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Non-nutritional factors are involved in bone cells dystunction in celiac disease
from the distal duodenum using an endoscope. Frequently, these biopsies are too small or poorly oriented to enable optimal diagnos=s.We investigated whether large and oriented jejunal biopsies can be obtained endoscopically. Methods: In patients suspected of CD (mainly diarrhea and weight loss) we performed an upper endoscopy using a colonoscope with large working channel enabling passage of a large-capacity forceps, after sedation with midazolam. Four jejunal and 4 duodenal biopsies were obtained under direct vision. The biopsies were carefully oriented on a strip paper. Histopathological evaluation and histomorphometry using a CD3 marker were performed. In the first 30 patients we confirmed that the colonoscope was positioned beyond Treitz ligament by fluoroscopy. The complications and failures to reach the jejunum were recorded. Results: In a 2-year period we investigated 145 patients. No major complications occurred, although 3 patients experienced moderate pain despite midazolam. The jejunum was reached in 141/145 patients (97%); reasons for failure were inability to advancethe forceps (n = 1), esophagealstenosis (n = 1) and uncorrectable looping in the stomach (n = 2). Histopathology revealed a mean biopsy size of 5 mm, with adequate to excellent orientation in all, enabling assessment of crypts and villous anatomy as well as crypt/villns ratio. Marsh I-II lesions were found in 55 (38%) and Marsh III in 15 patients (10%). Duodenal and jejunal biopsies were concordant in 53/55 (96%) patients with Marsh HI and in 10/10 patients with Marsh II1. In 2 patients duodenal biopsies were normal, but jejunum showed Marsh I-II, Conclusions: The use of large-capacity forceps and ofienfation of biopsies on strip paper allowed excellent histopathological examination in all patients. Using a colonoscope, the jejunum can be reached in almost all patients. Duodenal biopsies were sufficient to diagnose CD in virtually all patients. Thus, jejunal biopsies should be considered only in case of very high clinical suspicion despite normal duodenal biopsies.
RESULTS: from 1.11.1997 to 30.6.2000, of 4.017 patiens screened, 72 new cases of CD were diagnosed, who came from: Hemato-oncology (5), Obstetric and Gynaecology (6), Endocrinology(6), Dermatology(4), ~ephrology(4), Gastroenterology (18), GeneralPractioners (12) and Pediatricians (12). Celiac disease prevalence in the South of Italy in a risk population is of 1/54. CONCLUSIONS: in our opinion the above screening program for diseases likely to be correlated with CD favors a more rapid, clearer detection of patients with misdiagnosed CD at a minor cost, and with better results compared to a mass screening programm. 2016 Non-Nutritional Factors Are Involved In Bone Cells Dysfunction in Celiac Disease Graziano Barera, Pediatric Dept, Scientific Institute H S Raffaele, Milan Italy; Isabella Villa, Bone Metabolic Unit, Scientific Institute H S Raffaele, Milan Italy; Laura Menni, Cesare Bianchi, Pediatric Dept, Scientific Institute H S Raffaele, Milan Italy; Alessandro Rubinecci, Bone Metabolic Unit, Scientific Institute H S Raffaele, Milan Italy; Stefano Morn, Lab of Pediatric Endocrinology, H S Raffaele, Milan Italy BACKGROUND/OBJECTIVESUntreated celiac disease (CD) is associated with various degrees of osteomalacia or osteoporosis, both in adults and in children. Osteopenia is not always justified by deficit of nutritional factors alone, since it is not correlated to the severity of malnutrition or alteration in calcium metabolism. There is evidence of the importance of local and systemic humoral factors (cytokines, growth factors, tissue-transglutaminase) in the modulation of bone cells activities. Therefore, we hypothesized that circulating factors rather than calcium malabsorption could be involved in the pathogenesis of bone mineral alterations. For this purpose we selected an in vitro model able to minimize the confounding effect of nutritional factors. METHODSWe enrolled 11 prepubertal untreated celiac patients (aged 8.5 _+ 3.0 yrs), 10 celiac patients (aged 10.9 -+ 2.0 yrs) on a gluten-free diet (mean duration 3.9 - 3.4 yrs), and 8 age-matched controls. CD was diagnosed according to the European Society of Paediatrio Gastroenterology Hepatology and Nutrition criteria. In control subjects CD was excluded by mean of negative antiendomysium and anti tissue-traneglutaminase antibodies assay. Cell proliferation was tested on human osteobiest-like cells derived from normal human bone, established in culture by a modification of the Robey and Termine procedure. 24h after subculturing, cells were rinsed in serum-free medium and medium containing either 5% fetal bovine serum, or 5% serum from celiac patients or control subjects. Cells were counted every two days for 14 days with a haemocytometer. RESULTS Cells incubated with serum of untreated celiac patients showed an increased proliferation at the end of the culture period (144898 _+ 35087 cells) compared to cells incubated with serum of control subjects (131427 _+ 31439) or serum from celiac patients on gluten-free diet (108580 -+ 25755; P = 0.041 vs. untreated). CONCLUSIONSSince cuifudng medium, and therefore nutritional support for cultured cells was the same during the study, the different proliferation patterns observed could be likely ascribed to humoral factors present in the sere of tested patients. Since it has been demonstrated that gluten-free diet is pivotal in modifying the CD-related autoimmunity, we suggest that immune or autoimmune factors could be involved in alteration of bone cells activity and in the pathogenesis of CD-associated bone disease. ACKNOWLEDGMENT:study supported by grant from the "B/k Gulden Italia".
