Recent PubMed Articles on Coeliac Disease (External)

Pediatric Celiac Disease in Central and East Asia: Current Knowledge and Prevalence.

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Pediatric Celiac Disease in Central and East Asia: Current Knowledge and Prevalence.

Medicina (Kaunas). 2019 Jan 12;55(1):

Authors: Poddighe D, Rakhimzhanova M, Marchenko Y, Catassi C

Abstract
The current prevalence of pediatric Celiac Disease (CD) is estimated to be around 1% in the general population, worldwide. However, according to the geographic area, a great variability of CD prevalence has been described. Whereas a number of studies are available from Europe, North and South America, Australia, South-West Asia, and North Africa, the knowledge and awareness of CD in large parts of the remaining world areas is definitively poor. In several countries of Central and East Asia, the consumption of wheat is consistent and/or has significantly increased in recent decades, and CD is supposed to be underdiagnosed in children. In this mini-review, we aimed to summarize the current knowledge about the prevalence of pediatric CD in Central and East Asia, paying attention to the HLA-DQ immunogenetic background as well. Indeed, CD is likely not to be as uncommon as previously or currently thought in countries like Russia, Kazakhstan, and China, in addition to India, where pediatric CD has been clearly showed to be quite prevalent. Therefore, there is an urgent need for population-based studies on the prevalence of CD in those countries, especially in children, in order to increase the awareness of this disease and to improve the diagnostic strategy in these areas.

PMID: 30642036 [PubMed - indexed for MEDLINE]

Daily Life Restrictions are Common and Associated with Health Concerns and Dietary Challenges in Adult Celiac Disease Patients Diagnosed in Childhood.

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Daily Life Restrictions are Common and Associated with Health Concerns and Dietary Challenges in Adult Celiac Disease Patients Diagnosed in Childhood.

Nutrients. 2019 Jul 25;11(8):

Authors: Leinonen H, Kivelä L, Lähdeaho ML, Huhtala H, Kaukinen K, Kurppa K

Abstract
The prevalence and associated factors of daily life restrictions due to a gluten-free diet in adult celiac disease patients diagnosed in childhood are poorly known. We investigated these issues by collecting the medical data of 955 pediatric patients and sending questionnaires evaluating various health outcomes to the 559 patients who had reached adulthood. Of the 231 respondents, 46% reported everyday life restrictions caused by dietary treatment. Compared with those without restrictions, they more often had anemia at diagnosis (37% vs. 22%, p = 0.014), but the groups were comparable in other diagnostic features. In adulthood, patients with restrictions reported more overall symptoms (32% vs. 17%, p = 0.006), although the symptoms measured with the Gastrointestinal Symptom Rating Scale questionnaire were comparable. Despite strict dietary adherence in both groups, the experience of restrictions was associated with dietary challenges (34% vs. 9%, p < 0.001), health concerns (22% vs. 13%, p = 0.050), and lower vitality scores in the Psychological General Well-Being questionnaire. The groups did not differ in their current age, socioeconomic status, family history of celiac disease, general health or health-related lifestyle, the presence of co-morbidities, or regular follow up. Our results encourage healthcare professionals to discuss the possible health concerns and dietary challenges with patients to avoid unnecessary daily life restrictions, especially when young patients start to take responsibility for their treatment.

PMID: 31349675 [PubMed - in process]

Gluten Intake in Early Childhood and Risk of Celiac Disease in Childhood: A Nationwide Cohort Study.

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Gluten Intake in Early Childhood and Risk of Celiac Disease in Childhood: A Nationwide Cohort Study.

