Gluten Withdrawal Research Articles

Gluten and Wheat in Women's Health: Beyond the Gut.

Since the rise of awareness of gluten/wheat-related disorders in the academic and clinical field in the last few decades, misinformation regarding the gluten-free diet (GFD) and its impact on health has been spreading among the general population. Despite the established link between gluten and celiac disease (CD), where a GFD is mandatory to reach clinical and histological remission, things are more complicated when it comes to non-celiac gluten/wheat sensitivity (NCGWS) and other autoimmune/dysimmune disorders. In the last conditions, a beneficial effect of gluten withdrawal has not been properly assessed, but still is often suggested without strong supporting evidence. In this context, women have always been exposed, more than men, to higher social pressure related to nutritional behaviors and greater engagement in controlling body weight. With this narrative review, we aim to summarize current evidence on the adherence to a GFD, with particular attention to the impact on women's health.

More Than Three Years for Normalisation of Routine Laboratory Values after Gluten Withdrawal in Paediatric Coeliac Patients.

We performed a retrospective case-control study in Spanish paediatric patients, including 21 celiac patients and 20 healthy controls. The 21 patients selected in the case-control study were followed for 5 years after starting a gluten-free diet (GFD). All patients had type 3 villous atrophy according to the Marsh-Oberhuber classification. A total of 39 blood samples were taken before the start of the GFD, and 109 were taken after. Twenty control sera from healthy donors were used for comparison. We found that patients had a subclinical but statistically significant increase in blood calcium, transaminases, and white blood cells, and a decrease in serum iron, at the time of diagnosis. Our study also shows that analytical values normalise within five years on a gluten-free diet. The use of a combination of subclinical changes, including low iron, high calcium, elevated leukocytes, lymphocytes, and ALT levels in blood samples, together with a low growth percentile, is pertinent in detecting coeliac disease. This set of parameters could help in the diagnosis of patients without clinical symptoms. We can also show that the levels of Fe, Ca, transaminases, and leucocytes remain subclinically altered after 3 years, despite the gluten-free diet.

Assessing the Prevalence of HLA-DQ2 and HLA-DQ8 in Lipedema Patients and the Potential Benefits of a Gluten-Free Diet.

Objective The aim of this study is to assess the prevalence of HLA-DQ2 and HLA-DQ8 in women diagnosed with lipedema. Methods Leukocyte histocompatibility antigen (HLA) tests of 95 women diagnosed with lipedema were analyzed using non-probabilistic sampling for convenience. The prevalence of HLA-DQ2 and HLA-DQ8 was compared to the general population. Results The prevalence of HLA-DQ2+ was 47.4%, that of HLA-DQ8+ was 22.2%, the presence of any celiac disease associated HLA (HLA-DQ2+ or HLA-DQ8+) was 61.1%, both HLA (HLA-DQ2+ and HLA-DQ8+) was 7.4%, and the absence of celiac disease associated HLA was 39%. Compared to the general population, there was a significantly higher prevalence of HLA-DQ2, HLA-DQ8, any HLA, and both HLAs in lipedema patients. The mean weight of patients with HLA-DQ2+ was significantly lower than the overall study population, and their mean BMI significantly differed from the overall mean BMI. Conclusion Lipedema patients seeking medical assistance have a higher prevalence of HLA-DQ2 and HLA-DQ8. Considering the role of gluten in inflammation, further research is needed to establish if this association supports the benefit of gluten withdrawal from the diet in managing lipedema symptoms.

Should Rheumatoid Arthritis Patients go on a Gluten-Free Diet?

Rheumatoid arthritis and celiac disease are autoimmune inflammatory diseases that share multiple aspects. The only established therapy for celiac disease is the gluten-free diet. The current therapy for rheumatic arthritis patients is mainly pharmaceutical and physiotherapy. The nutritional therapy is in its first steps, while several diets were suggested. A gluten-free diet was preliminarily assessed with some beneficial effects; however, no guidelines exist in the rheumatic, nutritional, nor in autoimmune literature. The present review expends on rheumatoid arthritis - celiac disease relationship, on the gut-joint axis, on the enteric luminal and mucosal eco events in rheumatoid arthritis patients. Various aspects of Gluten-free diet are reported, guidelines for gluten withdrawal are suggested and the beneficial aspects of Gluten-free-Mediterranean diet are described.

Flow cytometric analysis of duodenal intraepithelial lymphocytes (celiac lymphogram): A diagnostic test for celiac disease.