2010 RelaUmnklp Between Gactdc Hatisebacter pyIod IMeetie, end Iron Deficiency Anemia in Subjects with Celiac Disease. LuciD Cuoco, Giovanni Cammarota, Regina A. Jorizzo, Luca Santareiii, Antonio Gasbarrini, Massimo Montaito, Giovanni Gasbarrini, Catholic Univ, Rome Italy Background & Aims Iron deficiency anemia is frequent in celiac disease. Recent investigations have identified H. pylori infection as a factor responsible of iron deficiency. We investigated the potential relationship between H. pylori and iron deficiency anemia in patients with celiac disease. Me~ods: We conducted a prospective observational cohort study on celiac patients evaluated for iron deficiency anemia. An upper endoscopy was performed and biopsy specimens of duodenal and gastric mucosa were taken for histological examination and to assess Heiicohacter pylori status. Results The initial data base was 386 subjects. Of these, 24 were excluded because of concomitant potential causes of iron deficiency. Of the 362 enrolled patients H. pylofi was detected in 77 (21%) subjects, of these 55 (71%) had iron deficiency anemia. Among the 285 H. pylori-negative subjects, 81 (28%) showed anemia (P
2017 Parenteral Vitamin D in Newly Diagnosed Coeliao Dfaese - Pfldimkm¥ Analysis of Double Blind Placebo Controlled Study. William E. Fickling, Royal United Hosp, Bath United Kingdom; R Gupta, D Speden, Ashok K. Bhalla, Francis J. Ring, RNHRD, Bath United Kingdom; Duncan A. Robertson, Royal United Hosp, Bath United Kingdom
Trends in Dlagnotls Rate and Clinical Presentation of AduH Celiac Disease: A 25 Year Prospective Study Joe West, Ben P. Palmer, Univ of Nottingham, Nottingham United Kingdom; Geoffrey K. Holmes, Derbyshire Royal Infirmary, Derby United Kingdom; Richard F. Logan, Univ of Nottingham, Nottingham United Kingdom
BACKGROUND.Osteoporosis is common in newly diagnosed CoeliacDiseaseand bone mineral density (BMD) improves on a gluten free diet. We have previously shown that the increase in BMD stops after two years on a gluten free diet(GFD), and BMD remains low. METHODS. We hypothesize that Vitamin D may augment the increase in BMD on starting the GED and have tested this in a double blind placebo controlled study. We present preliminary data after one year of this two year study. Newly diagnosed patients proven by biopsy were included irrespective of baseline 8MD and randomised to choiecalciferol 300,000 units i.m. or normal saline i.m. We excluded patients on HRT for less than one year, prednisoloce, biphosphonates, Vitamin D or excess thyroxine replacement, renal failure, renal calculi, hypercaicuda or clinical osteomalacia. 8MD of the lumbar spine, hip and total body was measured at 0,6,12 and 24 months. Injections of Vitamin D or saline were given at 0 and 12 months. 49 patients have been enrolled, mean age 54 (active 50 yrs vs placebo 59 yrs). RESULTS.46 patients completed one year (active 20, placebo 26). All have shown improvement in jejunal biopsy after 3 months. BMD at the lumbar spine improved in both groups (active 1.3%, placebo 3.5%). BMD of the total hip increased by 2.9% in the active group vs 3.2% on placebo. 27 patients have completed 2 years (active 11, placebo 16), and lumbar spine improved by 8.3% with active treatment and 2.8% with placebo. Total hip improved by 5.5% active and 2.5% placebo. CONCLUSION. These preleminary data confirm an improvement in BMD at the lumbar spine and hip in coeliac patients placed on a gluten free diet. Vitamin D supplementation does not seem to augment this response.
