Recent PubMed Articles on Coeliac Disease (External)

The Environmental Determinants of Diabetes in the Young (TEDDY) Study: 2018 Update.

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The Environmental Determinants of Diabetes in the Young (TEDDY) Study: 2018 Update.

Curr Diab Rep. 2018 10 23;18(12):136

Authors: Rewers M, Hyöty H, Lernmark Å, Hagopian W, She JX, Schatz D, Ziegler AG, Toppari J, Akolkar B, Krischer J, TEDDY Study Group

Abstract
PURPOSE OF REVIEW: The environmental triggers of islet autoimmunity leading to type 1 diabetes (T1D) need to be elucidated to inform primary prevention. The Environmental Determinants of Diabetes in the Young (TEDDY) Study follows from birth 8676 children with T1D risk HLA-DR-DQ genotypes in the USA, Finland, Germany, and Sweden. Most study participants (89%) have no first-degree relative with T1D. The primary outcomes include the appearance of one or more persistent islet autoantibodies (islet autoimmunity, IA) and clinical T1D.
RECENT FINDINGS: As of February 28, 2018, 769 children had developed IA and 310 have progressed to T1D. Secondary outcomes include celiac disease and autoimmune thyroid disease. While the follow-up continues, TEDDY has already evaluated a number of candidate environmental triggers, including infections, probiotics, micronutrient, and microbiome. TEDDY results suggest that there are multiple pathways leading to the destruction of pancreatic beta-cells. Ongoing measurements of further specific exposures, gene variants, and gene-environment interactions and detailed "omics" studies will provide novel information on the pathogenesis of T1D.

PMID: 30353256 [PubMed - indexed for MEDLINE]

Liver pathology in children with newly diagnosed celiac disease.

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Liver pathology in children with newly diagnosed celiac disease.

Clin Exp Hepatol. 2019 May;5(2):129-132

Authors: Kwiatek-Średzińska KA, Kondej-Muszyńska K, Uścinowicz M, Werpachowska I, Sobaniec-Łotowska M, Lebensztejn D

Abstract
Aim of the study: To evaluate the prevalence and the type of liver pathology in children at the time of diagnosis of celiac disease (CD).
Material and methods: Data from newly diagnosed children with CD hospitalized in the university hospital were retrospectively reviewed. Liver pathology was defined as elevated alanine transaminase (ALT) and/or gamma-glutamyl transpeptidase (GGT) serum activity and/or pathological changes of the organ in ultrasound.
Results: Liver pathology was detected in 17 of 149 children (11.4%). Ten patients (6.7%) had an elevated ALT serum activity, whereas no child had an elevated GGT activity. Pathological changes of liver in ultrasound (mainly enlargement or steatosis of the organ) were found in 12 patients (8.1%), of whom 5 children (3.4%) had simultaneously elevated ALT serum activity. Children with liver pathology had lower iron (Fe) (p = 0.02) and folic acid (p = 0.01) concentrations compared to the rest of the patients. There were no statistically significant differences between liver pathology existence and age, sex, serum immunoglobulin A anti-tissue transglutaminase type 2 antibodies (IgA anti-TG2), ferritin, vitamin B12, or vitamin D concentrations. Moreover, a positive correlation between IgA anti-TG2 concentration and ALT serum activity was found (p < 0.01, R = 0.29).
Conclusions: Liver pathology is present at diagnosis in a significant proportion of children with CD in the form of hypertransaminasemia and pathological changes of the organ in ultrasound. There is a correlation between IgA anti-TG2 concentration and ALT serum activity.

PMID: 31501788 [PubMed]

Determinants of glycaemic outcome in the current practice of care for young people up to 21 years old with type 1 diabetes under real-life conditions.

Determinants of glycaemic outcome in the current practice of care for young people up to 21 years old with type 1 diabetes under real-life conditions.

