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Das P, Vaiphei K, Amarapurkar AD, Sakhuja P, Nada R, Paulose RR, Chaturvedi R, Sekaran A, Kini U, Rastogi A, Kumari N, Pulimood A, Banerjee M, Kinra P, Singh L, Puri A, Pai G, Kochhar R, Dhali GK, Ramakrishna BS, Sood A, Ghoshal UC, Ahuja V, DattaGupta S, Makharia GK, Misra V. Best practices of handling, processing, and interpretation of small intestinal biopsies for the diagnosis and management of celiac disease: A joint consensus of Indian association of pathologists and microbiologists and Indian society of gastroenterology. INDIAN J PATHOL MICR 2021; 64:S8-S31. [PMID: 34135135 DOI: 10.4103/ijpm.ijpm_1405_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
The Indian Association of Pathologists and Microbiologists (IAPM) and Indian Society of Gastroenterology (ISG) decided to make a joint consensus recommendation for handling, processing, and interpretation of SI biopsies for the diagnosis and management of celiac disease (CD) recognizing the inhomogeneous practice of biopsy sampling, orientation, processing, and interpretation. A modified Delphi process was used to develop this consensus document containing a total of 42 statements and recommendations, which were generated by sharing the document draft, incorporating expert's opinion, followed by three cycles of electronic voting as well as a full-day face-to-face virtual ZOOM meeting and review of supporting literature. Of the 42 statements, 7 statements are on small intestinal (SI) biopsy in suspected patients of CD, site and the number of biopsies; 7 on handling, fixative, orientation, processing, and sectioning in pathology laboratories; 2 on histological orientation; 13 statements on histological interpretation and histological grading; 3 on the assessment of follow-up biopsies; 2 statements on gluten-free diet (GFD)-nonresponsive CD; 4 on challenges in the diagnosis of CD; 2 statements each on pathology reporting protocol and training and infrastructure in this area. The goal of this guideline document is to formulate a uniform protocol agreed upon both by the experienced pathologists and gastroenterologists to standardize the practice, improve the yield of small bowel biopsy interpretation, patients' compliance, overall management in CD, and generate unified data for patient care and research in the related field.
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Affiliation(s)
- Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Kim Vaiphei
- Department of Pathology, Post Graduate Institute of Medical Sciences and Research, Chandigarh, India
| | - Anjali D Amarapurkar
- Department of Pathology, Lokmanya Tilak Municipal General Hospital Sion Hospital, Mumbai, Maharashtra, India
| | - Puja Sakhuja
- Department of Pathology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Ritambhra Nada
- Department of Pathology, Post Graduate Institute of Medical Sciences and Research, Chandigarh, India
| | - Roopa Rachel Paulose
- Department of Pathology, School of Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Rachana Chaturvedi
- Department of Pathology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, Maharashtra, India
| | - Anuradha Sekaran
- Department of Pathology, Asian Institute of Gastroenterology and AIG Hospitals, Hyderabad, Telangana, India
| | - Usha Kini
- Department of Pathology, St. John's Medical College, Bangalore, Karnataka, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Niraj Kumari
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Anna Pulimood
- Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Mala Banerjee
- Department of Pathology, KPC Medical College and Hospital and Peerless Hospital, Kolkata, West Bengal, India
| | - Prateek Kinra
- Department of Pathology, Armed Forces Medical College, Pune, Maharashtra, India
| | - Lavleen Singh
- Department of Pathology, Chacha Nehru Bal Chikitsalya, New Delhi, India
| | - AmarenderSingh Puri
- Department of Gastroenterology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Ganesh Pai
- Department of Gastroenterology, Kuwait Hospital, Sharjah, UAE
| | - Rakesh Kochhar
- Department of Gastroenterology, Post Graduate Institute of Medical Sciences and Research, Chandigarh, India
| | - Gopal Krishna Dhali
- Department of Gastroenterology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India
| | - B S Ramakrishna
- Department of Gastroenterology, SRM Institute of Medical Sciences, Chennai, Tamil Nadu, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Uday Chand Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Govind K Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vatsala Misra
- Department of Pathology, MLN Medical College, Allahabad, Uttar Pradesh, India
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Narang V, Jindal A, Singh A, Varun Mehta BG, Sood N, Sood A. Diagnostic utility of multiple site duodenal biopsies in celiac disease. INDIAN J PATHOL MICR 2021; 64:S73-S77. [PMID: 34135142 DOI: 10.4103/ijpm.ijpm_797_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Background Celiac Disease involves the small intestine patchily affecting more frequently the proximal small bowel but the histological changes have been observed till terminal ileum. Of late in addition to D2, the duodenal bulb (D1 region) biopsies have been found helpful in identifying a small group of patients with CD. Therefore, multiple site biopsies are recommended as histological changes are not uniform throughout small intestine. Methods During this present 1.5 years prospective study, we evaluated 84 cases of suspected celiac disease with respect to the light microscopy (D1, D2, and D3 biopsy) and serology (anti tTg and or EMA). Histological examination was done according to Modified Marsh grading system. Results Out of 84 cases with raised anti tTg, the segmental biopsies significantly increased the diagnostic accuracy from 39/44 cases (88.6%) to 43/44 cases (97.7%) and 44/44 cases (100%) when D2 alone, D1 + D2 and D1 + D2 + D3 biopsies were evaluated, respectively. Of the suspected cases of celiac disease patients (tTg > 10 ULN and associated weight loss, diarrhea), additional D3 biopsy increased the diagnostic yield by 2.1%, compared to D1, D2 region biopsy and 6.38% compared to standard D2 biopsy alone. Of the 28 cases (tTg > 10 times ULN + EMA positive and associated weight loss, diarrhea), the potential celiac disease (histologically Type 1/Normal) cases reduced from 28.5% (standard D2 region alone) to 21.4% and 17.8% when additional biopsies were taken from D1 region and D3 region, respectively, and additional D3 biopsy increased the diagnostic yield by 10.8% (compared to standard D2 biopsy alone) and 3.7% (compared to D1 and D2 biopsy). Conclusion We believe multiple sites duodenal biopsies including D3 region biopsies might increase the diagnostic accuracy of adult celiac disease in addition to sensitive and specific serologic tests.