Celiac disease (CD) diagnosis in adults and certain cases of children mainly relies on the assessment of histopathological features in duodenal biopsies. However, none of the histological findings that characterize CD are pathognomonic. This, in addition to the clinical heterogeneity of the disease and the presence of seronegative forms, makes the diagnosis of CD still a challenge. A hallmark of the celiac mucosa is the elevated number of TCRγδ intraepithelial lymphocytes (IEL) in the epithelium, which may remain increased even long after gluten withdrawal. Active disease is also characterized by the decreased CD3- IEL subset. The use of flow cytometry enables a precise cell counting and phenotyping, allowing the ascertainment of both TCRγδ+ and CD3- IEL subsets, what is known as the "IEL lymphogram." Although determination of this lymphogram has become a routine evaluation tool in numerous hospitals, standardization of the technical method will guarantee an accurate performance in order to become a pivotal technique for CD diagnosis. Here we describe the protocol to process duodenal biopsies in order to obtain the IELs from the mucosa and to characterize lymphocyte populations by flow cytometry to obtain the IEL lymphogram.

Diagnostic management of patients reporting symptoms after wheat ingestion.

Many patients report symptoms after wheat ingestion experiencing a wide spectrum of clinical manifestations. Three possible diagnoses have been recognized: celiac disease (CD), wheat allergy (WA), and non-celiac (gluten) wheat sensitivity (NCGS/NCWS). CD is a chronic immune-mediated disease of the small bowel caused by exposure to dietary gluten in genetically predisposed individuals, with a prevalence of approximately 1%. It is characterized by mucosal inflammation and atrophy following exposure to gluten and improvement after gluten withdrawal. Food allergies are immunological responses to a food antigen. WA is the expression of an immunologically mediated process that can be immunoglobulin E (IgE) or non-IgE mediated; its many symptoms include urticaria/angioedema, asthma, rhinitis, and anaphylaxis. NCGS/NCWS is characterized by gastrointestinal and/or extra-intestinal symptoms after ingestion of gluten-containing food in subjects not affected by CD or WA. The aim of this review is to help physicians and nutritionists diagnose the cause of symptoms reported after wheat ingestion, thus avoiding patient frustration, inappropriate testing, and incorrect or missed diagnoses. An algorithm for the diagnostic approach in these patients is provided, to help to diagnose CD, WA, NCGS/NCWS or to identify possible functional disorders as the wheat-sensitive irritable bowel syndrome. A personalized approach, regular follow-up, and the help of a skilled healthcare professional are mandatory for patients with symptoms following wheat ingestion is provided. A gluten-free-diet is often recommended for patients with self-reported gluten/wheat-dependent symptoms; for patients with symptoms similar to those of functional diseases while there is evidence that a low-FODMAP diet could be the first option.

Celiac Disease.

Celiac Disease.

Gluten-free diet can ameliorate the symptoms of non-celiac autoimmune diseases.

A gluten-free diet (GFD) is the recommended treatment for gluten-dependent disease. In addition, gluten withdrawal is popular and occasionally is suggested as a treatment for other autoimmune diseases (ADs). The current systematic review summarizes those entities and discusses the logic behind using a GFD in classical non-gluten-dependentADs. A search for medical articles in PubMed/MEDLINE, Web of Sciences, LILACS, and Scielo published between 1960 and 2020 was conducted, using the key words for various ADs and GFDs. Eight-three articles were included in the systematic review (using PRISMA guidelines). Reduction in symptoms of ADs after observance of a GFD was observed in 911 out of 1408 patients (64.7%) and in 66 out of the 83 selected studies (79.5%). The age of the patients ranged from 9 months to 69 years. The duration of the GFD varied from 1 month to 9 years. A GFD can suppress several harmful intraluminal intestinal events. Potential mechanisms and pathways for the action of GFD in the gut - remote organs' axis have been suggested. A GFD might represent a novel nutritional therapeutic strategy for classical non-gluten-dependent autoimmune conditions.

Non-Celiac Gluten Sensitivity in Children: Controversial Role of Gluten and Diagnostic Enigma

Non-celiac gluten sensitivity (NCGS) is a debatable condition that affects less than 6% of children. The absence of specific diagnostic markers and standardized diagnostic procedures make the diagnosis of NCGS challenging, covering patients with different and varied symptoms. Generally, the parents of small and younger children introduce a gluten-free diet (GFD) based on their personal experiences and expectations. Additionally, a “fad component” exists, contributing to the recent rise in the popularity of GFD. Thus, celiac disease (CD) and wheat allergy (WA) must be excluded as these also appear in individuals experiencing symptoms similar to those of NCGS, improving and worsening with gluten withdrawal and consumption, respectively. The role of gluten inducing gastrointestinal symptoms in individuals with self-reported NCGS has been skeptically assessed based on evidence in recent years. However, currently, it is unknown whether a strict GFD is necessary for patients with NCGS. Thus, the placebo-controlled gluten challenge remains the gold standard for a challenging diagnosis like NCGS. The present review evaluates the published studies based largely on the adult population and describes the key elements in diagnosing NCGS and differential diagnosis with CD and WA.