Diabet Med. 2019 Sep 09;:

Authors: Kordonouri O, Lange K, Biester T, Datz N, Kapitzke K, von dem Berge T, Weiskorn J, Danne T

Abstract
AIM: To determine factors influencing the success of treatment for type 1 diabetes, defined as HbA1c < 58 mmol/mol (<7.5%), in a large paediatric cohort under real-life conditions.
METHODS: This is a monocentric observational study analysing the determinants of glycaemic outcome (sex, age, comorbidities, sociodemographic factors, diabetes technology) in an entire cohort of people with diabetes aged up to 21 years. Glycaemic outcome was defined as an individual's median HbA1c and the prevalence of acute complications over this period.
RESULTS: Of 700 young people with type 1 diabetes [age 13.6 years (range: 1.4-20.9 years); diabetes duration 5.8 years (range: 0.1-18.3 years)], 63% were using an insulin pump and 32% any type of continuous glucose monitoring. Mean HbA1c was 61 mmol/mol [95% confidence interval (CI) 60-62; 7.7%, 95% CI 7.5-7.8]. Some 63% of children aged < 12 years reached HbA1c (58 mmol/mol (<7.5%) compared with 43% of older participants. The prevalence of severe hypoglycaemia was 2.41 events and that of diabetic ketoacidosis 1.4 events per 100 person-years. Neither type of insulin therapy nor use of continuous glucose monitoring, sex or comorbidity with coeliac disease or thyroiditis was significantly associated with glycaemic outcome. However, age, diabetes duration, having a father not born in Germany, psychiatric comorbidities and family structure were associated with HbA1c .
CONCLUSIONS: Current technologies and a multidisciplinary team approach allow high numbers of children and adolescents to realize tight glycaemic control with a low prevalence of acute complications. However, age-related challenges, sociodemographic factors and psychological comorbidities are barriers to achieving best possible glycaemic outcome.

PMID: 31498923 [PubMed - as supplied by publisher]

Swedish Inflammatory Bowel Disease Register (SWIBREG) - a nationwide quality register.

Swedish Inflammatory Bowel Disease Register (SWIBREG) - a nationwide quality register.

Scand J Gastroenterol. 2019 Sep 09;:1-13

Authors: Ludvigsson JF, Andersson M, Bengtsson J, Eberhardson M, Fagerberg UL, Grip O, Halfvarson J, Hjortswang H, Jäghult S, Karling P, Nordenvall C, Olén O, Olsson M, Rejler M, Strid H, Myrelid P

Abstract
Background: Inflammatory bowel disease (IBD) is a chronic, inflammatory relapsing disease with increasing incidence. IBD research and long-term follow-up of patients have, however, been hampered by lack of detailed data on disease phenotype, patient-reported outcome measures, Physician Global Assessment, disease activity, and hospital-administered drugs. Aim: To review the Swedish IBD quality register (SWIBREG). Methods: Review of SWIBREG including questionnaire data from users and patients. Results: SWIBREG was launched in 2005, and as of April 2019, contains 46,400 patients with IBD (Crohn's disease: n = 15,705, ulcerative colitis: n = 21,540, IBD unclassified and other colitis (including e.g., microscopic colitis): n = 9155). Of these IBD patients, 7778 had been diagnosed in childhood (16.8%). Earlier research has shown that combining SWIBREG and the Swedish National Patient Register (NPR) yields a positive predictive value of 100% (95%CI = 95-100%) for having a diagnosis of IBD. Moreover, out of all patients in the NPR with a diagnosis of IBD plus either IBD-related surgery or immunomodulatory/biological treatment during the past 18 months, SWIBREG covers 59.0%. SWIBREG records not only information on conventional therapies but also on biological treatment, surgery, smoking, disease activity, patient-reported outcome measures (PROMs), and patient-experienced measures (PREMs). Data are presented through a graphical decision support system. Conclusion: SWIBREG benefits patients with IBD, and offers an ideal opportunity for healthcare personnel and researchers to examine disease phenotype and activity, PROMs/PREMs, and hospital-administered drugs in patients with IBD.

PMID: 31498717 [PubMed - as supplied by publisher]

Non-immunological biomarkers for assessment of villous abnormalities in patients with celiac disease.

Non-immunological biomarkers for assessment of villous abnormalities in patients with celiac disease.

