Treatment Of Celiac Disease Research Articles

A Shared Path: Co-occurrence and Clinical Implications of Celiac Disease and Type 1 Diabetes Mellitus

Introduction: Celiac disease (CeD) and Type 1 diabetes mellitus (T1DM) are autoimmune diseases that sometimes co-occur in genetically predisposed people. Both diseases share common genetic factors, such as human leukocyte antigens: HLA-DQ2 and HLA-DQ8. Apart from that, they share environmental factors such as gluten exposure, viral infections, and alterations in gut microbiota composition. CeD is a gluten-induced disease resulting in inflammation and impaired absorption of the nutrients, leading to malnutrition. In T1DM, β-cells in the pancreatic tissue are destroyed during the T-cell mediated reaction, which leads to impaired insulin production and development of insulin deficiency which leads to hyperglycemia and chronic complications. Materials and methods: This study is based on a review of multiple articles and prospective studies we managed to find online in the PubMed database.Aim of the study: The aim of the study is to investigate the clinical implications of T1DM and CeD, focusing on the importance of early screening for CeD in patients with T1DM and evaluate the challenges in the management of both diseases simultaneously. Additionally, the study highlights the potential benefits of a personalized approach to treatment. Conclusions: The co-occurrence of CeD and T1DM is common and it’s determined by shared genetic, immune, and environmental factors. Early screening and diagnosis are very important regarding the management strategies for these conditions. Gluten free diet (GFD) is the main treatment for CeD, but its adherence may be challenging, especially in T1DM patients who already face many restrictions on a daily basis. Personalized treatment approaches seem to be essential for simultaneously managing and optimizing CeD and T1DM. However, the lower compliance to GFD among T1DM patients suggests the need for further research to provide support for long-term management of both T1DM and CeD.

Interpreting positive celiac serology in children with new-onset type 1 diabetes.

The association of celiac disease (CD) in type 1 diabetes mellitus (T1DM) is well-established, yet variation exists in screening practices. This study measures the accuracy of early screening with tissue transglutaminase Immunoglobulin A (TTG-IgA) and endomysial antibody (EMA) in newly diagnosed T1DM. This is a retrospective study of children with T1DM between 2013 and 2019 with early CD screening and follow-up. Data elements included anthropometrics, serologies, blood pH, bicarbonate, and Hemoglobin A1c. Celiac serologies were analyzed using chi-square and receiver operating characteristic curves to calculate optimal levels for predicting CD. A total of 1,292 children met inclusion criteria with 142 having positive celiac serologies; 47 (33.1 %) of whom were subsequently diagnosed with CD- an incidence of 3.6 %. All subjects with positive EMA and TTG-IgA≥8 times upper limit of normal were diagnosed with CD. Gastrointestinal symptoms, BMI, and thyroid disease were not statistically significant variables in this cohort, although there was a trend toward CD in lower BMI patients and higher TTG IgA in those with markedly elevated HgbA1c. Early celiac screening in T1DM is reliable and promotes timely CD diagnosis and treatment. Although transient positive celiac serologies were noted, the degree of TTG-IgA elevation and EMA positivity are strong predictors of coexisting CD. Larger prospective studies using these assays will further define the risk stratification algorithm that is needed for our T1DM community.

Postbiotics: As a Promising Tools in the Treatment of Celiac Disease.

Celiac disease (CD) can be considered an autoimmune problem, a disease caused by gluten sensitivity in the body. Gluten is found in foods such as barley, wheat, and rye. This ailment manifests in individuals with hereditary susceptibility and under the sway of environmental stimulants, counting, in addition to gluten and intestinal microbiota dysbiosis. Currently, the only recommended treatment for this condition is to follow a gluten-free diet for life. In this review, we scrutinized the studies of recent years that focused on the use of postbiotics in vitro and in vivo in CD. The investigation of postbiotics in CD could be intriguing to observe their diverse effects on several pathways. This study highlights the definitions, characteristics, and safety issues of postbiotics and their possible biological role in the prevention and treatment of CD, as well as their application in the food and drug industry.

Dietary assessments in individuals living with coeliac disease: key considerations.