Probiotic supplement and gluten withdrawal in gluten allergy Patients may lead to gluten tolerance: first case report

Probiotic species such as lactobacillus and bifidobacteria are known to have a major role in gluten digestion and regulation of proper functioning of gastrointestinal system however these are found to be missing in gluten allergy patients. So, here in this case we aimed to find the effect of probiotic supplementation along with gluten free diet in celiac disease patient. A case of an 8-year-old female child admitted to civil hospital, Faridkot with chief complaints of vomiting, diarrhea, weight loss, retarded growth, and malnutrition was studied. When she first visited the hospital, based on her symptoms, she was advised celiac disease workup and was found to be highly tTG IgA positive (10.62). The subject was shifted to a strict gluten free diet along with probiotic supplementation. The subject was regularly followed up for the period of four and half years in order to find improvement in her symptoms. After 4 years, gluten diet was gradually reintroduced in a phased manner; the patient remained well even on full gluten diet. This may be due to probiotic supplementation to the subject along with gluten free diet. Present case report describes the spontaneous recovery of celiac disease patient after strict adherence to gluten free diet and probiotic supplementation for a specified period. It is suggested that there should be a proper monitoring and detailed evaluation of clinical and histological markers of recovery in a patient after strict adherence to gluten free diet and probiotic supplementation in order to evaluate the possible role of probiotic supplements in the management of CD.

P029 Idiopathic inflammatory myopathy and axonal peripheral polyneuropathy in a poorly controlled coeliac disease patient

Background/Aims The current mainstay treatment of idiopathic inflammatory myopathies (IIM) includes steroid therapy with treatment escalation to steroids -sparing immunosuppressants to maintain remission. Nevertheless, some patients may not fully recover to their normal muscle strength, while exposing to potential side effects of these drugs. We report the first case of IIM and axonal peripheral polyneuropathy in a poorly controlled coeliac patient, who made complete recovery with adherence to gluten-free diet. Methods A 76-year-old white Caucasian lady, who was previously independent, presented with 6-weeks history of pain and weakness in both legs. She required the use of a wheelchair to get around as she was unable to weight bear as the result of the pain. She denied any change to regular medications, history of trauma, new rash, joint swelling, or B-symptoms. There was no history of smoking, alcohol, statins, or steroid use. She was previously diagnosed with coeliac disease 10 years ago but had opted not to adhere to a gluten-free diet due to personal preference. Results On examination, there was significant muscle tenderness on palpation of bilateral lower limbs. The rest of systemic examination was unremarkable. Duodenal biopsy revealed severe villous atrophy and chronic lymphocytic and plasma cell inflammation, which reinforced the diagnosis of coeliac disease. All immunology screen including ANA, ENA, ds-DNA, myositis and vasculitis screen were negative except anti-RO-52. This patient did not have any clinical feature of Sjogren’s or systemic lupus erythematosus. EMG revealed fibrillation potentials, positive sharp waves, and myotonic discharges in the paraspinal, upper and lower limbs muscles. It also demonstrated underlying axonal peripheral polyneuropathy. Muscle biopsy showed features consistent with the diagnosis of idiopathic inflammatory myopathy. This patient was started on a gluten-free diet during admission. Interestingly, we discovered that her creatinine kinase level had improved spontaneously along with the clinical improvement of her presenting symptoms. As her symptoms have completely resolved, she was discharged home. She was never started on steroid or immunosuppressant due to her significant clinical improvement. At three-month follow up, her creatinine kinase level had normalised, and she remained in remission while adhering to a gluten-free diet. Conclusion To the best of our knowledge, there is no reported case of complete clinical resolution of IIM with gluten withdrawal in coeliac disease patients, without the need of steroid or immunosuppressants. In addition, the concomitant of myopathy and polyneuropathy, as some described as neuromyositis, is extremely rare. The pathophysiology remains unclear; however, it is proposed that neuropathy could be an extra-muscular manifestation of IIM.The clinical remission of IIM in our patient with adherence to a gluten-free diet provide an alternative treatment option to the current recommended regimes of steroid and immunosuppressants. Such non-pharmacological approach is favourable, especially in the current SARS-CoV-2 pandemic. Disclosure Y. Tan: None. A. Mohamedalhadi: None. F. Wood: None.