J Gastroenterol Hepatol. 2019 Sep 09;:

Authors: Singh A, Verma AK, Das P, Prakash S, Pramanik R, Nayak B, Datta Gupta S, Sreenivas V, Kumar L, Ahuja V, Makharia GK

Abstract
BACKGROUND: Demonstration of villous abnormalities is an essential component of diagnosis of celiac disease (CeD) which requires duodenal biopsies. There is a need for non-invasive biomarker(s) which can predict the presence of villous abnormalities.
METHODS: Levels of plasma citrulline, plasma I-FABP, and serum Reg1α were estimated in treatment naïve patients with CeD and controls. The levels of these biomarkers and their cyclical pattern was validated in a predicted model of enteropathy. Optimum diagnostic cutoff values were derived and the results were further validated in a prospective validation cohort.
RESULTS: While level of plasma citrulline was significantly lower, the levels of plasma I-FABP and serum Reg1α were significantly higher in patients with CeD (n=131) in comparison to healthy (n=216) and disease controls (n=133), and their levels reversed after a gluten-free diet. In the model of predicted enteropathy (n=70), a sequential decrease and then increase in the level of plasma citrulline was observed; such a sequential change was not observed with I-FABP and Reg1α. The diagnostic accuracy for prediction of presence of villous abnormality was 89% and 78% if citrulline level was <30μM/L and I-FABP levels was >1100pg/ml, respectively. The results were validated in a prospective validation cohort (n=104) with a sensitivity and specificity of 79.5% and 83.1%, respectively for predicting villous abnormalities of modified Marsh grade >2 at calculated cut-offs values of citrulline and I-FABP.
CONCLUSIONS: Plasma citrulline <30μM/L is the most consistent, highly reproducible non-invasive biomarker which can predict the presence of villous abnormality and has the potential for avoiding duodenal biopsies in 78% patients suspected to have CeD.

PMID: 31498492 [PubMed - as supplied by publisher]

Celiac Disease Autoimmunity and Emotional and Behavioral Problems in Childhood.

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Celiac Disease Autoimmunity and Emotional and Behavioral Problems in Childhood.

Pediatrics. 2019 Sep 06;:

Authors: Wahab RJ, Beth SA, Derks IPM, Jansen PW, Moll HA, Kiefte-de Jong JC

Abstract
BACKGROUND AND OBJECTIVES: Celiac disease (CeD) is associated with psychopathology in children. It is unknown whether this association is present in children with celiac disease autoimmunity (CDA) identified by screening. We examined the associations between subclinical CDA and emotional and behavioral problems in children without previous CeD diagnosis.
METHODS: In a population-based cohort study of 3715 children (median age: 6 years), blood titers of tissue transglutaminase autoantibodies were analyzed. CDA was defined as a measurement of tissue transglutaminase autoantibodies ≥7 U/mL (n = 51). Children with previous CeD diagnosis or children on a gluten-free diet, were excluded. The Child Behavior Checklist (CBCL) was filled in by parents and was used to assess behavioral and emotional problems of children at a median age of 5.9 years. Multiple linear regression models were applied to evaluate the cross-sectional associations between CDA and CBCL scores. Sensitivity analyses were done in a subgroup of children who were seropositive carrying the HLA antigen risk alleles for CeD.
RESULTS: In basic models, CDA was not associated with emotional and behavioral problems on the CBCL scales. After adjustment for confounders, CDA was significantly associated with anxiety problems (β = .29; 95% confidence interval 0.02 to 0.55; P = .02). After exclusion of children who did not carry the HLA-DQ2 and/or HLA-DQ8 risk alleles (n = 4), CDA was additionally associated with oppositional defiant problems (β = .35; 95% confidence interval 0.02 to 0.69). Associations were not explained by gastrointestinal complaints.
CONCLUSIONS: Our results reveal that CDA, especially combined with the HLA-DQ2 and HLA-DQ8 risk alleles, is associated with anxiety problems and oppositional defiant problems. Further research should be used to establish whether behavioral problems are a reflection of subclinical CeD.

PMID: 31492765 [PubMed - as supplied by publisher]

Chapter 5.1.1. Coeliac Disease.

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Chapter 5.1.1. Coeliac Disease.

J Pediatr Gastroenterol Nutr. 2018 04;66 Suppl 1:S57-S58

Authors: Maki M, Mearin ML, Polanco I, Schmitz J, Troncone R

PMID: 29596167 [PubMed - indexed for MEDLINE]

Score Based Diagnostic Approach to Coeliac Disease and Bone Mineral Density.

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Score Based Diagnostic Approach to Coeliac Disease and Bone Mineral Density.