Am J Gastroenterol. 2019 Jul 23;:

Authors: Lund-Blix NA, Mårild K, Tapia G, Norris JM, Stene LC, Størdal K

Abstract
OBJECTIVES: Celiac disease (CD) may occur in genetically predisposed individuals exposed to gluten, but it is unclear whether the amount of gluten influences the risk of disease. We aimed at determining whether the amount of gluten intake at age 18 months predicted later risk of CD.
METHODS: In an observational nationwide cohort study, the Norwegian Mother and Child Cohort Study (MoBa), we included 67,608 children born during 2000-2009 and followed up for a mean of 11.5 years (range 7.5-15.5) after exclusions for missing data. Information regarding CD diagnosis was obtained from the Norwegian Patient Register 2008-2016 and from parental questionnaires at child age 7 and 8 years. We estimated gluten intake at age 18 months from a prospectively collected parental questionnaire.
RESULTS: CD was diagnosed in 738 children (1.1%, 62% girls). The mean estimated amount of gluten in the diet at 18 months was 8.8 g/d (SD 3.6). The adjusted relative risk of CD was 1.10 (95% confidence interval 1.03-1.18) per SD increase in daily gluten amount at age 18 months. Children in the upper quartile of gluten intake compared with the lower quartile had an increased risk of CD (adjusted relative risk 1.29, 95% confidence interval 1.06-1.58). The association with gluten amount was independent of the age at introduction of gluten. Gluten introduction ≥6 months was also an independent risk factor for CD.
DISCUSSION: In this nationwide study, increased gluten intake at 18 months was associated with a modestly increased risk of CD later in childhood.

PMID: 31343439 [PubMed - as supplied by publisher]

Coexistence of Excessive Weight Gain and Celiac Disease in Children: An Unusual Familial Condition.

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Coexistence of Excessive Weight Gain and Celiac Disease in Children: An Unusual Familial Condition.

Pediatr Gastroenterol Hepatol Nutr. 2019 Jul;22(4):407-412

Authors: Calcaterra V, Regalbuto C, Madè A, Magistrali M, Leonard MM, Cena H

Abstract
Excessive weight gain in children diagnosed with celiac disease (CD) is becoming more common. We describe 2 siblings (9-year and 6 months-old female and 6-year and 9 months-old male) with obesity showing attenuated gastrointestinal and atypical symptoms in which CD was diagnosed in the absence of a known family history of CD. After children's diagnosis, CD in their parents was also investigated. It was detected in their father affected by overweight. The presentation of patients with CD has changed. While patients with overweight and obesity commonly have symptoms such as abdominal pain, reflux, headache, and constipation due to lifestyle factors, CD should also be considered in patients with or without a family history of CD. Careful nutritional status assessment and follow-up monitoring after the diagnosis of CD are mandatory, especially in subjects who are already overweight at the presentation of this disease.

PMID: 31338317 [PubMed]

Tissue Transglutaminase Antibody and Its Association with Duodenal Biopsy in Diagnosis of Pediatric Celiac Disease.

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Tissue Transglutaminase Antibody and Its Association with Duodenal Biopsy in Diagnosis of Pediatric Celiac Disease.

Pediatr Gastroenterol Hepatol Nutr. 2019 Jul;22(4):350-357

Authors: Meena DK, Akunuri S, Meena P, Bhramer A, Sharma SD, Gupta R

Abstract
Purpose: This study aimed to evaluate a possible association between the anti-tissue transglutaminase antibody (anti-tTG) titer and stage of duodenal mucosal damage and assess a possible cut-off value of anti-tTG at which celiac disease (CD) may be diagnosed in children in conjunction with clinical judgment.
Methods: This observational study was conducted at a gastroenterology clinic in a tertiary hospital from April 2012 to May 2013. Seventy children between 6-months and 18-years-old with suspected CD underwent celiac serology and duodenal biopsy. Statistical analyses were done using SPSS 16. Diagnostic test values were determined for comparing the anti-tTG titer with duodenal biopsy. An analysis of variance and Tukey-Kramer tests were performed for comparing the means between groups. A receiver operating characteristics curve was plotted to determine various cut-off values of anti-tTG.
Results: The mean antibody titer increased with severity of Marsh staging (p<0.001). An immunoglobulin (Ig) A-tTG value at 115 AU/mL had 76% sensitivity and 100% specificity with a 100% positive predictive value (PPV) and 17% negative predictive value (NPV) for diagnosis of CD (p<0.001, 95% confidence interval [CI], 0.75-1).
Conclusion: There is an association between the anti-tTG titer and stage of duodenal mucosal injury in children with CD. An anti-tTG value of 115 AU/mL (6.4 times the upper normal limit) had 76% sensitivity, 100% specificity, with a 100% PPV, and 17% NPV for diagnosing CD (95% CI, 0.75-1). This cut-off may be used in combination with clinical judgment to diagnose CD.