Coeliac disease (CeD) is a type of enteropathy characterised by an immune-mediated reaction to ingested gluten, resulting in impaired absorption of nutrients and symptoms such as bloating, abdominal cramping and diarrhoea. Currently, the only treatment for CeD is adherence to a gluten-free diet (GFD). The latest draft guidance from the US Food and Drug Administration recommends that dietitians experienced in CeD management evaluate patients during the screening and treatment period of CeD clinical trials to assess adherence to a GFD. However, there are currently no standardised guidelines on dietary assessment of patients with CeD on a GFD and there is a lack of widespread availability of expertise in this field. Based on the findings of a literature review conducted between April and September 2023, this article provides an overview of key points to consider in the nutritional and dietary assessment of patients with CeD who are following a GFD, with particular focus on the clinical trial setting. Based on a consensus from dietitians and gastroenterologists experienced in treating patients with CeD, we present specific recommendations for registered dietitians who manage patients with CeD. We also describe the development of a simplified tool for assessment of adherence to a GFD, the Gluten-Free Adherence Survey, based on these recommendations. These guidelines cover nutritional and dietary assessment of patients with CeD, physical assessments, intake of oats, environmental considerations and the disease burden.

Coeliac Disease in Children—A Clinical Review Including Novel Treatment Agents

Coeliac disease (CD) affects almost of 1% of the population, yet remains undiagnosed in the majority. Though the demonstration of enteropathy in duodenal biopsy was traditionally the essential criterion for the diagnosis of coeliac disease, the guidelines published by the European Society of Paediatric Gastroenterology and Nutrition (ESPGHAN) in 2012, and revised in 2020, paved the way to a no-biopsy approach to diagnosis. In a select group of children meeting certain criteria, a definitive diagnosis of CD can now be made without the need for duodenal biopsies. This is being increasingly applied in clinical practice. It is well established that untreated coeliac disease is associated with several chronic adverse health conditions. At present, a strict gluten-free diet remains the only effective treatment for CD. The advances in our understanding of the pathogenesis of CD have led to a search for alternative treatment agents. Several investigational agents are in various phases of clinical trials at present. In this review, we outline the clinical aspects of coeliac disease and summarise various investigational treatment agents.

Circulating MicroRNAs and Cytokines Associated with Celiac Disease.

The current research examines the molecular terrain of celiac disease (CD) through microRNA (miRNA) and cytokines as potential new diagnostic and therapeutic markers. Gluten-appropriate immune response is a key feature of an autoimmune clinical entity known as CD that leads to inflammation and degeneration of small intestine mucosa. However, the mechanisms responsible for this remain unclear. Quantitative reverse transcription polymerase chain reaction (RT-qPCR ) was carried out on serum samples obtained from patients with CD and control groups to unravel their pathogenesis. Assessing miR-155, miR-15b, interleukin (IL)-2, IL-7, IL-35and IL-37 levels in expression might be useful in diagnosing or treating the disorder. A significant dysregulation of these molecular players in patients with CD compared with healthy controls has been evidenced by results from this study. For instance, miR-155 was up-regulated, whereas miR-15b was significantly down-regulated in CD, illustrating their roles in immune responses and inflammation-mediated processes. Besides, there was an over-expression of IL-2 and an under-expression of IL-37 in patients with CD, indicating these biomolecules' role in immuno-dysregulation and inflammatory process underlying CD. In addition, a positive correlation between IL-2 and miRNA 155 expression levels was observed in patients with CD, suggesting that they could be involved together with other cytokines, showing the interplay between immune response pathways and inflammatory cascades during CD pathogenesis. These molecular signature discoveries might result in new and revolutionary diagnostic modalities and molecular-targeted therapies for CD pathogenesis. When used with the scientific understanding of miRNAs and cytokines associated with CD pathophysiology, it creates a basis for personalized medicine based on the individualized molecular profile of all patients. This will undoubtedly increase the efficacy of CD treatment strategies. In brief, more research on molecular pathways' workings should be done to harness their potential in CD diagnosis and treatment.