Pediatr Int. 2019 Sep 05;:

Authors: Coşkun ME, Hizli Ş, Yavuz S, Temel MT

Abstract
OBJECTIVES: We aimed to test the performance of score based diagnostic approach (SBDA) proposed in European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 2012 guideline and to search the usefulness of bone mineral density (BMD) measurement in SBDA as an objective finding in the diagnosis of coeliac disease (CD).
METHODS: The SBDDA scores of 153 biopsy proven coeliac diagnosed children (derived from symptomatology, serology, HLA analysis, histologic) were calculated. Additionally, BMD Z scores of children obtained at diagnosis were also investigated. The diagnostic sensitivity of SBDA was tested in different scenarios in which low BMD was scored as a diagnostic finding.
RESULTS: The mean age of children was 9.48±3.59 years and 54.2% of them were female. All patients got 4 or more which is the minimum score to diagnose CD in SBDA. The mean BMD Z scores of 142 out of 153 patients was -2.70±1.16 and 73.9% of them were below -2. Moreover, different diagnostic scenarios without histology were tested. In one of them, BMD and HLA were not included and the sensitivity was 85.2%. In another one, low BMD was scored as an equivalent of malabsorption, HLA was not included and sensitivity was found 97.2%. The sensitivities of these scenarios were statistically different (p=0,001) CONCLUSION: In the absence of both HLA and histology, accepting low BMD as an equivalent of malabsorption has drastically increased the diagnostic sensitivity while the offered SBDA has showed a limited success. Therefore, BMD might be useful where HLA and biopsy are not available. This article is protected by copyright. All rights reserved.

PMID: 31486579 [PubMed - as supplied by publisher]

Screening of monogenic autoimmune diabetes among children with type 1 diabetes and multiple autoimmune diseases: is it worth doing?

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Screening of monogenic autoimmune diabetes among children with type 1 diabetes and multiple autoimmune diseases: is it worth doing?

J Pediatr Endocrinol Metab. 2019 Sep 04;:

Authors: Strakova V, Elblova L, Johnson MB, Dusatkova P, Obermannova B, Petruzelkova L, Kolouskova S, Snajderova M, Fronkova E, Svaton M, Lebl J, Hattersley AT, Sumnik Z, Pruhova S

Abstract
Background Paediatric type 1 diabetes (T1D) and rare syndromes of monogenic multi-organ autoimmunity share basic features such as full insulin dependency and the presence of circulating beta-cell autoantibodies. However, the aetiopathogenesis, natural course and treatment of these conditions differ; therefore, monogenic multi-organ autoimmunity requires early recognition. We aimed to search for these monogenic conditions among a large cohort of children with T1D. Methods Of 519 children with T1D followed-up in a single centre, 18 had multiple additional autoimmune conditions - either autoimmune thyroid disease (AITD) and coeliac disease (CD) or at least one additional organ-specific autoimmune condition in addition to AITD or CD. These 18 children were tested by direct Sanger sequencing (four patients with a suggestive phenotype of immune dysregulation, polyendocrinopathy, enteropathy, X-linked [IPEX] or signal transducer and activator of transcription 3 [STAT3]- and cytotoxic T-lymphocyte protein 4 [CTLA4]-associated syndromes) or by whole-exome sequencing (WES) focused on autoimmune regulator (AIRE), forkhead box protein 3 (FOXP3), CTLA4, STAT3, signal transducer and activator of transcription 1 (STAT1), lipopolysaccharide-responsive and beige-like anchor protein (LRBA) and interleukin-2 receptor subunit α (IL2RA) genes. In addition, we assessed their T1D genetic risk score (T1D-GRS). Results We identified novel variants in FOXP3, STAT3 and CTLA4 in four cases. All patients had a severe phenotype suggestive of a single gene defect. No variants were identified in the remaining 14 patients. T1D-GRS varied among the entire cohort; four patients had scores below the 25th centile including two genetically confirmed cases. Conclusions A monogenic cause of autoimmune diabetes was confirmed only in four patients. Genetic screening for monogenic autoimmunity in children with a milder phenotype and a combination of AITD and CD is unlikely to identify a monogenic cause. In addition, the T1D-GRS varied among individual T1D patients.

