Assessment of salivary microbiota profile as a potential diagnostic tool for pediatric celiac disease.

The association between oral dysbiosis and celiac disease (CD) remains poorly understood, as does the impact of CD-associated dysbiosis on disease development or exacerbation. This study aims to investigate alterations in salivary microbial composition among children with CD. In this cross-sectional study, saliva samples from 12 children with active CD (A-CD group), 14 children with CD on a gluten-free diet (GFD), and 10 healthy control (HC) children were analyzed using DNA sequencing targeting the 16S ribosomal RNA. Both patients in A-CD and GFD groups showed a significant increase (p = 0.0001) in the Bacteroidetes phylum, while the Actinobacteria phylum showed a significant decrease (p = 0.0001). Notably, the Rothia genus and R.aeria also demonstrated a significant decrease (p = 0.0001) within the both CD groups as compare to HC. Additionally, the control group displayed a significant increase (p = 0.006) in R.mucilaginosa species compared to both CD patient groups. Distinct bacterial strains were abundant in the saliva of patients with active CD, indicating a unique composition of the salivary microbiome in individuals with CD. These findings suggest that our approach to assessing salivary microbiota changes may contribute to developing noninvasive methods for diagnosing and treating CD.

[Gastrointestinal bleeding as debut of complicated celiac disease]. / Hemorragia digestiva como debut de enfermedad celiaca complicada.

Celiac disease (CD) is an autoimmune malabsorption syndrome that presents with intolerance to gluten (gliadin), a protein found in wheat. The most common symptoms are diarrhea, steatorrhea, weight loss, weakness, vitamin and mineral deficiency. The probability of developing complicated CD is relatively low, among its main manifestations we have refractory sprue, T-cell lymphoma and ulcerative jejunitis (UY) of which a few cases develop gastrointestinal bleeding. Furthermore, we present the case of a 51-year-old patient who developed intestinal hemorrhage due to complicated CD, where upper digestive video endoscopy (VEDA), video colonoscopy (VCC), capsule endoscopy (CE) and biopsy of the jejunum and ileum were performed confirming the diagnosis of CD along with ulcerative jejunoileitis.

Gluten Ataxia and mGluR1 Autoimmune Encephalitis Presenting as Acute Cerebellar Ataxia: A Case Report.

A Caucasian male in his 60s presented with acute onset of dizziness, dysarthria, and gait ataxia. Upon extensive workup, positive findings were cerebrospinal fluid (CSF) showing lymphocytic pleocytosis with oligoclonal bands, positive celiac disease autoantibodies in blood, a duodenal biopsy indicating lymphocytic infiltration, and positive anti-mGluR1 antibody titers in CSF. The patient was started on a strict gluten-free diet and intravenous immunoglobulin therapy for 5 days and showed mild consecutive improvements each day of treatment. He was discharged after 22 days, and was encouraged to continue gluten adherence, physical and speech therapy, and follow up with neuroimmunology. This report demonstrates that autoimmune encephalitis due to anti-mGluR1antibodies and gluten ataxia are both immune-mediated disorders that should be considered in acute cerebellar ataxia cases. By broadening the differential diagnosis and a comprehensive CSF analysis, identification of gluten ataxia and autoimmune encephalitis were beneficial in the management of this particular patient.

Coeliac Disease and Microscopic Colitis: The Largest Study Assessing Prognosis and Risk of Hospital Admission.

Microscopic colitis (MC) and coeliac disease (CD) are common associated gastrointestinal conditions. We present the largest study assessing hospitalisation in patients with MC and the effect of a concomitant diagnosis of CD. Data were retrospectively collected between January 2007 and December 2021 from all patients diagnosed with MC and compared to a database of patients with only CD. In total, 892 patients with MC (65% female, median age 65 years (IQR: 54-74 years) were identified, with 6.4% admitted to hospital due to a flare of MC. Patients admitted were older (76 vs. 65 years, p < 0.001) and presented with diarrhoea (87.7%), abdominal pain (26.3%), and acute kidney injury (17.5%). Treatment was given in 75.9% of patients, including intravenous fluids (39.5%), steroids (20.9%), and loperamide (16.3%). Concomitant CD was diagnosed in 3.3% of patients and diagnosed before MC (57 versus 64 years, p < 0.001). Patients with both conditions were diagnosed with CD later than patients with only CD (57 years versus 44 years, p < 0.001). In conclusion, older patients are at a higher risk of hospitalisation due to MC, and this is seen in patients with a concomitant diagnosis of CD too. Patients with MC are diagnosed with CD later than those without.