Background - W'ith the advent of accurate serological tests many centers are reporting increasing numbers of Celiac Disease (CO) diagnoses. This could indicate a true increase in incidence or alternatively reflect greater awareness of CD and better diagnostic tests. We have used data prospectively collected over 25 years to examine rate of diagnosis, trend in presentation and changes in severity of illness. Methods - All adults with CD at the 2 District General Hospitals within Southern Derbyshire, UK (population circa 500,000) have been identified at diagnosis and prospectively followed. Data collected includes date of diagnosis, symptoms and signs at presentation and reason for investigation. We analysed the data over 5 quinquenia (1975-99). Routine use of antigliadin antibody and antieodomysial antibody began in 1987 and 1997 respectively. Results - Diagnosis rate and referral due to an incidental anemia increased. Numbers of cases with no or non-specific symptoms decreased. Results are shown in the table. Conclusions - We found a rapidly increasing rate of diagnosis of CD, accelerated with the introduction of accurate serological tests. Severity of illness appears to have declined. These results are explicable in terms of greater awareness and improved diagnostic methods rather than a true increase in incidence, consistent with the concept of the CD "iceberg" being revealed. Trends in demographics,symptomsat presentationand mesonfor referralin 567 adultpatients wilh CD. Number(Percent)
2018 A Comparative Study Of Endoscopic Duodenal And Jejunal Biop,ties In Suspected Celiac Disease Willem J. Thijs, Dept of Gastroenterology, Medicine Spectrum Twerde, Enschede Netherlands; Joop Van Baaden, Dept of Pathology, Medicine Spectrum Tweote, Enschede Netherlands; Nico Van Bentem, Gerard H. Van Olffen, Jeroen J. Kolkman, Dept of Gastroenterology, Medicine Spectrum Twente, Enschede Netherlands
Quinqumlla
Total number of patients
Mean age at diag. nods
Female N(%)
Oiarrh. gee N(%)
None/ non. specific N(%)
Incidental anemia N(%)
75-79
35 55 70 141 266 567 <0.05
41 44 47 50 51 49
25(71) 34(62) 47(67) 108(77) 180(68) 394(70) <0 05
25(71) 33(60) 45(64) 64(45) 97(37) 264(47) <0.05
3(9) 5(9) 10(14) 22(16) 56(21) 96(17) <0.05
1(3) 4(7) 1(1) 19(14) 44(17) 69(12) <0.05
115419 95-99 Total p value*
Introduction: The diagnosis Celiac Disease(CD) is based on histological evaluation of a small bowel biopsy, With a Crosby capsule it was possible to obtain large biopsies with excellent orientation. However, this procedure has several disadvantages (radiation necessity, patient discomfort, failure and complications). Most physicians therefore rely on normal sized biopsies
, ;(2 test for trend
A-394
RESULTS: from 1.11.1997 to 30.6.2000, of 4.017 patiens screened, 72 new cases of CD were diagnosed, who came from: Hemato-oncology (5), Obstetric and Gynaecology (6), Endocrinology(6), Dermatology(4), ~ephrology(4), Gastroenterology (18), GeneralPractioners (12) and Pediatricians (12). Celiac disease prevalence in the South of Italy in a risk population is of 1/54. CONCLUSIONS: in our opinion the above screening program for diseases likely to be correlated with CD favors a more rapid, clearer detection of patients with misdiagnosed CD at a minor cost, and with better results compared to a mass screening programm. 2016 Non-Nutritional Factors Are Involved In Bone Cells Dysfunction in Celiac Disease Graziano Barera, Pediatric Dept, Scientific Institute H S Raffaele, Milan Italy; Isabella Villa, Bone Metabolic Unit, Scientific Institute H S Raffaele, Milan Italy; Laura Menni, Cesare Bianchi, Pediatric Dept, Scientific Institute H S Raffaele, Milan Italy; Alessandro Rubinecci, Bone Metabolic Unit, Scientific Institute H S Raffaele, Milan Italy; Stefano Morn, Lab of Pediatric Endocrinology, H S Raffaele, Milan Italy BACKGROUND/OBJECTIVESUntreated celiac disease (CD) is associated with various degrees of osteomalacia or osteoporosis, both in adults and in children. Osteopenia is not always justified by deficit of nutritional factors alone, since it is not correlated to the severity of malnutrition or alteration in calcium metabolism. There is evidence of the importance of