PMID: 31483759 [PubMed - as supplied by publisher]

Deranged regulatory T-cells and transforming growth factor-β1 levels in type 1 diabetes patients with associated autoimmune diseases.

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Deranged regulatory T-cells and transforming growth factor-β1 levels in type 1 diabetes patients with associated autoimmune diseases.

J Postgrad Med. 2017 Jul-Sep;63(3):176-181

Authors: Kaur N, Minz RW, Bhadada SK, Dayal D, Singh J, Anand S

Abstract
AIM: This study was designed to enumerate regulatory T-cells (Tregs) and estimate transforming growth factor-β1 (TGF-β1) levels in type 1 diabetic (T1D) patients with respect to disease duration and associated autoimmune diseases.
METHODS: One hundred and fifty patients and twenty healthy controls were recruited in the study. The patients were subcategorized into eight categories on the basis of disease duration (new onset [NO] and long standing [LS]) and associated diseases, i.e., celiac disease (CD) and autoimmune thyroid disease (AiTD). Treg cells were assessed as CD4+ CD25hi+, FOXP3+ cells and serum TGF-β1 levels were assessed by ELISA.
RESULTS: The frequency of Tregs and levels of TGF-β1 were significantly increased in the patients compared to the healthy controls. Among the different categories of the patients, no significant differences were seen for TGF- β1 levels, but for Tregs in patients with T1D and AiTD (P = 0.035). A significant correlation was also found between percentage count of Tregs and TGF-β1 levels in NO cases in all disease subcategories, but not in LS patients.
CONCLUSION: Thus, there was an increased percentage of Tregs and serum levels of TGF-β1 in T1D patients, irrespective of the disease duration and associated autoimmune diseases. The significant correlation in these two parameters at the onset of the disease, but not in LS disease, indicates that the immunological milieu in LS autoimmune diseases is more complicated with disease-associated conditions such as prolonged hyperglycemia, insulin therapy, and/or continued gluten in diet. Treatment and modulation of these long-term complications for improving immunological parameters require further research.

PMID: 28695870 [PubMed - indexed for MEDLINE]

Intestinal Permeability and IgA Provoke Immune Vasculitis Linked to Cardiovascular Inflammation.

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Intestinal Permeability and IgA Provoke Immune Vasculitis Linked to Cardiovascular Inflammation.

Immunity. 2019 Aug 21;:

Authors: Noval Rivas M, Wakita D, Franklin MK, Carvalho TT, Abolhesn A, Gomez AC, Fishbein MC, Chen S, Lehman TJ, Sato K, Shibuya A, Fasano A, Kiyono H, Abe M, Tatsumoto N, Yamashita M, Crother TR, Shimada K, Arditi M

Abstract
Recent experimental data and clinical, genetic, and transcriptome evidence from patients converge to suggest a key role of interleukin-1β (IL-1β) in the pathogenesis of Kawasaki disease (KD). However, the molecular mechanisms involved in the development of cardiovascular lesions during KD vasculitis are still unknown. Here, we investigated intestinal barrier function in KD vasculitis and observed evidence of intestinal permeability and elevated circulating secretory immunoglobulin A (sIgA) in KD patients, as well as elevated sIgA and IgA deposition in vascular tissues in a mouse model of KD vasculitis. Targeting intestinal permeability corrected gut permeability, prevented IgA deposition and ameliorated cardiovascular pathology in the mouse model. Using genetic and pharmacologic inhibition of IL-1β signaling, we demonstrate that IL-1β lies upstream of disrupted intestinal barrier function, subsequent IgA vasculitis development, and cardiac inflammation. Targeting mucosal barrier dysfunction and the IL-1β pathway may also be applicable to other IgA-related diseases, including IgA vasculitis and IgA nephropathy.

PMID: 31471109 [PubMed - as supplied by publisher]

Characterisation of clinical and immune reactivity to barley and rye ingestion in children with coeliac disease.

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Characterisation of clinical and immune reactivity to barley and rye ingestion in children with coeliac disease.