Rapid diagnosis of celiac disease based on plasma Raman spectroscopy combined with deep learning.

Celiac Disease (CD) is a primary malabsorption syndrome resulting from the interplay of genetic, immune, and dietary factors. CD negatively impacts daily activities and may lead to conditions such as osteoporosis, malignancies in the small intestine, ulcerative jejunitis, and enteritis, ultimately causing severe malnutrition. Therefore, an effective and rapid differentiation between healthy individuals and those with celiac disease is crucial for early diagnosis and treatment. This study utilizes Raman spectroscopy combined with deep learning models to achieve a non-invasive, rapid, and accurate diagnostic method for celiac disease and healthy controls. A total of 59 plasma samples, comprising 29 celiac disease cases and 30 healthy controls, were collected for experimental purposes. Convolutional Neural Network (CNN), Multi-Scale Convolutional Neural Network (MCNN), Residual Network (ResNet), and Deep Residual Shrinkage Network (DRSN) classification models were employed. The accuracy rates for these models were found to be 86.67%, 90.76%, 86.67% and 95.00%, respectively. Comparative validation results revealed that the DRSN model exhibited the best performance, with an AUC value and accuracy of 97.60% and 95%, respectively. This confirms the superiority of Raman spectroscopy combined with deep learning in the diagnosis of celiac disease.

Microscopic Colitis and Celiac Disease: Sharing More than a Diagnostic Overlap.

Microscopic colitis (MC) is an emergent group of chronic inflammatory diseases of the colon, and celiac disease (CD) is a chronic gluten-induced immune-mediated enteropathy affecting the small bowel. We performed a narrative review to provide an overview regarding the relationship between both disorders, analyzing the most recent studies published at the epidemiological, clinical and pathophysiological levels. In fact, MC and CD are concomitantly prevalent in approximately 6% of the cases, mainly in the subset of refractory patients. Thus, physicians should screen refractory patients with CD against MC and vice versa. Both disorders share more than a simple epidemiological association, being multifactorial diseases involving innate and adaptive immune responses to known or unknown luminal factors based on a rather common genetic ground. Moreover, autoimmunity is a shared characteristic between the patients with MC and those with CD, with autoimmunity in the latter being quite well-established. Furthermore, CD and MC share some common clinical symptoms and risk factors and overlap with other gastrointestinal diseases, but some differences exist between both disorders. More studies are therefore needed to better understand the complex mechanisms involving the common pathogenetic ground contributing to the CD and MC epidemiological association.

γδ+ T-Cells Is a Useful Biomarker for the Differential Diagnosis between Celiac Disease and Non-Celiac Gluten Sensitivity in Patients under Gluten Free Diet.

BACKGROUND: The differential diagnosis between patients with celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is difficult when a gluten-free diet (GFD) has been initiated before the diagnostic work-up. Isolated increases in TCRγδ+ and celiac lymphogram (increased TCRγδ+ plus decreased CD3-) may enable differential diagnosis in this challenging clinical setting. This study evaluated: (1) the accuracy of %TCRγδ+ and celiac lymphogram for diagnosing CD before and after GFD and for differentiation with NCGS; (2) TCRγδ+ kinetics at baseline and after starting GFD in both CD and NCGS. METHODS: The inclusion criteria were patients with CD (n = 104), NCGS (n = 37), and healthy volunteers (n = 18). An intestinal biopsy for intraepithelial lymphogram by flow cytometry was performed at baseline and after GFD. The optimal cutoff for CD diagnostic accuracy was established by maximizing the Youden index and via logistic regression. RESULTS: %TCRγδ+ showed better diagnostic accuracy than celiac lymphogram for identifying CD before and after GFD initiation. With a cutoff > 13.31, the accuracy for diagnosing CD in patients under GFD was 0.88 [0.80-0.93], whereas the accuracy for diagnosing NCGS (%TCRγδ+ ≤ 13.31) was 0.84 [0.76-0.89]. The percentage of TCRγδ+ cells showed differential kinetics between CD (baseline 22.7% [IQR, 16.4-33.6] vs. after GFD 26.4% [IQR, 17.8-36.8]; p = 0.026) and NCGS (baseline 9.4% [IQR, 4.1-14.6] vs. after GFD 6.4% [IQR, 3.2-11]; p = 0.022). CONCLUSION: TCRγδ+ T cell assessment accurately diagnoses CD before and after a GFD. Increased TCRγδ+ was maintained in the long term after GFD in CD but not in NCGS. Altogether, this suggests the potential usefulness of this marker for the differential diagnosis of these two entities in patients on a GFD.