FORMULATION OF GLUTEN-FREE BREAD WITH DIFFERENT LEVELS OF HYDROXYPROPYL METHYLCELLULOSE, RAW BANANA FLOUR AND PROOF TIME: MODELLING, PROXIMATE AND SENSORY ANALYSES

Semi-urbanization has increased the demand of bakery products triggering variousgluten-related disorders including Celiac Disease (CD), Non-celiac Gluten Sensitivity (NCGS), Gluten Ataxia and Wheat Allergy. Among these, CD accounts for nearly 1-2%global population. Gluten withdrawal- cornerstone treatment for CD is a bumpy road with nutritional deficiencies and poor quality of life. Additionally, there is a surge of people intentionally avoiding gluten for various reasons. The present work intends to optimize a formula for a gluten free (GF) bread and determine the effect of prooftime, hydroxypropyl methylcellulose (HPMC) and raw banana flour at different levels on moisture content, bake loss, specific volume, texture parameters andcrust-crumb brightness (L*) using response surface methodology (RSM) based on central composite rotatable design (CCRD).The results revealed moisture content, hardness, springiness, resilience and crust-crumb L*were significantly affected. Different proof time levels altered moisture content, bake loss and colour parameters with no influence on textural parameters. Increasing levels of HPMC impeded bake loss and crumb lightness but exacerbated hardness. Nonetheless, on its interaction with raw banana flour, there was antagonistic effect on hardness. Addition of raw banana flour darkened the bread. Thus, optimal conditions (HPMC 2%, raw banana flour 37.16% and proof time 40mins) were appliedto produce good quality bread. Furthermore, sensory and proximateanalyses of optimum GF bread were compared to whole wheat bread depicting higherprotein-fat content, lower carbohydrate content and overall acceptability score of 7.88for the former; the demand for which is steadily and incessantly expanding

Persistent Skin Symptoms after Diagnosis and on a Long-term Gluten-free Diet in Dermatitis Herpetiformis.

Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease treated with a gluten-free diet. However, the itching and blistering rash alleviates slowly after gluten withdrawal and occasionally persists despite a long-term gluten-free diet. This study investigated the prevalence and factors associated with prolonged (i.e. > 2 years) and ongoing skin symptoms in 237 patients with dermatitis herpetiformis. Data were gathered from medical records and via questionnaires. Among patients with dermatitis herpetiformis, 38% had prolonged symptoms after diagnosis, and 14% had ongoing skin symptoms at follow-up (median duration of gluten-free diet 24 years). A severe rash at diagnosis was associated with both prolonged and ongoing cutaneous symptoms. In addition, patients with dermatitis herpetiformis with ongoing skin symptoms at follow-up had been on the dietary treatment for a shorter time (median duration 16 vs 25 years) and were less often on a strict diet (53% vs 78%) compared with patients with dermatitis herpetiformis without ongoing skin symptoms.

Celiac disease in the COVID-19 pandemic

BackgroundThe COVID-19 pandemic has had an impact on global health. DesignThe impact of the COVID-19 pandemic on patients with coeliac disease was assessed in the present review. ResultsThe incidence of coeliac disease and the problems associated with coeliac disease increased during the COVID-19 pandemic. Adherence to the diet is crucial for the patient's health and quality of life since the only approved therapy for coeliac disease is a gluten withdrawal. ConclusionsA gluten-free diet should be promoted by the therapeutic team and implemented among these categories of patients.

Navigating the Gluten-Free Boom: The Dark Side of Gluten Free Diet

In gluten dependent conditions the gluten free diet is the cornerstone of therapy, decreasing disease activity, improving health and quality of life and treating or preventing the associated complications. Gluten withdrawal implies strict and lifelong elimination not only of wheat, barley, rye, and wheat-contaminated oats, but also of numerous non-nutritional products where components of wheat are often added. Due to multiple reasons the diet is difficult to follow and the long-term adherence is decreased with time. The present review summarizes the dark side of gluten restriction where nutritional deficiencies, toxicity, morbidity, mortality, and mental health problems are reported. The aim being to increase awareness, avoid, detect and treat the side effects and to promote a healthier nutrition, for the patient's benefits.

European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders.