Gut. 2019 Aug 28;:

Authors: Hardy MY, Russell AK, Pizzey C, Jones CM, Watson KA, La Gruta NL, Cameron DJ, Tye-Din JA

Abstract
OBJECTIVE: Barley and rye are major components of the Western diet, and historic feeding studies indicate that they cause clinical effects in patients with coeliac disease (CD). This toxicity has been attributed to sequence homology with immunogenic wheat sequences, but in adults with CD, these cereals stimulate unique T cells, indicating a critical contribution to gluten immunity independent of wheat. Clinical and immune feeding studies with these grains in children with CD are sparse. We undertook a barley and rye feeding study to characterise the clinical and T-cell responses in children with CD.
DESIGN: 42 children with human leucocyte antigen (HLA)-DQ2.5+ (aged 3-17 years) consumed barley or rye for 3 days. Blood-derived gluten-specific T cells were tested for reactivity against a panel of barley (hordein) and rye (secalin) peptides. Hordein and secalin-specific T-cell clones were generated and tested for grain cross-reactivity. T-cell receptor sequencing was performed on sorted single cells. T-cell responses were compared with those observed in adults with CD.
RESULTS: 90% of the children experienced adverse symptoms, mostly GI, and 61% had detectable gluten-specific T-cell responses targeting peptides homologous to those immunogenic in adults. Deamidation was important for peptide reactivity. Homozygosity for HLA-DQ2.5 predicted a stronger T-cell response. Gluten-specific T cells showed striking similarities in their cross-reactivity between children and adults.
CONCLUSIONS: Barley and rye induce a consistent range of clinical and T-cell responses in children with CD. The findings highlight the importance of a series of dominant hordein and secalin peptides pathogenic in children with CD, some independent of wheat, which closely correspond to those seen in adults.

PMID: 31462555 [PubMed - as supplied by publisher]

Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease.

Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease.

Sci Adv. 2019 Aug;5(8):eaaw7756

Authors: Goel G, Tye-Din JA, Qiao SW, Russell AK, Mayassi T, Ciszewski C, Sarna VK, Wang S, Goldstein KE, Dzuris JL, Williams LJ, Xavier RJ, Lundin KEA, Jabri B, Sollid LM, Anderson RP

Abstract
Celiac disease (CeD), caused by immune reactions to cereal gluten, is treated with gluten -elimination diets. Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. To test whether gluten exposure leads to systemic cytokine production time -related to symptoms, series of multiplex cytokine measurements were obtained in CeD patients after gluten challenge. Peptide injection elevated at least 15 plasma cytokines, with IL-2, IL-8, and IL-10 being most prominent (fold-change increase at 4 hours of 272, 11, and 1.2, respectively). IL-2 and IL-8 were the only cytokines elevated at 2 hours, preceding onset of symptoms. After gluten ingestion, IL-2 was the earliest and most prominent cytokine (15-fold change at 4 hours). Supported by studies of patient-derived gluten-specific T cell clones and primary lymphocytes, our observations indicate that gluten-specific CD4+ T cells are rapidly reactivated by antigen -exposure likely causing CeD-associated gastrointestinal symptoms.

PMID: 31457091 [PubMed - in process]

Response to Golfeyz.

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Response to Golfeyz.

Am J Gastroenterol. 2018 08;113(8):1256-1257

Authors: Lebwohl B, Ludvigsson JF

PMID: 29915398 [PubMed - indexed for MEDLINE]

Peripheral nerve disease secondary to systemic conditions in children.

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Peripheral nerve disease secondary to systemic conditions in children.

Ther Adv Neurol Disord. 2019;12:1756286419866367

Authors: Wilmshurst JM, Ouvrier RA, Ryan MM

Abstract
This review is an overview of systemic conditions that can be associated with peripheral nervous system dysfunction. Children may present with neuropathic symptoms for which, unless considered, a causative systemic condition may not be recognized. Similarly, some systemic conditions may be complicated by comorbid peripheral neuropathies, surveillance for which is indicated. The systemic conditions addressed in this review are critical illness polyneuropathy, chronic renal failure, endocrine disorders such as insulin-dependent diabetes mellitus and multiple endocrine neoplasia type 2b, vitamin deficiency states, malignancies and reticuloses, sickle cell disease, neurofibromatosis, connective tissue disorders, bowel dysmotility and enteropathy, and sarcoidosis. In some disorders presymptomatic screening should be undertaken, while in others there is no benefit from early detection of neuropathy. In children with idiopathic peripheral neuropathies, systemic disorders such as celiac disease should be actively excluded. While management is predominantly focused on symptomatic care through pain control and rehabilitation, some neuropathies improve with effective control of the underlying etiology and in a small proportion a more targeted approach is possible. In conclusion, peripheral neuropathies can be associated with a diverse range of medical conditions and unless actively considered may not be recognized and inadequately managed.

