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Guidelines for best practices in monitoring established coeliac disease in adult patients.
Elli, L, Leffler, D, Cellier, C, Lebwohl, B, Ciacci, C, Schumann, M, Lundin, KEA, Chetcuti Zammit, S, Sidhu, R, Roncoroni, L, et al
Nature reviews. Gastroenterology & hepatology. 2024;(3):198-215
Abstract
Coeliac disease (CeD) is an immunological disease triggered by the consumption of gluten contained in food in individuals with a genetic predisposition. Diagnosis is based on the presence of small bowel mucosal atrophy and circulating autoantibodies (anti-type 2 transglutaminase antibodies). After diagnosis, patients follow a strict, life-long gluten-free diet. Although the criteria for diagnosis of this disease are well defined, the monitoring phase has been studied less and there is a lack of specific guidelines for this phase. To develop a set of clinical guidelines for CeD monitoring, we followed the Grading of Recommendations Assessment, Development and Evaluation methodology. Statements and recommendations with the level of evidence were developed and approved by the working group, which comprised gastroenterologists, pathologists, dieticians and biostatisticians. The proposed guidelines, endorsed by the North American and European coeliac disease scientific societies, make recommendations for best practices in monitoring patients with CeD based on the available evidence. The evidence level is low for many topics, suggesting that further research in specific aspects of CeD would be valuable. In conclusion, the present guidelines support clinicians in improving CeD treatment and follow-up and highlight novel issues that should be considered in future studies.
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2.
Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis.
Shiha, MG, Nandi, N, Raju, SA, Wild, G, Cross, SS, Singh, P, Elli, L, Makharia, GK, Sanders, DS, Penny, HA
Gastroenterology. 2024;(4):620-630
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Abstract
BACKGROUND & AIMS Current international guidelines recommend duodenal biopsies to confirm the diagnosis of celiac disease in adult patients. However, growing evidence suggests that immunoglobulin A (IgA) anti-tissue transglutaminase (tTg) antibody levels ≥10 times the upper limit of normal (ULN) can accurately predict celiac disease, eliminating the need for biopsy. We performed a systematic review and meta-analysis to evaluate the accuracy of the no-biopsy approach to confirm the diagnosis of celiac disease in adults. METHODS We systematically searched MEDLINE, EMBASE, Cochrane Library, and Web of Science from January 1998 to October 2023 for studies reporting the sensitivity and specificity of IgA-tTG ≥10×ULN against duodenal biopsies (Marsh grade ≥2) in adults with suspected celiac disease. We used a bivariate random effects model to calculate the summary estimates of sensitivity, specificity, and positive and negative likelihood ratios. The positive and negative likelihood ratios were used to calculate the positive predictive value of the no-biopsy approach across different pretest probabilities of celiac disease. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. This study was registered with PROSPERO, number CRD42023398812. RESULTS A total of 18 studies comprising 12,103 participants from 15 countries were included. The pooled prevalence of biopsy-proven celiac disease in the included studies was 62% (95% confidence interval [CI], 40%-83%). The proportion of patients with IgA-tTG ≥10×ULN was 32% (95% CI, 24%-40%). The summary sensitivity of IgA-tTG ≥10×ULN was 51% (95% CI, 42%-60%), and the summary specificity was 100% (95% CI, 98%-100%). The area under the summary receiver operating characteristic curve was 0.83 (95% CI, 0.77 - 0.89). The positive predictive value of the no-biopsy approach to identify patients with celiac disease was 65%, 88%, 95%, and 99% if celiac disease prevalence was 1%, 4%, 10%, and 40%, respectively. Between-study heterogeneity was moderate (I2 =30.3%), and additional sensitivity analyses did not significantly alter our findings. Only 1 study had a low risk of bias across all domains. CONCLUSION The results of this meta-analysis suggest that selected adult patients with IgA-tTG ≥10×ULN and a moderate to high pretest probability of celiac disease could be diagnosed without undergoing invasive endoscopy and duodenal biopsy.
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Updates in the diagnosis and management of coeliac disease.
Shiha, MG, Chetcuti Zammit, S, Elli, L, Sanders, DS, Sidhu, R
Best practice & research. Clinical gastroenterology. 2023;:101843
Abstract
Coeliac disease is a common autoimmune disorder induced by ingesting gluten, the protein component of wheat, barley, and rye. It is estimated that one-in-hundred people worldwide have coeliac disease, of whom the majority remain undiagnosed. Coeliac disease is characterized by a wide range of gastrointestinal and extraintestinal symptoms but can also present asymptomatically. Diagnosing coeliac disease depends on the concordance of clinical, serological and histopathological data. However, the diagnosis can be challenging and frequently overlooked. Undiagnosed coeliac disease is associated with an increased risk of complications and detrimental effects on quality of life. Early diagnosis and treatment of coeliac disease are necessary to reduce the risk of long-term complications.