PMID: 31338310 [PubMed]

Nutritional Deficiencies in Children with Celiac Disease Resulting from a Gluten-Free Diet: A Systematic Review.

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Nutritional Deficiencies in Children with Celiac Disease Resulting from a Gluten-Free Diet: A Systematic Review.

Nutrients. 2019 Jul 13;11(7):

Authors: Nardo GD, Villa MP, Conti L, Ranucci G, Pacchiarotti C, Principessa L, Raucci U, Parisi P

Abstract
BACKGROUND: A strictly gluten-free diet (GFD) is the basis for managing celiac disease (CD). Numerous studies have reported nutritional deficiencies/imbalances ascribable to a GFD. The aim of this review is to describe nutritional deficiencies observed in children with celiac disease on a GFD, to discuss the clinical consequences related to these nutritional imbalances, and to identify strategies that may be adopted to treat them.
METHODS: We reviewed the MEDLINE and EMBASE databases between January 1998 and January 2019.
RESULTS: Children are, regardless of whether they are on a gluten-free diet or not, at risk of consuming too much fat and insufficient fiber, iron, vitamin D, and calcium. These imbalances may be exacerbated when children are on a gluten-free diet. In particular, the intake of folate, magnesium, zinc, and foods with a high glycemic index in children with CD who are on a GFD is significantly altered.
CONCLUSIONS: Therapeutic protocols should include nutritional education to help teach subjects affected by disorders such as CD the importance of labels, the choice of foods, and the combination of macro- and micronutrients. Children with CD on a GFD should be encouraged to rotate pseudo-cereals, consume gluten-free commercial products that have been fortified or enriched, and use foods that are local and naturally gluten-free.

PMID: 31337023 [PubMed - in process]

Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation.

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Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation.

BMC Pediatr. 2019 Jul 22;19(1):247

Authors: Iqbal NT, Syed S, Sadiq K, Khan MN, Iqbal J, Ma JZ, Umrani F, Ahmed S, Maier EA, Denson LA, Haberman Y, McNeal MM, Setchell KDR, Zhao X, Qureshi S, Shen L, Moskaluk CA, Liu TC, Yilmaz O, Brown DE, Barratt MJ, Kung VL, Gordon JI, Moore SR, Ali SA

Abstract
BACKGROUND: Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children < 5 years are attributable to under-nutrition, making the study of EE an area of critical priority.
METHODS: Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) < - 2) children, and well-nourished (WHZ > 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn's disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community.
DISCUSSION: Operational and ethical constraints for safely obtaining intestinal biopsies from children in resource-poor settings have led to a paucity of human tissue-based investigations to understand and reverse EE in vulnerable populations. Furthermore, EE biomarkers have rarely been correlated with gold standard histopathological confirmation. The Study of Environmental Enteropathy and Malnutrition (SEEM) is designed to better understand the pathophysiology, predictors, biomarkers, and potential management strategies of EE to inform strategies to eradicate this debilitating pathology and accelerate progress towards the 2030 Sustainable Development Goals.
TRIAL REGISTRATION: Retrospectively registered; clinicaltrials.gov ID NCT03588013 .

PMID: 31331393 [PubMed - in process]

Celiac disease: a comprehensive current review.

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Celiac disease: a comprehensive current review.

BMC Med. 2019 Jul 23;17(1):142

Authors: Caio G, Volta U, Sapone A, Leffler DA, De Giorgio R, Catassi C, Fasano A

Abstract
BACKGROUND: Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options.
MAIN BODY: A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic 'gold standard', highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma.
CONCLUSIONS: The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.

PMID: 31331324 [PubMed - in process]

HLA-DQA1 and HLA-DQB1 Alleles, Conferring Susceptibility to Celiac Disease and Type 1 Diabetes, are More Expressed Than Non-Predisposing Alleles and are Coordinately Regulated.