PMID: 31447934 [PubMed]

Progression of Celiac Disease in Children With Antibodies Against Tissue Transglutaminase and Normal Duodenal Architecture.

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Progression of Celiac Disease in Children With Antibodies Against Tissue Transglutaminase and Normal Duodenal Architecture.

Gastroenterology. 2019 08;157(2):413-420.e3

Authors: Auricchio R, Mandile R, Del Vecchio MR, Scapaticci S, Galatola M, Maglio M, Discepolo V, Miele E, Cielo D, Troncone R, Greco L

Abstract
BACKGROUND & AIMS: Potential celiac disease is characterized by positive results from serologic tests for tissue transglutaminase antibodies (anti-TG2) but normal duodenal architecture (Marsh stages 0-1). There is controversy over the best way to manage these patients. We investigated risk factors associated with the development of villous atrophy in children with potential celiac disease.
METHODS: We performed a prospective study of 280 children (ages 2-18 years) in Italy with suspected celiac disease, followed for up to 12 years (range, 18-150 months; median 60 months). The subjects had 2 consecutive positive results from tests for anti-TG2, tested positive for the endomysial antibody (anti-EMA), had total serum levels of immunoglobulin A in the normal range, normal duodenal architecture (Marsh stages 0-1) in 5 biopsies, and HLA DQ2- or DQ8-positive haplotypes. The children underwent serologic tests and clinical analyses every 6 months and a small bowel biopsy was taken every 2 years. A total of 210 patients of the original cohort were assessed at the 9-year follow-up evaluation. We performed multivariate analyses of clinical, genetic, and histologic data to identify factors associated with progression to villous atrophy.
RESULTS: During the follow-up period, 42 (15%) of 280 children developed villous atrophy, whereas 89 (32%) children no longer tested positive for anti-TG2 or anti-EMA. The cumulative incidence of progression to villous atrophy was 43% at 12 years. In multivariate analysis, the baseline factors most strongly associated with development of villous atrophy were numbers of γδ intraepithelial lymphocyte cells followed by age and homozygosity for the HLA DQB1*02. In discriminant analysis, these baseline factors identified 80% of the children who developed baseline atrophy.
CONCLUSIONS: In a long-term study of 280 children with suspected celiac disease (based on anti-TG2 and anti-EMA) on gluten-containing diets, the cumulative incidence of progression to villous atrophy was 43% over a 12-year period. We identified factors that can be used to identify children at highest risk for villous atrophy. This approach might be used to determine whether children with suspected celiac disease should immediately start a gluten-free diet or be monitored on their regular diet.

PMID: 30978358 [PubMed - indexed for MEDLINE]

Lower HbA1c in patients with type 1 diabetes and celiac disease who reached celiac-specific antibody-negativity - a multicenter DPV analysis.

Lower HbA1c in patients with type 1 diabetes and celiac disease who reached celiac-specific antibody-negativity - a multicenter DPV analysis.

Pediatr Diabetes. 2019 Aug 20;:

Authors: Nagl K, Bollow E, Liptay S, Rosenbauer J, Koletzko S, Pappa A, Näke A, Fröhlich-Reiterer E, Döring C, Wolf J, Salfeld P, Prinz N