local and systemic humoral factors (cytokines, growth factors, tissue-transglutaminase) in the modulation of bone cells activities. Therefore, we hypothesized that circulating factors rather than calcium malabsorption could be involved in the pathogenesis of bone mineral alterations. For this purpose we selected an in vitro model able to minimize the confounding effect of nutritional factors. METHODSWe enrolled 11 prepubertal untreated celiac patients (aged 8.5 _+ 3.0 yrs), 10 celiac patients (aged 10.9 -+ 2.0 yrs) on a gluten-free diet (mean duration 3.9 - 3.4 yrs), and 8 age-matched controls. CD was diagnosed according to the European Society of Paediatrio Gastroenterology Hepatology and Nutrition criteria. In control subjects CD was excluded by mean of negative antiendomysium and anti tissue-traneglutaminase antibodies assay. Cell proliferation was tested on human osteobiest-like cells derived from normal human bone, established in culture by a modification of the Robey and Termine procedure. 24h after subculturing, cells were rinsed in serum-free medium and medium containing either 5% fetal bovine serum, or 5% serum from celiac patients or control subjects. Cells were counted every two days for 14 days with a haemocytometer. RESULTS Cells incubated with serum of untreated celiac patients showed an increased proliferation at the end of the culture period (144898 _+ 35087 cells) compared to cells incubated with serum of control subjects (131427 _+ 31439) or serum from celiac patients on gluten-free diet (108580 -+ 25755; P = 0.041 vs. untreated). CONCLUSIONSSince cuifudng medium, and therefore nutritional support for cultured cells was the same during the study, the different proliferation patterns observed could be likely ascribed to humoral factors present in the sere of tested patients. Since it has been demonstrated that gluten-free diet is pivotal in modifying the CD-related autoimmunity, we suggest that immune or autoimmune factors could be involved in alteration of bone cells activity and in the pathogenesis of CD-associated bone disease. ACKNOWLEDGMENT:study supported by grant from the "B/k Gulden Italia".
2010 RelaUmnklp Between Gactdc Hatisebacter pyIod IMeetie, end Iron Deficiency Anemia in Subjects with Celiac Disease. LuciD Cuoco, Giovanni Cammarota, Regina A. Jorizzo, Luca Santareiii, Antonio Gasbarrini, Massimo Montaito, Giovanni Gasbarrini, Catholic Univ, Rome Italy Background & Aims Iron deficiency anemia is frequent in celiac disease. Recent investigations have identified H. pylori infection as a factor responsible of iron deficiency. We investigated the potential relationship between H. pylori and iron deficiency anemia in patients with celiac disease. Me~ods: We conducted a prospective observational cohort study on celiac patients evaluated for iron deficiency anemia. An upper endoscopy was performed and biopsy specimens of duodenal and gastric mucosa were taken for histological examination and to assess Heiicohacter pylori status. Results The initial data base was 386 subjects. Of these, 24 were excluded because of concomitant potential causes of iron deficiency. Of the 362 enrolled patients H. pylofi was detected in 77 (21%) subjects, of these 55 (71%) had iron deficiency anemia. Among the 285 H. pylori-negative subjects, 81 (28%) showed anemia (P
2017 Parenteral Vitamin D in Newly Diagnosed Coeliao Dfaese - Pfldimkm¥ Analysis of Double Blind Placebo Controlled Study. William E. Fickling, Royal United Hosp, Bath United Kingdom; R Gupta, D Speden, Ashok K. Bhalla, Francis J. Ring, RNHRD, Bath United Kingdom; Duncan A. Robertson, Royal United Hosp, Bath United Kingdom
Trends in Dlagnotls Rate and Clinical Presentation of AduH Celiac Disease: A 25 Year Prospective Study Joe West, Ben P. Palmer, Univ of Nottingham, Nottingham United Kingdom; Geoffrey K. Holmes, Derbyshire Royal Infirmary, Derby United Kingdom; Richard F. Logan, Univ of Nottingham, Nottingham United Kingdom