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HLA-DQA1 and HLA-DQB1 Alleles, Conferring Susceptibility to Celiac Disease and Type 1 Diabetes, are More Expressed Than Non-Predisposing Alleles and are Coordinately Regulated.

Cells. 2019 Jul 19;8(7):

Authors: Farina F, Picascia S, Pisapia L, Barba P, Vitale S, Franzese A, Mozzillo E, Gianfrani C, Del Pozzo G G

Abstract
HLA DQA1*05 and DQB1*02 alleles encoding the DQ2.5 molecule and HLA DQA1*03 and DQB1*03 alleles encoding DQ8 molecules are strongly associated with celiac disease (CD) and type 1 diabetes (T1D), two common autoimmune diseases (AD). We previously demonstrated that DQ2.5 genes showed a higher expression with respect to non-CD associated alleles in heterozygous DQ2.5 positive (HLA DR1/DR3) antigen presenting cells (APC) of CD patients. This differential expression affected the level of the encoded DQ2.5 molecules on the APC surface and established the strength of gluten-specific CD4+ T cells response. Here, we expanded the expression analysis of risk alleles in patients affected by T1D or by T1D and CD comorbidity. In agreement with previous findings, we found that DQ2.5 and DQ8 risk alleles are more expressed than non-associated alleles also in T1D patients and favor the self-antigen presentation. To investigate the mechanism causing the high expression of risk alleles, we focused on HLA DQA1*05 and DQB1*02 alleles and, by ectopic expression of a single mRNA, we modified the quantitative equilibrium among the two transcripts. After transfection of DR7/DR14 B-LCL with HLA-DQA1*05 cDNA, we observed an overexpression of the endogenous DQB1*02 allele. The DQ2.5 heterodimer synthesized was functional and able to present gluten antigens to cognate CD4+ T cells. Our results indicated that the high expression of alpha and beta transcripts, encoding for the DQ2.5 heterodimeric molecules, was strictly coordinated by a mechanism acting at a transcriptional level. These findings suggested that, in addition to the predisposing HLA-DQ genotype, also the expression of risk alleles contributed to the establishment of autoimmunity.

PMID: 31331105 [PubMed - in process]

Human intraepithelial lymphocytes.

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Human intraepithelial lymphocytes.

Mucosal Immunol. 2018 09;11(5):1281-1289

Authors: Mayassi T, Jabri B

Abstract
The location of intraepithelial lymphocytes (IEL) between epithelial cells, their effector memory, cytolytic and inflammatory phenotype positions them to kill infected epithelial cells and protect the intestine against pathogens. Human TCRαβ+CD8αβ+ IEL have the dual capacity to recognize modified self via natural killer (NK) receptors (autoreactivity) as well as foreign antigen via the T cell receptor (TCR), which is accomplished in mouse by two cell subsets, the naturally occurring TCRαβ+CD8αα+ and adaptively induced TCRαβ+CD8αβ+ IEL subsets, respectively. The private/oligoclonal nature of the TCR repertoire of both human and mouse IEL suggests local environmental factors dictate the specificity of IEL responses. The line between sensing of foreign antigens and autoreactivity is blurred for IEL in celiac disease, where recognition of stress ligands by induced activating NK receptors in conjunction with inflammatory signals such as IL-15 can result in low-affinity TCR/non-cognate antigen and NK receptor/stress ligand interactions triggering destruction of intestinal epithelial cells.

PMID: 29674648 [PubMed - indexed for MEDLINE]

Survey of the initial management of celiac disease antibody tests by ordering physicians.

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Survey of the initial management of celiac disease antibody tests by ordering physicians.