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Diagnostic delay in adult coeliac disease: An Italian multicentre study.
Lenti, MV, Aronico, N, Bianchi, PI, D'Agate, CC, Neri, M, Volta, U, Mumolo, MG, Astegiano, M, Calabrò, AS, Zingone, F, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2023;(6):743-750
Abstract
BACKGROUND There are few data regarding the diagnostic delay and its predisposing factors in coeliac disease (CD). AIMS To investigate the overall, the patient-dependant, and the physician-dependant diagnostic delays in CD. METHODS CD adult patients were retrospectively enroled at 19 Italian CD outpatient clinics (2011-2021). Overall, patient-dependant, and physician-dependant diagnostic delays were assessed. Extreme diagnostic, i.e., lying above the third quartile of our population, was also analysed. Multivariable regression models for factors affecting the delay were fitted. RESULTS Overall, 2362 CD patients (median age at diagnosis 38 years, IQR 27-46; M:F ratio=1:3) were included. The median overall diagnostic delay was 8 months (IQR 5-14), while patient- and physician-dependant delays were 3 (IQR 2-6) and 4 (IQR 2-6) months, respectively. Previous misdiagnosis was associated with greater physician-dependant (1.076, p = 0.005) and overall (0.659, p = 0.001) diagnostic delays. Neurological symptoms (odds ratio 2.311, p = 0.005) and a previous misdiagnosis (coefficient 9.807, p = 0.000) were associated with a greater extreme physician-dependant delay. Gastrointestinal symptoms (OR 1.880, p = 0.004), neurological symptoms (OR 2.313, p = 0.042), and previous misdiagnosis (OR 4.265, p = 0.000) were associated with increased extreme overall diagnostic delay. CONCLUSION We identified some factors that hamper CD diagnosis. A proper screening strategy for CD should be implemented.
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Follow-Up of Celiac Disease in Adults: "When, What, Who, and Where".
Mulder, CJJ, Elli, L, Lebwohl, B, Makharia, GK, Rostami, K, Rubio-Tapia, A, Schumann, M, Tye-Din, J, Zeitz, J, Al-Toma, A
Nutrients. 2023;(9)
Abstract
For patients with celiac disease (CeD), a lifelong gluten-free diet is not a voluntary lifestyle choice-it is a necessity. The key end points in clinical follow-up are symptom resolution, the normalization of weight, prevention of overweight, seroconversion, and negation or minimization of increased long-term morbidity. For the latter, a surrogate endpoint is mucosal healing, which means the normalization of histology to Marsh 0-1. Ideally, celiac follow-up care includes a multidisciplinary approach, effective referral processes, improved access that leverages technological advances, and following guidelines with the identification of measurable quality indicators, ideally informed by evidence-based research. Face-to-face CeD care and telemedicine are considered the standards for this process, although published data are insufficient. Guidelines and statements on diagnosis are readily available. However, data are lacking on optimal clinic visit intervals and outcomes and quality indicators such as improvement of symptoms, function and quality of life, survival and disease control, and how to most effectively use healthcare resources. The results of future research should provide the basis for general recommendations for evidence-based standards of quality of care in CeD.
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Heavy Metal and Rice in Gluten-Free Diets: Are They a Risk?
Bascuñán, KA, Orosteguí, C, Rodríguez, JM, Roncoroni, L, Doneda, L, Elli, L, Araya, M
Nutrients. 2023;(13)
Abstract
A gluten-free diet (GFD) is the treatment of choice for gluten-related disorders. It has been associated with macro- and micronutrient deficiencies. Recently, consumption of arsenic-contaminated rice has raised concern because of the potential greater risk that it may represent for people on GFDs, whose rice consumption is high, since it is a fundamental cereal in GFDs. We reviewed the data published over the last 20 years in Medline and Scielo, in English, French and Spanish, on four metals (As, Hg, Cd, and Pb), to assess whether the evidence suggests that celiac disease or consumption of a GFD is associated with increased levels of blood/urinary metal concentrations. The review revealed a few articles that were directly related to the four metals and their relationships with a GFD. The evidence supports that rice-based products are a relevant source of As and other metals. Clinical studies and evaluations based on NHANES have indicated that persons on GFDs have higher As and Hg blood/urinary levels, suggesting that the diet and not the disease is responsible for it. The levels described are statistically significant compared to those of persons on complete diets, but far from toxic levels. The question of whether higher exposure to heavy metals associated with a GFD is biologically relevant remains unanswered and deserves study.
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Effects of a gluten challenge in patients with irritable bowel syndrome: a randomized single-blind controlled clinical trial.