The primary nutritional approach in pediatric celiac disease: a mini-review

Background: Celiac disease (CD) is chronic small bowel inflammation with villous atrophy, consequently, an immune-mediated disorder triggered by ingesting Gluten in wheat, barley, and rye in genetically susceptible individuals. Aims: Summarize the fundamental principles for managing the diet of patients with CD. This Mini-Review using relevant articles in PubMed's online databases followed the medical keywords Celiac Disease, Gluten, gluten-free diet, nutritional approach, and diet adherence. The institution's Ethics Committee has waived the need to review the ethical aspects of this text. The cornerstone of the treatment is the lifelong adherence to a Gluten-Free Diet (GFD). This dietary regimen, which forms the basis of the patient's treatment, requires eliminating all food components containing Gluten and its derivatives from the diet. However, the treatment approach has changed from focusing on food avoidance to a wide-ranging evaluation of the various factors influencing the dietary choices in the patient's life. The Global Approach to the Follow-up of Celiac Disease is based on 1) control of symptomatology and dietary adherence; 2) improving emotional and social wellness in treating CD patients, with the active involvement of a psychologist; and 3) ensuring successful education of both the child and the family about its management. Indeed, the impact of CD extends beyond the patient and affects the well-being of caregivers and 4) evaluate socioeconomic burden, considering that Gluten-free food products remain significantly more expensive than gluten-containing equivalents with variable availability. So, the GFD is the primary treatment for CD, and difficulties in managing the Disease can lead to impaired Quality of Life. In conclusion, strict adherence to the GFD is imperative, requiring a multidisciplinary team involving physicians, dietitians, and psychologists on a regular visit schedule to assess dietary adherence and avoid long-term complications.

In Vitro Protective Effect of Pea-Derived Peptides (PPs) via the Keap1/Nrf2 Signaling Pathway on Alpha-Gliadin-Sensitizing Peptide Induced Cacao-2 Cells.

Celiac disease (CD) is an allergic intestinal disease caused mainly by gliadin in wheat, which is widespread in the population and currently lacks effective treatment. α-Gliadin peptides cause cellular damage by substantially increasing cellular reactive oxygen species (ROS) levels. This study investigates the protective effect of 11 pea-derived peptides (PPs) on ɑ-gliadin peptide (P31-43) treated Caco-2 cells. Results show that cells treated with PP2, PP5, and PP6 peptides significantly reduce the cell mortality caused by P31-43. Three PPs significantly reduce the P31-43-induced decrease in ROS levels to control levels, and there is no difference between them and the vitamin C (Vc) group. The results in terms of antioxidant-related enzymes show that PPs significantly decrease superoxide dismutase activity (SOD), glutathione reductases (GR), and glutathione (GSH)/oxidized glutathione (GSSG) levels, thus significantly enhancing the antioxidant level of cells. By studying the key proteins of the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2) pathway, it is found that PPs activate the Keap1/Nrf2 signaling pathway. The study finds that peptides from peas can effectively alleviate ɑ-gliadin peptide-induced cell damage. The discovery of these food-derived peptides provides novel potential solutions for the prevention and treatment of CD.

Celiac Disease, Gluten-Free Diet and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Celiac disease (CD) is a chronic autoimmune disorder triggered by the ingestion of gluten-containing food by genetically predisposed individuals. Hence, treatment of CD consists of permanent avoidance of wheat, rye, barley, and other gluten-containing foods. Lifelong adherence to a gluten-free diet (GFD) improves the symptoms of CD, but recent evidence suggests it is also associated with a higher risk for hepatic steatosis and the coexistence or emergence of other cardiometabolic risk factors. Moreover, a higher risk for liver steatosis is also reported by some authors as a potential extraintestinal complication of the CD itself. Recent nomenclature changes designate the association between hepatic steatosis and at least one of five cardiometabolic risk factors as metabolic dysfunction-associated steatotic liver disease (MASLD). An extended network of potentially causative factors underlying the association between MAFLD and CD, before and after dietary therapy is implemented, was recently described. The individualized treatment of these patients is less supported by evidence, with most of the current recommendations relying on empiric clinical judgment. This review focuses on the causative associations between CD and hepatic injury, either as an extraintestinal manifestation of CD or a side effect of GFD, also referring to potential therapeutic strategies for these individuals.

Assessment of dietary patterns in celiac disease patients using factor analysis method and their relationship with dietary intakes and body mass index