BMC Pediatr. 2019 Jul 19;19(1):243

Authors: Potter K, de Koning L, Butzner JD, Gidrewicz D

Abstract
BACKGROUND: Appropriate interpretation of a positive celiac antibody test by an ordering physician is important in order to institute proper management. We evaluated why children with an initial positive celiac serology were not referred for diagnostic biopsy or followed with serial testing by the ordering physician.
METHODS: Consecutive celiac serologies in all patients less than 18 years of age were evaluated over 3.5 years and 775 children with a positive tissue transglutaminase antibody (TTG) were identified. If no management of a positive TTG could be identified, a survey was sent to the ordering physician. Responses were categorized as appropriate or inappropriate management.
RESULTS: Of the 775 patients with a positive TTG, 193 (24.9%, 95% CI 21.9-28.1%) received no follow-up management. We contacted 173 ordering physicians and 120 (69%) responded. Of the 120 responses, 55 patients (45.8%, 95% CI 36.8-55.1%) were managed appropriately and 46 (38.3%, 95% CI 29.7-47.7%) were considered to be inappropriately managed when no repeat TTG was obtained within 18 months. Reasons for inappropriate management included: screen considered to be false positive (44.7%), patient was not experiencing symptoms of celiac disease (31.6%), symptoms had resolved (15.8%), results were not indicative of celiac disease (26.3%) and patients started a gluten-free diet with no evaluation of response (15.8%). In 19 patients the TTG was not acted upon for technical reasons.
CONCLUSIONS: Positive TTGs require appropriate interventions. These include: subspecialist referral for further evaluation and/or repeat testing to evaluate: 1) treatment response or 2) patients with minimal or no symptoms.

PMID: 31324159 [PubMed - in process]

Hematologic Manifestations in Celiac Disease-A Practical Review.

Hematologic Manifestations in Celiac Disease-A Practical Review.

Medicina (Kaunas). 2019 Jul 15;55(7):

Authors: Balaban DV, Popp A, Ionita Radu F, Jinga M

Abstract
Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD can also involve other organs and manifest as an extraintestinal disease. Among the extraintestinal features of CD, hematologic ones are rather frequent and consist of anemia, thrombocytosis (thrombocytopenia also, but rare), thrombotic or hemorrhagic events, IgA deficiency, hyposplenism, and lymphoma. These hematologic alterations can be the sole manifestation of the disease and should prompt for CD testing in a suggestive clinical scenario. Recognition of these atypical, extraintestinal presentations, including hematologic ones, could represent a great opportunity to increase the diagnostic rate of CD, which is currently one of the most underdiagnosed chronic digestive disorders worldwide. In this review, we summarize recent evidence regarding the hematological manifestations of CD, with focus on practical recommendations for clinicians.

PMID: 31311098 [PubMed - in process]

Clinical manifestations and gastrointestinal pathology in 40 patients with autoimmune enteropathy.

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Clinical manifestations and gastrointestinal pathology in 40 patients with autoimmune enteropathy.

Clin Immunol. 2019 Jul 04;:

Authors: Villanacci V, Lougaris V, Ravelli A, Buscarini E, Salviato T, Lionetti P, Salemme M, Martelossi S, De Giacomo C, Falchetti D, Pelizzo G, Bassotti G

Abstract
Autoimmune enteropathy (AIE) is a rare condition that may affect pediatric and adult patients, frequently associated with primary immunodeficiencies. We performed a retrospective study on clinical and histological findings from 40 AIE patients. Histological presentation showed a prevalent celiac disease pattern (50%), followed by the mixed pattern (35%), independently of age, chronic active duodenitis (10%), and GVHD-like pattern (5%). Patients with primary immunodeficiencies (24/40) presented mainly with the celiac disease pattern (72.2% versus 22.2%; p < .0001), while patients without primary immunodeficiencies presented with a mixed histological pattern (61.1% versus 13.6%; p < .0001). Our study shows that the prevalent histological presentation is the celiac disease-like pattern, independently of age, and, for the first time, that the histological presentation of AIE differs significantly between patients with and without primary immunodeficiencies. These findings may be helpful for more precise and timely diagnosis and management of this rare disorder.

PMID: 31279857 [PubMed - as supplied by publisher]

The role of mast cells in pediatric gastrointestinal disease.

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The role of mast cells in pediatric gastrointestinal disease.

