformis, wherein dietary restrictions constitute the cornerstone of treatment. A brief list, although not comprehensive, of other disorders where diet may have a role to play includes atopic dermatitis, acne vulgaris, psoriasis vulgaris, pemphigus, urticaria, pruritus, allergic contact dermatitis, fish odor syndrome, toxic oil syndrome, fixed drug eruption, genetic and metabolic disorders (phenylketonuria, tyrosinemia, homocystinuria, galactosemia, Refsum's disease, G6PD deficiency, xanthomas, gout and porphyria), nutritional deficiency disorders (kwashiorkar, marasmus, phrynoderma, pellagra, scurvy, acrodermatitis enteropathica, carotenemia and lycopenemia) and miscellaneous disorders such as vitiligo, aphthous ulcers, cutaneous vasculitis and telogen effluvium. From a practical point of view, it will be useful for the dermatologist to keep some dietary information handy to deal with the occasional patient who does not seem to respond in spite of the best, scientific and evidence-based therapy.