Background/ObjectivesCeliac disease (CD) is a systemic and autoimmune enteropathy of the gastrointestinal tract with malabsorption characteristics. The only effective treatment for CD is adhere strictly to a gluten-free diet (GFD) throughout life. We evaluated the dietary patterns in celiac disease patients and their association with dietary intakes and anthropometric measurements in Iran.Subjects/MethodsThis is a case-control study on 182 participants who were referred to the Khuzestan Celiac Association, Iran. Nutritional information was collected using a validated 147-item semi-quantitative food frequency questionnaire (FFQ). The software Stata (StataCorp, Version 14.0) was used to analyze the data. Principal component analysis (PCA) was used to obtain participants’ dietary patterns.ResultsA significant relationship was observed between age and body mass index (BMI) across quartiles of the healthy dietary pattern score (P < 0.001, P = 0.001, and P = 0.001, respectively), indicating that as age and BMI increased, participants demonstrated greater adherence to the healthy dietary pattern. Individuals with the highest adherence to the healthy dietary pattern had the lowest odds ratio for celiac disease (CD) (Q1: reference; Q2: 1.96, 95% CI: 0.84–4.55; Q3: 0.61, 95% CI: 0.27–1.42; Q4: 0.10, 95% CI: 0.03–0.33, P trend < 0.001), and this association remained significant after adjusting for BMI (adjusted P trend = 0.003) and energy intake (adjusted P trend < 0.001). Moreover, there was a significant association between the lowest odds ratio for CD and the highest adherence to the unhealthy dietary pattern after adjustment for energy intake (Q1: reference; Q2: 0.38, 95% CI: 0.13–1.12; Q3: 0.21, 95% CI: 0.06–0.71; Q4: 0.07, 95% CI: 0.02–0.29, adjusted P trend < 0.001). Additionally, a significant association was observed between the odds ratio for CD and the mixed dietary pattern score (Q1: reference; Q2: 6.01, 95% CI: 2.29–15.72; Q3: 2.47, 95% CI: 0.93–6.55; Q4: 4.84, 95% CI: 1.84–12.66, P trend = 0.02), and this association remained significant after adjustment for energy intake (adjusted P trend < 0.001).ConclusionsThe findings of the present study indicate that individuals who adhere to healthy dietary patterns have a lower incidence of celiac disease.

Health-related quality of life among celiacs in Portugal: a comparison between general and specific questionnaires.

This study aimed to compare the 36-Item Short Form Survey Instrument version 2 (SF-36-v2) (generic) and Celiac Disease Questionnaire (CDQ) (specific) questionnaires used to evaluate the quality of life (QoL) in celiac Portuguese adult individuals. This cross-sectional study used non-probabilistic sampling based on Portuguese celiac patients who accessed the online survey in 2022. The online data collection used a self-reported instrument composed of three parts: (i) socioeconomic, health, and gluten-free diet (GFD) adherence questions; (ii) SF-36 v2 - Portuguese version (generic questionnaire) and (iii) Celiac Disease Questionnaire (CDQ) (specific questionnaire). A total of 234 individuals who accessed the survey completed the questionnaire. Seven of the eight SF-36 domains positively correlated to the specific questionnaire CDQ. The "General Health" domain (domain 4) showed a negative correlation with the CDQ. Differences in content between the two instruments might be able to explain this finding since the CDQ explores issues regarding the specificities of celiac disease (CD) and the lifelong GFD burden. About half of the sample from this study displayed poor diet adherence, it is possible that the SF-36 could not reflect the impact of CD treatment - the complete elimination of gluten from the diet - on patients' health. Therefore, this issue should be carefully evaluated in future research. Specific validated questionnaires for CD individuals, such as the CDQ, contemplate social, economic, and clinical variables that permeate the patient's life context. Therefore, these instruments may be more suitable for evaluating QoL in this public. However, using a general questionnaire such as the SF-36 would be indicated for comparing QOL between celiac patients and the general population or even between CD and other disease individuals. In this case, we recommend assessing GFD compliance for control parallelly.

Enfermedad celíaca

Enfermedad celíaca

Investigation of cost and availability of gluten-free food in Jeddah, KSA

The prevalence of celiac disease (CD) in KSA is progressively increasing. Consistent adherence to a gluten-free (GF) diet is the only effective CD treatment. The availability and cost of GF food are important factors in adherence to a GFD. The objective of this study was to investigate the cost and availability of GF food in a sample of local stores and supermarkets across Jeddah province in KSA. Eleven supermarkets in Jeddah, KSA, ranging from high budget/quality supermarkets to low-budget stores, were visited. Eight food categories were evaluated, including flour, breakfast cereals, breads, pastas, and snacks (e.g., biscuits, cookies, snack bars, and chips). The availability and cost of GF and gluten containing (GC) items within these food categories were recorded. Each item included in these food categories was counted, and the overall average price was calculated. A total of 233GF and 24GC products were found. Supermarket 1 had the highest availability of GF foods (n=90), followed by supermarket 2 (n=34), supermarket 3 (n=30), supermarket 4 (n=23), supermarket 5 (n=21), supermarket 6 (n=18), supermarket 7 (n=9), and supermarket 8 (n=8). The median price per 100g was significantly greater for GF than GC products (p<0.05). The cost of GF products was significantly higher than that of GC products (p<0.05); consequently, GF foods were twice as expensive as their GC counterparts. The availability of GF products was limited, and GF products were more expensive than standard GC products. High cost and limited availability are major roadblocks to GFD adherence among people with CD. Governmental organizations must cooperate with healthcare providers and food industries to ensure that GF foods are widely available and affordable for people with CD, to minimize financial pressure and improve health quality.