SKELETAL HEALTH ASSESSMENT IN BRAZILIAN MEN WITH CELIAC DISEASE AT DIAGNOSIS: HOW IMPORTANT IS IT?

BACKGROUND: Low bone mass density (BMD) is an extraintestinal finding in celiac disease (CD). This may result in bone fractures leading to loss in quality of life. OBJECTIVE: To assess BMD in male CD patients at diagnosis according to the patient's age. METHODS: Descriptive retrospective carried out during the period between 2013 and 2023 in a single office that studied dual-energy X-ray absorptiometry (DXA) results in 28 male patients with a recent diagnosis of CD, divided into three groups: group 1 (age up to 18 years); group 2 (from 19 to 49 years of age) and group 3 (over 50 years of age). Were studied demographic and anthropometric parameters, time delay between symptoms onset and CD diagnosis and fracture occurrence. RESULTS: Celiac patients studied had median age 36.0 years (IQR=16.5-50.7). Among them, 39.3% had osteopenia and 14.3% had osteoporosis. Only 36% of the sample had normal DXA values (group 1 with 37.5%; group 2 with 46% and group 3 with 14.2%). No pathological fracture was observed in this sample. CD diagnosis delay observed had median 1.0 year (IQR=1.0-4.7). When the number of individuals with normal and abnormal DXA results were compared, there was no difference in body mass index, time of diagnosis delay or Marsh classification (P=0.18). CONCLUSION: Male patients at the time of CD diagnosis showed a high prevalence of low BMD, which was particularly evident in individuals over 50 years of age.

Diagnosis and Management of Celiac Disease.

This JAMA Clinical Guidelines Synopsis summarizes the American College of Gastroenterology's 2023 guideline update on diagnosis and management of celiac disease.

Celiac disease prevalence in patients with idiopathic inflammatory myopathies, a cross-sectional study.

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.

The Usefulness of Intraepithelial Lymphocyte Immunophenotype Testing for the Diagnosis of Coeliac Disease in Clinical Practice.

BACKGROUND: The diagnosis of coeliac disease (CD) in adults is based on clinical, serological and histological criteria. The inappropriate performance of intestinal biopsies, non-specificity of mild histological lesions and initiation of a gluten-free diet (GFD) before biopsy may hamper the diagnosis. In these situations, determining the intraepithelial lymphogram of the duodenum by flow cytometry (IEL-FC) can be helpful. OBJECTIVES: To describe the clinical scenarios in which the IEL-FC is used and its impact on the diagnosis of CD. METHODS: All adult patients with suspected CD at three tertiary centres for whom the duodenal histology and IEL-FC were available were identified. Catassi and Fasano's diagnostic criteria and changes to a CD diagnosis after the IEL-FCs were collected. RESULTS: A total of 348 patients were included. The following indications for an IEL-FC formed part of the initial study for CD (38%): negative conventional work-up (32%), already on a GFD before duodenal biopsies (29%) and refractoriness to a GFD (2%). The IEL-FC facilitated a definitive diagnosis in 93% of patients with an uncertain diagnosis who had had a conventional work-up for CD or who were on a GFD before histology. CONCLUSIONS: The IEL-FC facilitates the confirmation or rejection of a diagnosis of CD in clinical scenarios in which a conventional work-up may be insufficient.

Impact of Cigarette Smoking on Clinical Presentation and Treatment Response in Coeliac Disease.

BACKGROUND AND AIMS: The environmental factors, apart from gluten ingestion predisposing to coeliac disease are poorly known. Smoking is associated with many immune-mediated diseases, but research on coeliac disease is scarce. This study aims to investigate how smoking affects the clinical presentation, presence of comorbidities and response to gluten-free diet in coeliac disease. METHODS: Altogether 815 adults with coeliac disease participated in a nationwide cross-sectional study. Participants were interviewed and smoking habits (never, former, or current smoker), clinical presentation of coeliac disease and presence of comorbidities were elicited. Serology and severity of small bowel mucosal lesions at diagnosis were gathered from the participants' medical records and follow-up serology was measured. Gastrointestinal symptoms and psychological well-being were assessed using validated questionnaires. RESULTS: Current smokers were more often male and were diagnosed at younger ages than never or former smokers. There were no differences between the groups in clinical presentation, severity of symptoms or mucosal lesions at diagnosis or in dietary compliance and clinical, serological, and histological recovery. Musculoskeletal disorders, particularly osteoporosis and osteopenia, were more common in never smokers than in other groups (14.5% vs. 5.1% and 4.1%, p<0.001), and cardiovascular disorders were diagnosed more often in former smokers (36.2% vs. 23.5% and 21.9%, p=0.003). CONCLUSIONS: Smoking does not seem to have an impact on the clinical presentation, severity of symptoms or mucosal damage in coeliac disease. Histological and clinical recovery as well as seroconversion on gluten-free diet are not affected by smoking status.