Ann Gastroenterol. 2019 Jul-Aug;32(4):338-345

Authors: Ravanbakhsh N, Kesavan A

Abstract
Mast cells are granulocytes derived from CD34+ pluripotent progenitor cells that demonstrate plasticity in their development, leaving the bone marrow and differentiating in the tissue where they ultimately reside. They are best known for their role in the allergic response, but also play a prominent immunoregulatory role in other processes, including immune tolerance, the innate immune response, angiogenesis, wound healing and tissue remodeling. Mast cells are found throughout the gastrointestinal tract; their metabolic products influence and regulate intestinal epithelial and endothelial function, gastrointestinal secretion, intestinal motility and absorption, and contribute to host defense. They also play an important role in the development of visceral hypersensitivity through bidirectional interaction with the enteric nervous system. Mast cells have been found to have an increasingly important role in the pathophysiology of a number of pediatric gastrointestinal diseases. This review summarizes the current understanding of the role that mast cells play in the development of pediatric gastrointestinal disorders, including eosinophilic esophagitis, functional dyspepsia, irritable bowel syndrome, celiac disease, inflammatory bowel disease, histologically negative appendicitis, Hirschsprung's disease, intestinal neuronal dysplasia, and food protein-induced enterocolitis syndrome.

PMID: 31263355 [PubMed]

Duodenal Biopsies Classification and Understanding using Convolutional Neural Networks.

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Duodenal Biopsies Classification and Understanding using Convolutional Neural Networks.

AMIA Jt Summits Transl Sci Proc. 2019;2019:453-461

Authors: Al Boni M, Syed S, Ali A, Moore SR, Brown DE

Abstract
Environmental Enteropathy (EE) and celiac disease (CD) are gastrointestinal conditions that adversely impact the growth of children. EE is prevalent in low- and middle-income countries, whereas as CD is prevalent worldwide. The histologic appearance of duodenal EE biopsies significantly overlaps with celiac enteropathy. We propose a convolutional neural network (ConvNet) to classify EE cases from Pakistani infants along with celiac and healthy controls from the United States. We also identified areas of biopsies that generate high activation values in the ConvNet model. The identified features helped in distinguishing EE and celiac from healthy intestinal tissues. This work advances the understanding of both diseases and provides a potential screening and diagnostic tool for practitioners.

PMID: 31258999 [PubMed]

IL10 promoter haplotypes may contribute to altered cytokine expression and systemic inflammation in celiac disease.

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IL10 promoter haplotypes may contribute to altered cytokine expression and systemic inflammation in celiac disease.

Clin Immunol. 2018 05;190:15-21

Authors: Hofmann SR, Laass MW, Fehrs A, Schuppan D, Zevallos VF, Salminger D, Mäbert K, Hedrich CM

Abstract
Celiac disease (CD) is an autoimmune/inflammatory condition triggered by dietary gluten intake in genetically predisposed individuals. Though associations with MHC class II HLA-DQ2 or -DQ8 are the primary and necessary genetic predisposition for CD, >97% of genetically predisposed individuals never develop CD. Cytokines were measured in the serum of CD patients and controls. Possible associations with IL10 promoter variants were investigated. Cytokine expression from PBMCs was monitored in response to gluten exposure, or CD3/TCR complex stimulation in the absence or presence of recombinant IL-10. Serum cytokines varied between patients with CD at the time of diagnosis, after dietary elimination of gluten, and healthy controls. Serum IL-17A reflected disease activity. Reduced IL-10 serum levels and altered IL-10 expression by PBMCs coincided with IL10 promoter haplotypes that encode for "low" IL-10 expression (ATA). Increased prevalence of ATA IL10 promoter haplotypes and subsequently reduced IL-10 expression may be an immunological cofactor in individuals genetically predisposed for the development of CD. Resulting cytokine imbalances may be utilized as disease biomarkers in CD.

PMID: 29481982 [PubMed - indexed for MEDLINE]

Celiac disease: What the Indian pediatricians know about the disease.

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Celiac disease: What the Indian pediatricians know about the disease.