Gut microbiota in celiac disease.

Celiac disease (CD) is an autoimmune gastrointestinal disease triggered by dietary gluten, occurring in genetically predisposed individuals. Currently, a gluten-free diet is the only current evidenced-based treatment for CD. With the growing prevalence of this condition worldwide, adjuvant therapies are needed. We understand that there are several factors that influence the pathogenesis of the condition. There is a complex interplay between genetics, environmental triggers, the immune system and gut microbiota. Recently, there has been a growing focus on the significance of gut microbiota in several autoimmune-based conditions. In particular, there has been much research involving the role of microbial flora and CD. Here, in this mini-review, we highlight the importance of gut microbiota and the symbiotic relationship with the host, introduce key factors that influence the development of the intestinal flora in early colonization, and ultimately explore its role in the pathogenesis of CD.

Emerging Pharmaceutical Therapies to Address the Inadequacy of a Gluten-Free Diet for Celiac Disease.

Celiac disease (CeD) is a chronic autoimmune disorder triggered by the ingestion of gluten, affecting around 1% of the global population. It is a multifactorial disease involving both genetics and environmental factors. Nowadays, the only available treatment for CeD is a life-long gluten-free diet (GFD), which can cause a significant burden for patients, since symptoms and mucosal injury can persist despite apparent compliance with a GFD. This could also lead to psychological consequences and affect the quality of life of these patients. Thankfully, recent advances in understanding the pathogenesis of CeD and the availability of various targets have made it feasible to explore pharmaceutical treatments specific to CeD. Recently, the FDA has highlighted the unmet needs of adult patients on a GFD who experience ongoing symptoms attributed to CeD and also show persistent duodenal villous atrophy. This review will outline the limitations of a GFD, describe the targets of potential novel treatment of CeD and provide an overview of the primary clinical trials involving oral and injectable agents for a non-dietary treatment of CeD.

Guidelines for best practices in monitoring established coeliac disease in adult patients.

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.

Dynamics of Serologic Change to Gluten in Celiac Disease Patients.

Serologic measures of tissue transglutaminase (tTG) immunoglobulin A (IgA) and deamidated gliadin peptide (DGP) IgA and immunoglobulin G (IgG) are hallmark tests utilized when diagnosing individuals for celiac disease (CeD) and for monitoring adherence to a gluten-free diet (GFD), currently the only available treatment for CeD. We address two issues in this study: (i) the relapse to seropositivity for CeD patients who resume a gluten containing diet and (ii) the correlation between two different tTG-IgA assays near the upper limit of normal (ULN) designated thresholds. Regarding the first issue, often a suspected CeD individual is put back on a gluten diet to return to their serologic levels. However, we show it requires a substantial amount of gluten for serology to return to a positive level. For example, in one study of 22 patients treated with placebo and taking 84 g of gluten over 6 weeks, only two converted from seronegative to seropositive for tTG-IgA. Regarding the second topic, we compare the relationship for different serologic assays, namely tTG-IgA AB (recombinant, ULN = 4 units/mL) vs. tTG-IgA (non-recombinant, ULN = 20 units). There is a strong correlation between both measurements as evidenced by a Pearson coefficient of R = 0.8584; however, we observed that the cross-correlation in terms of sensitivity and specificity improved substantially by using an ULN value of three instead of four for the tTG-IgA AB (recombinant) assay. This result suggests that assay thresholds used for initial diagnosis in patients who have not yet started a GFD may need to be adjusted for monitoring and in the setting of a diagnostic gluten challenge.

Osteoporosis and bone fractures in patients with celiac disease: A nationwide cohort study.