This guideline presents recommendations for the management of coeliac disease (CD) and other gluten-related disorders both in adults and children. There has been a substantial increase in the prevalence of CD over the last 50 years and many patients remain undiagnosed. Diagnostic testing, including serology and biopsy, should be performed on a gluten-containing diet. The diagnosis of CD is based on a combination of clinical, serological and histopathological data. In a group of children the diagnosis may be made without biopsy if strict criteria are available. The treatment for CD is primarily a gluten-free diet (GFD), which requires significant patient education, motivation and follow-up. Slow-responsiveness occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms necessitate a review of the original diagnosis, exclude alternative diagnoses, confirm dietary adherence (dietary review and serology) and follow-up biopsy. In addition, evaluation to exclude complications of CD, such as refractory CD or lymphoma, should be performed. The guideline also deals with other gluten-related disorders, such as dermatitis herpetiformis, which is a cutaneous manifestation of CD characterized by granular IgA deposits in the dermal papillae. The skin lesions clear with gluten withdrawal. Also, less well-defined conditions such as non-coeliac gluten sensitivity (NCGS) and gluten-sensitive neurological manifestations, such as ataxia, have been addressed. Newer therapeutic modalities for CD are being studied in clinical trials but are not yet approved for use in practice.

The value of a biopsy in celiac disease follow up: assessment of the small bowel after 6 and 24 months treatment with a gluten free diet.

a routine small bowel biopsy (SBB) during the follow up of celiac disease (CD) is controversial. Little information is available regarding the histological changes during (gluten free diet (GFD) in the long term. the aim of the study was to evaluate a novel criterion to compare duodenal histology in CD patients after six months and two years of gluten withdrawal. this was a cross-sectional study of 200 patients with confirmed Marsh I-III who were under the six months (group A, n = 100) and 24 months (group B, n = 100) of a GFD. Nineteen patients were excluded due to an inadequate adherence to the GFD and another 23 patients were excluded as they were unwilling to undergo a re-endoscopy and did not comply with the necessary criteria. Endoscopy with a duodenal biopsy, serological assays and clinical evaluation were performed and compared with baseline data in the remaining 58 patients (20 patients in group A and 38 patients in group B). a significant complete histological recovery was found in 47.4% of patients in group B compared to 30% in group A (p = 0.026). A partial histological recovery was reported in seven (35%) and eleven (28.9%) patients in groups A and B, respectively. Any changes in mucosal histology after GFD was observed in 35% of patients in group A and 23.7% in group B. Serological assessment and endoscopic appearance normalized in 78.9% vs 75.0% in group B and 68.4% vs 65.0% in group A, respectively. However, this improvement did not reach statistical significance (p > 0.05). the results of this study show that histological recovery in patients with Marsh ≥ III is slow and does not correlate with symptomatic improvement. We suggest that the long-term effects of a GFD can play an important role in achieving histological improvement, especially in older patients.

Recent advances in understanding non-celiac gluten sensitivity

Non-celiac gluten sensitivity (NCGS) is a condition characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing foods in the absence of celiac disease and wheat allergy. The diagnosis is cumbersome and currently confirmed only by gluten withdrawal and double-blind placebo challenge protocols. There is great overlap in symptoms between NCGS and other functional gastrointestinal disorders, making a differential diagnosis difficult. The pathophysiology of NCGS is largely unclear, and there are contrasting data on the trigger of this condition. This review will highlight the state-of-the-art knowledge on NCGS and the key open questions.

26. Correlation of ultrasonography and hepatobiliary scintigraphy for incidence of gall bladder dysfunction in children with celiac disease at presentation and post gluten withdrawal

26. Correlation of ultrasonography and hepatobiliary scintigraphy for incidence of gall bladder dysfunction in children with celiac disease at presentation and post gluten withdrawal

Vaccine Immunotherapy for Celiac Disease.

Autoimmune and allergic disorders are highly prevalent conditions in which an altered or abnormal immune response is mounted against self- or environmental antigens, respectively. Antigen-based immunotherapy is a therapeutic option aimed at restoring the specific immune tolerance toward pathogenic antigens while leaving the rest of the immune system unaffected. This strategy proved efficacy especially in allergic diseases, including asthma, allergic rhinitis, and food allergies, but still has shortcomings for the treatment of autoimmune diseases. However, there are no available therapies, currently, in clinical practice for restoring the physiological tolerance that is typically lost in autoimmune diseases. In celiac disease, which is a common immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals, antigen-based immunotherapy could be a feasible option thanks to our deep understanding of the pathogenic mechanisms underpinning this condition. In fact, the immunodominant gluten epitopes are well-characterized and are recognized by pathogenic CD4+ T-cells that could be desensitized with immunotherapy. Moreover, the intestinal damage occurring in celiac disease (i.e., villous atrophy) is reversible upon gluten withdrawal. Only recently the results of a phase I trial of an intradermal, adjuvant-free, formulation of three specific gluten peptides (Nexvax2) showed a good safety profile, albeit its efficacy still needs to be demonstrated. More results are awaited, as they may radically change patients' quality of life that is constrained by the lifelong gluten-free diet and by the potential onset of life-threatening complications.