BACKGROUND.Osteoporosis is common in newly diagnosed CoeliacDiseaseand bone mineral density (BMD) improves on a gluten free diet. We have previously shown that the increase in BMD stops after two years on a gluten free diet(GFD), and BMD remains low. METHODS. We hypothesize that Vitamin D may augment the increase in BMD on starting the GED and have tested this in a double blind placebo controlled study. We present preliminary data after one year of this two year study. Newly diagnosed patients proven by biopsy were included irrespective of baseline 8MD and randomised to choiecalciferol 300,000 units i.m. or normal saline i.m. We excluded patients on HRT for less than one year, prednisoloce, biphosphonates, Vitamin D or excess thyroxine replacement, renal failure, renal calculi, hypercaicuda or clinical osteomalacia. 8MD of the lumbar spine, hip and total body was measured at 0,6,12 and 24 months. Injections of Vitamin D or saline were given at 0 and 12 months. 49 patients have been enrolled, mean age 54 (active 50 yrs vs placebo 59 yrs). RESULTS.46 patients completed one year (active 20, placebo 26). All have shown improvement in jejunal biopsy after 3 months. BMD at the lumbar spine improved in both groups (active 1.3%, placebo 3.5%). BMD of the total hip increased by 2.9% in the active group vs 3.2% on placebo. 27 patients have completed 2 years (active 11, placebo 16), and lumbar spine improved by 8.3% with active treatment and 2.8% with placebo. Total hip improved by 5.5% active and 2.5% placebo. CONCLUSION. These preleminary data confirm an improvement in BMD at the lumbar spine and hip in coeliac patients placed on a gluten free diet. Vitamin D supplementation does not seem to augment this response.
Background - W'ith the advent of accurate serological tests many centers are reporting increasing numbers of Celiac Disease (CO) diagnoses. This could indicate a true increase in incidence or alternatively reflect greater awareness of CD and better diagnostic tests. We have used data prospectively collected over 25 years to examine rate of diagnosis, trend in presentation and changes in severity of illness. Methods - All adults with CD at the 2 District General Hospitals within Southern Derbyshire, UK (population circa 500,000) have been identified at diagnosis and prospectively followed. Data collected includes date of diagnosis, symptoms and signs at presentation and reason for investigation. We analysed the data over 5 quinquenia (1975-99). Routine use of antigliadin antibody and antieodomysial antibody began in 1987 and 1997 respectively. Results - Diagnosis rate and referral due to an incidental anemia increased. Numbers of cases with no or non-specific symptoms decreased. Results are shown in the table. Conclusions - We found a rapidly increasing rate of diagnosis of CD, accelerated with the introduction of accurate serological tests. Severity of illness appears to have declined. These results are explicable in terms of greater awareness and improved diagnostic methods rather than a true increase in incidence, consistent with the concept of the CD "iceberg" being revealed. Trends in demographics,symptomsat presentationand mesonfor referralin 567 adultpatients wilh CD. Number(Percent)
2018 A Comparative Study Of Endoscopic Duodenal And Jejunal Biop,ties In Suspected Celiac Disease Willem J. Thijs, Dept of Gastroenterology, Medicine Spectrum Twerde, Enschede Netherlands; Joop Van Baaden, Dept of Pathology, Medicine Spectrum Tweote, Enschede Netherlands; Nico Van Bentem, Gerard H. Van Olffen, Jeroen J. Kolkman, Dept of Gastroenterology, Medicine Spectrum Twente, Enschede Netherlands
Quinqumlla
Total number of patients
Mean age at diag. nods
Female N(%)
Oiarrh. gee N(%)
None/ non. specific N(%)
Incidental anemia N(%)
75-79
35 55 70 141 266 567 <0.05
41 44 47 50 51 49
25(71) 34(62) 47(67) 108(77) 180(68) 394(70) <0 05
25(71) 33(60) 45(64) 64(45) 97(37) 264(47) <0.05
3(9) 5(9) 10(14) 22(16) 56(21) 96(17) <0.05
1(3) 4(7) 1(1) 19(14) 44(17) 69(12) <0.05
115419 95-99 Total p value*
Introduction: The diagnosis Celiac Disease(CD) is based on histological evaluation of a small bowel biopsy, With a Crosby capsule it was possible to obtain large biopsies with excellent orientation. However, this procedure has several disadvantages (radiation necessity, patient discomfort, failure and complications). Most physicians therefore rely on normal sized biopsies
, ;(2 test for trend
A-394