Celiac disease (CD) is an autoimmune disease caused by an abnormal immune response triggered by ingestion of gluten. Treatment of CD is a lifelong gluten-free diet. Both diagnosed and undiagnosed CD has been found to be associated with reduced bone mineral density, which can lead to an increased risk of fractures. We therefore aimed to investigate the association of CD and the risk of fractures and osteoporosis in Denmark in a nationwide registry-based study. We identified all patients with CD (ICD-10 code K90.0) between 2000 and 2018 and included those with at least two contacts with a CD diagnosis. In total, 9397 CD patients and 93,964 randomly selected age- and sex-matched (1:10) references from the general population were identified. The overall hazard ratio (HR) of developing osteoporosis in CD patients compared with matches was 5.39 (95% confidence interval (CI): 4.89, 5.95), however when excluding events of osteoporosis occurring within 12months from the date of diagnosis the overall HR was reduced to 3.87 (95% CI: 3.44, 4.33). The HR for major osteoporotic fractures was 1.37 (95% CI: 1.25, 1.51) and for any fractures 1.27 (95% CI: 1.18, 1.36). For osteoporosis, major osteoporotic fractures, and any fracture prior to diagnosis of CD the odds ratios comparing CD patients with matches were 4.32 (95% CI: 3.64, 4.68), 1.29 (95% CI: 1.21, 1.37) and 1.34 (95% CI: 1.27, 1.41), respectively. Thus, this study showed an increased risk of osteoporosis and bone fractures among individuals with CD, both before and after diagnosis of CD. These results underline that the risk of osteoporosis should be considered in the clinical management of patients with CD and that early diagnosis and treatment could be important.

Cross-sectional imaging: current status and future potential in adult celiac disease.

Celiac disease (CD), triggered by exposure to gluten in genetically susceptible individuals, is an immune-mediated small bowel disease affecting about 1% of the population worldwide. But the prevalence of CD varies with age, sex, and location. A strict gluten-free diet remains the primary treatment for CD, currently. Most of patients with CD respond well to gluten-free diet with good prognosis, while some patients fail to get symptomatic relief or histological remission (e.g., nonresponsive or refractory CD). Because of heterogeneous clinical appearance, the diagnosis of CD is difficult. Moreover, malignant complications and poor outcomes accompanied with refractory CD present great challenges in disease management. Over the past three decades, cross-sectional imaging techniques (computed tomography [CT] and magnetic resonance imaging [MRI]) play an important role in small bowel inflammatory and neoplastic diseases. Compared with endoscopic techniques, cross-sectional imaging permits clearly presentation of both intraluminal and extraluminal abnormalities. It provides vascular and functional information, thus improving the possibility as diagnostic and follow-up tool. The value of cross-sectional imaging for patients with suspected or confirmed CD has been gradually demonstrated. Studies revealed that certain features suggested by cross-sectional imaging could help to establish the early diagnosis of CD. Besides, the potential contributions of cross-sectional imaging may lie in the evaluation of disease activity and severity, which helps guiding management strategies. The purpose of this review is to provide current overviews and future directions of cross-sectional imaging in adult CD, thus facilitating the understanding and application in clinical practice. CLINICAL RELEVANCE STATEMENT: In this review, we systematically summarized the existing knowledge of cross-sectional imaging in adult CD and analyzed their possible roles in clinical practice, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. KEY POINTS: • Regarding a condition described as "celiac iceberg", celiac disease remains underdiagnosed and undertreated. • Cross-sectional imaging is helpful in clinical management of celiac disease, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. • Cross-sectional imaging should be considered as the valuable examination in patients suspected from celiac disease.

Old and New Adjunctive Therapies in Celiac Disease and Refractory Celiac Disease: A Review.

Celiac disease (CD) is a chronic enteropathy caused by the ingestion of gluten in a genetically susceptible individual. Currently, a gluten-free diet (GFD) is the only recommended treatment. However, unintentional gluten ingestion or a persistent villous atrophy with malabsorption (regardless of a strict GFD) as in the case of Refractory Celiac Disease (RCD) represents a major issue. In this review, we have analysed and discussed data from both randomized controlled trials and observational studies concerning adjunctive therapies as well as novel therapies for the treatment of CD and RCD. The literature search was carried out through Medline and Scopus. In total, 2268 articles have been identified and 49 were included in this review (36 studies resulting from the search strategy and 13 from other sources). Today, GFD remains the only effective treatment, although steroids, mesalamine, and more recently biological therapies have found space in the complex management of RCD. Currently, studies evaluating the effectiveness of novel therapies are still limited and preliminary results have been controversial.