IgE to wheat, prick test, and Patch test among children with celiac disease.

INTRODUCTION AND AIM: Celiac disease is one of the most common autoimmune disorders. This study aimed to evaluate the relationship between celiac disease and wheat sensitization. SUBJECTS AND METHODS: In the current study, children aged < 18 years with confirmed celiac disease were included. Data were analyzed using SPSS. RESULTS: Gastrointestinal problems were the most common indication for evaluation in terms of celiac disease. Prick and patch tests were positive in 43.4% and 34% respectively. CONCLUSION: Prick test and patch test for wheat sensitization were positive in about 30-45% of the children for celiac disease.

Chronic diarrhoea, weight loss and a positive anti-tissue transglutaminase antibody: A case report of olmesartan-induced enteropathy.

Olmesartan is an angiotensin II receptor blocker licensed for the treatment of hypertension. It can cause a sprue-like enteropathy (SLE), characterised by chronic diarrhoea, weight loss and villous atrophy. Transiently raised anti-tissue transglutaminase (ATTG) antibody has also been rarely reported in the literature.We describe the case of a woman in her mid-50s, who presented with a history of intermittent loose stools over 1 year, associated with significant weight loss. She had two marginally raised serum ATTG antibody tests during her work-up.After extensive investigations, she was diagnosed with olmesartan-induced enteropathy. On subsequent follow-up, her symptoms had resolved with cessation of her olmesartan therapy.This case adds to existing literature, highlighting the importance of considering olmesartan as a possible differential diagnosis for SLE. It also reports the presence of a raised ATTG antibody which is infrequently reported in this context.

Helicobacter pylori infection found during upper endoscopy performed for the diagnosis of celiac, inflammatory bowel diseases, and eosinophilic esophagitis: A multicenter pediatric European study.

BACKGROUND: Helicobacter pylori may be found during upper gastrointestinal endoscopy (UGE) performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD), and eosinophilic esophagitis (EoE). We aimed to describe the frequency of H. pylori in children undergoing UGE for CeD, IBD, and EoE and the number of children receiving eradication treatment. MATERIALS AND METHODS: A retrospective multicenter study from 14 countries included pediatric patients diagnosed with CeD, IBD, and EoE between January 2019 and December 2021. DATA COLLECTED: age, gender, hematologic parameters, endoscopic, histologic, and H. pylori culture results, and information on eradication treatment. RESULTS: H. pylori was identified in 349/3890 (9%) children [167 (48%) male, median 12 years (interquartile range 8.1-14.6)]. H. pylori was present in 10% (173/1733) CeD, 8.5% (110/1292) IBD and 7.6% (66/865) EoE patients (p = NS). The prevalence differed significantly between Europe (Eastern 5.2% (28/536), Southern 3.8% (78/2032), Western 5.6% (28/513)) and the Middle East 26.6% (215/809) [odds ratio (OR) 7.96 95% confidence interval (CI) (6.31-10.1) p < 0.0001]. Eradication treatment was prescribed in 131/349 (37.5%) patients, 34.6% CeD, 35.8% IBD, and 56.1% EoE. Predictors for recommending treatment included erosions/ulcers [OR 6.45 95% CI 3.62-11.47, p < 0.0001] and nodular gastritis [OR 2.25 95% CI 1.33-3.81, p 0.003]. Treatment rates were higher in centers with a low H. pylori prevalence (<20%) [OR 3.36 95% CI 1.47-7.66 p 0.004]. CONCLUSIONS: Identifying H. pylori incidentally during UGE performed for the most common gastrointestinal diseases varies significantly among regions but not among diseases. The indications for recommending treatment are not well defined, and less than 40% of children received treatment.

Outcome in pediatric celiac disease is independent of the diagnostic approach in patients with high antibody levels.