Saadati, S, Sadeghi, A, Mohaghegh-Shalmani, H, Rostami-Nejad, M, Elli, L, Asadzadeh-Aghdaei, H, Rodrigo, L, Zali, MR
Scientific reports. 2022;12(1):4960
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Expert Review
Conflicts of interest:
None
Take Home Message:
- The results of this study suggest that a strict gluten-free, low FODMAP diet could be used in Individuals with IBS for anxiety reduction and improvement in quality of life.
- However, only a small number of participants were included and followed for a short duration.
- IBS is a complex disorder the cause of which is largely unknown. It requires a multidisciplinary approach in its treatment.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Irritable bowel syndrome (IBS), a functional disorder of the lower gastrointestinal tract, is characterized by various somatic and psychological manifestations. Evidence suggests IBS and non-celiac gluten sensitivity (NCGS) overlap. The development of IBS is thought to be multifactorial. Low-grade inflammation and food intolerances including to gluten and fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP), may play a role. Gluten tolerance is a major dilemma in medical practice.
The aim of this randomized controlled trial is to evaluate tolerance to gluten, anxiety and quality of life in irritable bowel syndrome (IBS). Prevalence of non-celiac gluten sensitivity (NCGS) was also reported. This trial was conducted in Tehran, Iran, in adults aged 18-80 years and with symptoms of IBS according to the ROME-IV criteria.
In informing their research question, the authors reference evidence of the efficacy of a gluten-free diet (GFD) and a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet on IBS symptoms.
One hundred and seven subjects were enrolled into phase I of the study, when a strict low-FODMAP and GFD was introduced for six weeks. Seventy subjects completed phase 1, of which twenty subjects declined to continue, leaving fifty subjects. These fifty subjects were enrolled into phase 2 and randomized into three groups (i) an unrestricted gluten diet (n=10), (ii) continuation of the low-FODMAP/GFD (n=15), and (iii) a gluten challenge group (n=25), for a further six weeks.
Reductions in bloating (3.5±2.6 to 2.5±2.1, p=0.03) and pain severity (2.9±2.8 to 2±2.2, p=0.02) were observed in the GFD, and a reduction in total VAS score (45.6±15.9 to 27.8±12.8, p=0.05) in the high-gluten group. The satiety score increased (2.3±1 to 3.8±3.1, p=0.04) in the unrestricted gluten diet group. At the end of the study, differences for pain frequency, pain severity and impact on community function were observed between the groups.
In this study, a low-FODMAP strict GFD was shown to reduce anxiety and improve the quality of life.
Clinical practice applications:
- In the gluten challenge phase of the study, between-group analysis revealed significant differences for pain and impact on community function No significant differences were found for bloating, satiety, defecation, total score, anxiety scores or quality of life between the groups. These mixed results, also found in other studies, add weight to the fact that the cause of IBS is unclear. The authors hypothesize that there may be an IBS subtype or new medical term, categorized as gluten sensitivity-IBS.
- Symptoms were evaluated but not objective outcomes, for example blood biomarkers. No aggravation of symptoms was observed in this study following the gluten challenge. Other non-gluten components of food may be responsible for IBS symptoms. Recent evidence suggests that fructans may be responsible in individuals with IBS and a low-FODMAP diet may be beneficial.
- Biopsychological factors are important to consider in the duration and severity of IBS symptoms.
- A strict GFD can come with problems, as mentioned, nutritional deficiencies, difficulty finding GF foods, high cost, altered taste, impacts on social/quality of life.
- Results were mixed, however suggest a low-FODMAP strict GFD could be a therapeutic choice for the management of IBS particularly in reducing anxiety and improving quality of life.
Considerations for future research:
- Randomized controlled trials with greater numbers of participants and longer durations assessing the impact of a low-FODMAP strict GFD in IBS, are warranted.
- Including food sensitivity/intolerance testing may be useful to distinguish which individuals might benefit from a GFD alone, a low-FODMAP diet alone or a low-FODMAP GFD.
- Small intestinal bacterial overgrowth (SIBO) testing would be of interest to understand who might benefit from a low-FODMAP diet.
- Studies assessing baseline stress levels and stress management interventions in combination with dietary interventions such as low-FODMAP GFD could be important avenues of research.