Indian J Gastroenterol. 2019 Jun 28;:

Authors: Malik I, Kumar K, Hussain H, Bhatia V, Sibal A, Malhotra S

Abstract
To ascertain the knowledge, awareness, and practices pertaining to celiac disease (CD) among the Indian pediatricians. A survey link containing a questionnaire was shared through electronic mail using a pediatric database. The survey was kept active for 6 months; all responses received at the end of the survey were analyzed. Two hundred and seventy one pediatricians out of more than 10,000 chose to respond to the survey. Most pediatricians agreed that more patients with CD are being diagnosed than earlier. The reasons for higher detection of CD were perceived to be higher index of clinical suspicion by pediatricians (86.7%) followed by increased awareness among parents (45.8%). Most pediatricians opined that clinical manifestations which prompted to a diagnosis of CD were failure to thrive (96.2%) and chronic diarrhea (81.4%). Knowledge about atypical manifestations of celiac disease was low.  Though knowledge about the common association of CD with type 1 diabetes (62.1%) and autoimmune hepatitis (55.8%) was there, awareness about its association with other uncommon conditions was lacking. Though 68% of the pediatricians were of the opinion that the confirmation of diagnosis by a mucosal biopsy is necessary, 26.5% of respondents believed that only a positive serology was sufficient for a diagnosis. A trial of gluten-free diet (GFD) was thought to be a logical step if serology was positive by 31.3% of respondents. While 87.7% of pediatricians advocated lifelong adherence to GFD, 12.3% felt that GFD could be discontinued in the future. This web-based survey revealed that though pediatricians are seeing increasing number of celiac disease patients, there is a need to increase awareness regarding the disease, its associated conditions, the need for mucosal biopsy to confirm the diagnosis and the necessity of lifelong adherence to GFD.

PMID: 31254168 [PubMed - as supplied by publisher]

Micronutrient Deficiencies Are Common in Contemporary Celiac Disease Despite Lack of Overt Malabsorption Symptoms.

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Micronutrient Deficiencies Are Common in Contemporary Celiac Disease Despite Lack of Overt Malabsorption Symptoms.

Mayo Clin Proc. 2019 Jun 12;:

Authors: Bledsoe AC, King KS, Larson JJ, Snyder M, Absah I, Choung RS, Murray JA

Abstract
OBJECTIVE: To evaluate micronutrient deficiencies in a contemporary cohort of adult patients with newly diagnosed celiac disease (CD).
PATIENTS AND METHODS: This is a retrospective study of prospective adults newly diagnosed with CD from January 1, 2000, through October 31, 2014, at Mayo Clinic. Micronutrient data were collected for tissue transglutaminase IgA, zinc, 25-hydroxy vitamin D, ferritin, albumin, copper, vitamin B12, and serum folate. Data were analyzed for absolute number of deficiencies and associations with age, sex, body mass index, presenting symptoms, and tissue transglutaminase IgA; each deficiency was assessed using logistic regression. Deficiencies were compared with age- and sex-matched controls from the National Health and Nutrition Examination Survey.
RESULTS: In total, 309 patients with CD (196 women and 113 men; mean age, 46.1±15.1 years; mean body mass index, 25.9 kg/m2) were included. Weight loss was seen in only 25.2% (78/309) of patients. Zinc was deficient in 59.4% (126/212) of patients with CD compared with 33.2% (205/618) of controls (P<.001). Albumin was low in 19.7% (24/122) compared with 1.1% of controls (P<.001). Copper was low in 6.4% (13/204) compared with 2.1% (13/618) of controls (P=.003). Vitamin B12 was low in 5.3% (13/244) compared with 1.8% (11/618) of controls (P=.004). Folate was low in 3.6% (6/159) compared with 0.3% (2/618) of controls (P=.002). 25-Hydroxy vitamin D was low in 19.0% (44/213) compared with 18% (111/618) of controls (P=.72). Ferritin was low in 30.8% (66/214) of patients; no NHANES controls were available for comparison for ferritin.
CONCLUSION: Micronutrient deficiencies remain common in adults with CD despite increased nonclassic presentation. This study provides support for micronutrient assessment at the time of CD diagnosis.

PMID: 31248695 [PubMed - as supplied by publisher]

Association Between Antibiotics in the First Year of Life and Celiac Disease.

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Association Between Antibiotics in the First Year of Life and Celiac Disease.