OBJECTIVES: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines enable the diagnosis of celiac disease (CD) without biopsies in patients with immunoglobulin A (IgA)-antibodies against tissue transglutaminase (TGA-IgA) ≥ 10× the upper limit of normal (ULN) and positivity of endomysial antibodies in a second blood sample. Limited data exist comparing the biopsy versus the nonbiopsy diagnostic approach regarding long-term outcomes in CD patients. Our study aimed to investigate the influence of the diagnostic approach on adherence to gluten-free diet (GFD), serological remission (defined as normalization of TGA-IgA during follow-up (FU)) and clinical remission in CD patients with TGA-IgA ≥ 10× ULN. METHODS: Retrospective multicenter study. Patients with CD and TGA-IgA ≥ 10× ULN at diagnosis were included in the study. Patients with confirmed diagnosis by biopsy were compared to patients diagnosed by nonbiopsy approach using univariate analysis, Kaplan-Meier survival curve, and logistic regression models. RESULTS: A total of 282 CD patients (192 [68.1%] in the biopsy group; 90 [31.9%] in the nonbiopsy group) were analyzed. The median time to normalization of TGA-IgA was 16.5 months [interquartile range, IQR: 13, 28] in the biopsy and 15 months [IQR: 12, 26] in the nonbiopsy group; p = 0.14). Rates of normalized TGA-IgA at first to third-year FU were comparable between both groups. Adherence to GFD did not seem to be influenced by the diagnostic approach. CONCLUSIONS: The nonbiopsy approach is not inferior to the biopsy approach in terms of adherence to GFD and serological remission in patients with CD.

Celiac disease - a pluripathological model in pediatric practice.

Being defined as an autoimmune, chronic pathology, frequently encountered in any age group, but especially in pediatrics, celiac disease (also called gluten enteropathy), is gaining more and more ground in terms of diagnosis, but also interest in research. The data from the literature of the last decades attest the chameleonic way of its presentation, there may be both classic onset symptoms and atypical symptoms. Given the impact played by celiac disease, especially in the optimal growth and development of children, the current narrative review aims to highlight the atypical presentation methods, intended to guide the clinician towards the inclusion of the pathology in the differential diagnosis scheme. To these we add the summary presentation of the general data and therapeutic lines regarding the underlying condition and the existing comorbidities. In order to place the related information up to date, we performed a literature review of the recent articles published in international databases. We bring forward the current theories and approaches regarding both classic celiac disease and its atypical manifestations. Among these we note mainly constitutional, skin or mucous, bone, neuro-psychic, renal, reproductive injuries, but also disorders of biological constants and association with multiple autoimmunities. Knowing and correlating them with celiac disease is the key to optimal management of patients, thus reducing the subsequent burden of the disease.

Nutrition Assessment and Management in Celiac Disease.

Celiac disease (CeD) is the most common immune condition affecting the gastrointestinal tract; it is triggered by gluten and the only available treatment is a strict gluten-free diet (GFD). Therefore, for patients with CeD, adopting a GFD is not a lifestyle choice. The major problem is that a GFD is restrictive and, like all restrictive diets, it has the potential for adverse nutritional outcomes, especially if adopted for a long term. It is well known that GFD can be nutritionally inadequate and is frequently associated with vitamin and mineral deficiencies; it is also associated with excessive sugar and fat intake, particularly when gluten-free substitutes are consumed. Consequently, people with CeD are affected by higher rates of overweight and obesity and metabolic complications, such as fatty liver and cardiovascular disease. Therefore, assessment of nutritional status and diet quality at diagnosis and while on a long-term GFD is key in the management of CeD. This narrative review addresses nutritional considerations in CeD and management of common challenges associated with a GFD.

Clinical Presentation and Spectrum of Gluten Symptomatology in Celiac Disease.

Views on the clinical presentation and symptomatology of celiac disease have evolved alongside advances in disease detection and understanding of disease pathogenesis. Although historically regarded as a pediatric illness characterized by malabsorption, it is now better viewed as an immune illness of gluten-specific T cells with systemic manifestations affecting all ages. Its broad presentation, including frequent extraintestinal manifestations and asymptomatic disease, contributes to suboptimal disease detection. Adverse symptoms greatly impact patient quality of life and can result from chronic gluten exposure in untreated disease or those poorly responsive to the gluten-free diet. They can also present as acute symptoms after episodic gluten exposure. Functional gastrointestinal disease is a common comorbidity. Biomarkers like interleukin-2 that are highly sensitive and specific for celiac disease highlight a role for gluten-specific T cells in acute gluten symptomatology. A mechanistic understanding of symptoms will inform approaches to better measure and treat them effectively.