Abstract
Non-celiac gluten sensitivity (NCGS) and irritable bowel syndrome (IBS) frequently overlap. Although, gluten-free diet (GFD) and low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) improve the IBS clinical picture, many aspects remain unclear. Therefore, we designed a study to evaluate gluten tolerance, anxiety and quality of life in a specific study population. Fifty IBS patients were asked to follow a low FODMAP strict GFD for 6 weeks and were then randomly allocated to the following groups for a further 6 weeks: (A) receiving 8 g/day of gluten for 2 weeks; gluten-tolerating subjects received 16 g/day for 2 weeks and then 32 g/day for a further 2 weeks; (B) continuing to follow a low FODMAP strict GFD; and (C) receiving a gluten-containing diet. After the first 6 weeks, symptom scores significantly improved. Pain severity, bloating and total score were significantly decreased in the GFD and in the high-gluten groups, while the satiety score significantly increased in group C. Between-group analysis revealed significant differences for pain severity (p = 0.02), pain frequency (p = 0.04) and impact on community function (p = 0.02) at the end of the study. Our findings suggest that low FODMAP strict GFD could be prescribed in IBS patients and would reduce anxiety and improve the quality of life.
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Nutrition in Patients with Inflammatory Bowel Diseases: A Narrative Review.
Roncoroni, L, Gori, R, Elli, L, Tontini, GE, Doneda, L, Norsa, L, Cuomo, M, Lombardo, V, Scricciolo, A, Caprioli, F, et al
Nutrients. 2022;(4)
Abstract
Inflammatory bowel diseases (IBD) affect the gastrointestinal tract: they include Crohn's disease (CD) and ulcerative colitis (UC). Each has a different phenotypic spectrum, characterized by gastrointestinal and extra-intestinal manifestations. People living with IBD are very interested in diet, but little is known about the impact of diet on these patients; no guidelines are available yet. In this review, we analyze the dietary patterns of patients with IBD and the approach to the choices of foods both in adults and pediatric patients. Very often, IBD patients report an intentional avoidance of gluten to manage the disease; furthermore, a proportion of IBD patients believe that dairy products worsen their symptoms and that avoidance may help the disease. They have a low compliance with the Mediterranean Diet, which is considered to have potential benefits but is little used in practice. In conclusion, the review underscores the pivotal role of nutritional counselling in IBD patients, and the importance of future clinical studies to evaluate the beneficial effects of dietary recommendations in the management of IBD.
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The low-FODMAP diet and the gluten-free diet in the management of functional abdominal bloating and distension.
Pessarelli, T, Sorge, A, Elli, L, Costantino, A
Frontiers in nutrition. 2022;:1007716
Abstract
This review summarizes current knowledge on the role of low-FODMAP diet and gluten-free diet in functional abdominal bloating and distension, an emerging disorder of gut-brain interaction characterized by remarkable costs for healthcare systems and a significant impact on the patient's quality of life. Ingested food plays a key role in the pathophysiology of disorders of gut-brain interaction as up to 84% of patients with irritable bowel syndrome (IBS) report food-triggered symptoms. Potential pathogenetic mechanisms of food-related symptoms in these patients are discussed, focusing on bloating and abdominal distension. These mechanisms provide the rationale for dietary treatment in patients with functional abdominal bloating and distension. The role of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) and gluten in functional abdominal bloating and distension is examined. Current literature evaluating the efficacy of the low-FODMAP diet and the gluten-free diet in abdominal bloating and distension is analyzed. Available evidence originates mainly from studies on patients with IBS, since clinical studies on selected cohorts of patients with only functional abdominal bloating and distension have been missing to date. Promising evidence on the potential efficacy of the low-FODMAP diet in functional abdominal bloating and distension is provided by the reduction of the bloating observed in patients with IBS. Regarding the gluten-free diet, there is insufficient evidence to recommend it to reduce bloating and abdominal distension. In conclusion, this review asserts the need for a close collaboration with experts in nutrition to optimize the management of these patients and reduce the risks associated with elimination diets.
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Guidelines of the Italian societies of gastroenterology on the diagnosis and management of coeliac disease and dermatitis herpetiformis.
Zingone, F, Maimaris, S, Auricchio, R, Caio, GPI, Carroccio, A, Elli, L, Galliani, E, Montagnani, M, Valiante, F, Biagi, F
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2022;(10):1304-1319
Abstract
INTRODUCTION Coeliac disease and dermatitis herpetiformis are immune-mediated diseases triggered by the consumption of gluten in genetically predisposed individuals. These guidelines were developed to provide general practitioners, paediatricians, gastroenterologists, and other clinicians with an overview on the diagnosis, management and follow-up of coeliac patients and those with dermatitis herpetiformis. METHODS Guidelines were developed by the Italian Societies of Gastroenterology. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists and a paediatrician with expertise in this field. RESULTS These guidelines provide a practical guidance for the diagnosis, management and follow-up of coeliac patients and dermatitis herpetiformis in children and adults, both in primary care and in specialist settings. We developed four sections on diagnosis, gluten-free diet, follow-up and risk of complications in adults, one section focused on diagnosis and follow-up in children and one on the diagnosis and management of dermatitis herpetiformis. CONCLUSIONS These guidelines may support clinicians to improve the diagnosis and management of patients with coeliac disease.