Abstract
OBJECTIVES: To study celiac-specific antibody status over three years in patients with type 1 diabetes and biopsy-proven celiac disease (T1D + CD). Further, to determine clinical differences after diagnosis between patients reaching constant antibody-negativity (Ab-neg) and staying antibody-positive (Ab-pos).
METHODS: 608 pediatric T1D + CD patients from the multicenter DPV registry were studied longitudinally regarding their CD-specific antibody-status. Differences between Ab-neg (n = 218) and Ab-pos (n = 158) patients three years after biopsy were assessed and compared with 26 833 T1D patients without CD by linear and logistic regression adjusted for age, gender, diabetes duration and migration background.
RESULTS: 36% of T1D + CD patients reached and sustained antibody-negativity three years after CD diagnosis. The median time until patients returned to Ab-neg was 0.86 (0.51;1.16) years. Three years after diagnosis, HbA1c was lowest in Ab-neg and highest in Ab-pos patients compared to T1D-only patients (adjusted mean (95%CI): 7.72 (7.51-7.92) % vs 8.44 (8.20-8.68) % vs 8.19 (8.17-8.21) %, adjusted P < 0.001, respectively). Total cholesterol, LDL-cholesterol and frequency of dyslipidemia were significantly lower in Ab-neg compared to T1D-only patients (167 (161-173) mg/dl vs 179 (178-179) mg/dl, P < 0.001; 90 (84-96) mg/dl vs 99 (98-99) mg/dl, P = 0.005; 15.7 (10.5-22.9)% vs 25.9 (25.2-26.6)%, P = 0.017). In longitudinal analyses over six years after diagnosis, a constantly higher HbA1c (P < 0.001) and a lower height-SDS (P = 0.044) was observed in Ab-pos compared to Ab-neg patients.
CONCLUSION: Only one third of T1D + CD-patients reached constant Ab-negativity after CD-diagnosis. Achieving Ab-negativity after diagnosis seems to be associated with better metabolic control and growth, supposedly due to a higher adherence to therapy in general. This article is protected by copyright. All rights reserved.

PMID: 31430021 [PubMed - as supplied by publisher]

[The extraintestinal spectrum of gluten sensitivity].

[The extraintestinal spectrum of gluten sensitivity].

Orv Hetil. 2019 Aug;160(34):1327-1334

Authors: Fedor I, Zöld É, Barta Z

Abstract
Although celiac disease (gluten-sensitive enteropathy) is a relatively well known malady, yet is surrounded by several misconceptions. It is in fact, a multi-systemic autoimmune disorder with a wide spectrum of possible presentations, though most clinicians regard it as a solely gastrointestinal disease. Another misconception that it is a disease of paediatric age group. Thus, the diagnosis of adult or elderly patients is often delayed. Recognition of the disease in the adults can be challenging, as there are less pronounced gastrointestinal symptoms, and patients present with other manifestations (i.e., neurologic, cardiovascular, hepatobiliary, or hematologic involvement are common). As these extraintestinal manifestations are less well known among practicing physicians, here we propose a brief overview of these. We aimed to summarize the available literature on the extraintestinal manifestations associated with gluten sensitivity. Orv Hetil. 2019; 160(34): 1327-1334.

PMID: 31423827 [PubMed - in process]

The evolution of celiac disease publications: a holistic approach with bibliometric analysis.

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The evolution of celiac disease publications: a holistic approach with bibliometric analysis.

Ir J Med Sci. 2019 Aug 17;:

Authors: Demir E, Comba A

Abstract
BACKGROUND: Despite the increasing number of publications on celiac disease, there is a lack of studies that made a holistic bibliometric evaluation of the studies on this topic.
AIMS: The purpose of this study is to analyze the publications about celiac disease by using bibliometric methods and this way to demonstrate the celiac disease-related trends, top effective articles, journals, and international collaborations between the countries and institutions.
METHODS: All articles published between 1980 and 2018 on celiac disease were downloaded from Web of Science and analyzed with bibliometric methods. The correlations between economic development and publication productivity of the countries were investigated with Spearman's rank correlation coefficient. Linear regression analysis was used to estimate the number of publications and citations.
RESULTS: The literature review showed that there were 6545 articles about celiac disease published between the years 1980 and 2018. The top productive country that produced most publications about celiac disease was the Italy. The most prolific journals were the Journal of Pediatric Gastroenterology and Nutrition and Scandinavian Journal of Gastroenterology. There was a moderate positive significant correlation between the number of publications and gross domestic product (r = 0.639, p < 0.001).
CONCLUSIONS: Despite the advanced research on the diagnosis, pathophysiology, and treatment of celiac disease, the global research level about the disease is low. Therefore, the international collaboration about the disease should not remain at only regional contexts; the exchange of knowledge and common studies especially in developing or underdeveloped countries should be supported in terms of prevalence and clinic studies.

PMID: 31422546 [PubMed - as supplied by publisher]

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