Gastroenterology. 2019 06;156(8):2217-2229

Authors: Dydensborg Sander S, Nybo Andersen AM, Murray JA, Karlstad Ø, Husby S, Størdal K

Abstract
BACKGROUND & AIMS: The intestinal microbiota is believed to be involved in the pathogenesis of celiac disease, in addition to genetic variants and dietary gluten. The gut microbiota is strongly influenced by systemic antibiotics-especially in early life. We explored the association between exposure to a systemic antibiotic in the first year of life and risk of diagnosed celiac disease.
METHODS: We performed an observational nationwide register-based cohort study. We included all children born in Denmark from 1995 through 2012 or Norway from 2004 through 2012. Children born in Denmark were followed until May 8, 2015 (age at end of follow-up was 2.3-20.3 years) and children born in Norway were followed until December 31, 2013 (age at end of follow-up was 1-10 years). We collected medical information from more than 1.7 million children, including 3346 with a diagnosis of celiac disease. Exposure to systemic antibiotics was defined as a dispensed systemic antibiotic in the first year of life.
RESULTS: Exposure to systemic antibiotics in the first year of life was positively associated with diagnosed celiac disease in the Danish and Norwegian cohorts (pooled odds ratio 1.26, 95% confidence interval 1.16-1.36). We found a dose-dependent relation between an increasing number of dispensed antibiotics and the risk of celiac disease (pooled odds ratio for each additional dispensed antibiotic 1.08, 95% confidence interval 1.05-1.11). No specific type of antibiotic or age period within the first year of life was prominent. Adjustment for hospital admissions with an infectious disease in the first year of life did not change the estimates; adjustment for the number of maternally reported infections in the child in 2 large sub-cohorts decreased the association slightly (pooled odds ratio 1.18, 95% confidence interval 0.98-1.39).
CONCLUSION: In a nationwide study of children in Denmark and Norway, we found exposure to systemic antibiotics in the first year of life to be associated with a later diagnosis of celiac disease. These findings indicate that childhood exposure to systemic antibiotics could be a risk factor for celiac disease.

PMID: 30836095 [PubMed - indexed for MEDLINE]

Randomized Double-Blind Placebo-Controlled Crossover Trial for the Diagnosis of Non-Celiac Gluten Sensitivity in Children.

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Randomized Double-Blind Placebo-Controlled Crossover Trial for the Diagnosis of Non-Celiac Gluten Sensitivity in Children.

Am J Gastroenterol. 2018 03;113(3):421-430

Authors: Francavilla R, Cristofori F, Verzillo L, Gentile A, Castellaneta S, Polloni C, Giorgio V, Verduci E, DʼAngelo E, Dellatte S, Indrio F

Abstract
OBJECTIVES: Non-celiac gluten sensitivity (NCGS) is characterized by intestinal and extra-intestinal symptoms that are related to the ingestion of gluten in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). In this multicenter study, we aim for the first time to evaluate the prevalence of NCGS in pediatric subjects with chronic functional gastrointestinal symptoms associated with gluten ingestion using a double-blind placebo-controlled (DBPC) gluten challenge with crossover.
METHODS: Among 1,114 children with chronic gastrointestinal symptoms (negative CD and WA), those exhibiting a positive correlation between symptoms and gluten ingestion were eligible for a diagnostic challenge including the following phases: run-in, open gluten-free diet (GFD) and DBPC crossover gluten challenge. Patients were randomized to gluten (10 g/daily) and placebo (rice starch) for 2 weeks each, separated by a washout week. The gluten challenge was considered positive in the presence of a minimum 30% decrease of global visual analogue scale between gluten and placebo.
RESULTS: Out of 1,114 children, 96.7% did not exhibit any correlation with gluten ingestion. Thirty-six children were eligible; after the run-in and open GFD, 28 patients entered the gluten challenge. Eleven children (39.2%; 95% CI: 23.6-53.6%) tested positive.
CONCLUSIONS: This is the first demonstration of the existence of NCGS in children that reinforce the need for a DBPC for the diagnosis as the diagnosis is ruled out in >60% of cases. The registration identifier in ClinicalsTrials.gov is NCT02431585.

PMID: 29380821 [PubMed - indexed for MEDLINE]

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