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Affiliation(s)
- Vikarm Narang
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Akriti Jindal
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Aminder Singh
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | | | - Neena Sood
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Ajit Sood
- Department of Gastroentrology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
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Cukrowska B, Sowińska A, Bierła JB, Czarnowska E, Rybak A, Grzybowska-Chlebowczyk U. Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota - Key players in the pathogenesis of celiac disease. World J Gastroenterol 2017; 23:7505-7518. [PMID: 29204051 PMCID: PMC5698244 DOI: 10.3748/wjg.v23.i42.7505] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 07/31/2017] [Accepted: 08/15/2017] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens (HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive (specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiota homeostasis, epithelial layer integrity, and the gut-associated lymphoid tissue with its intraepithelial lymphocytes (IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.
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Affiliation(s)
- Bożena Cukrowska
- Department of Pathology, The Children’s Memorial Health Institute, Warsaw 04-730, Poland
| | - Agnieszka Sowińska
- Department of Pathology, The Children’s Memorial Health Institute, Warsaw 04-730, Poland
| | - Joanna Beata Bierła
- Department of Pathology, The Children’s Memorial Health Institute, Warsaw 04-730, Poland
| | - Elżbieta Czarnowska
- Department of Pathology, The Children’s Memorial Health Institute, Warsaw 04-730, Poland
| | - Anna Rybak
- Department of Gastroenterology, Division of Neurogastroenterology and Motility, Great Ormond Street Hospital, London WC1N 3JH, United Kingdom
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Radmard AR, Hashemi Taheri AP, Salehian Nik E, Kooraki S, Kolahdoozan S, Mirminachi B, Sotoudeh M, Ekhlasi G, Malekzadeh R, Shahbazkhani B. MR enterography in nonresponsive adult celiac disease: Correlation with endoscopic, pathologic, serologic, and genetic features. J Magn Reson Imaging 2017; 46:1096-1106. [DOI: 10.1002/jmri.25646] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Accepted: 01/10/2017] [Indexed: 12/11/2022] Open
Affiliation(s)
- Amir Reza Radmard
- Department of Radiology, Shariati Hospital; Tehran University of Medical Sciences; Tehran Iran
| | | | - Elham Salehian Nik
- Department of Radiology, Shariati Hospital; Tehran University of Medical Sciences; Tehran Iran
| | - Soheil Kooraki
- Department of Radiology, Shariati Hospital; Tehran University of Medical Sciences; Tehran Iran
| | - Shadi Kolahdoozan
- Autoimmune and Motility Disorders of the Gastro-Intestinal Tract Research Center, Digestive Diseases Research Institute; Tehran University of Medical Sciences; Tehran Iran
| | - Babak Mirminachi
- Autoimmune and Motility Disorders of the Gastro-Intestinal Tract Research Center, Digestive Diseases Research Institute; Tehran University of Medical Sciences; Tehran Iran
| | - Masoud Sotoudeh
- Department of Pathology, Shariati Hospital; Tehran University of Medical Sciences; Tehran Iran
| | - Golnaz Ekhlasi
- Autoimmune and Motility Disorders of the Gastro-Intestinal Tract Research Center, Digestive Diseases Research Institute; Tehran University of Medical Sciences; Tehran Iran
| | - Reza Malekzadeh
- Autoimmune and Motility Disorders of the Gastro-Intestinal Tract Research Center, Digestive Diseases Research Institute; Tehran University of Medical Sciences; Tehran Iran
| | - Bijan Shahbazkhani
- Autoimmune and Motility Disorders of the Gastro-Intestinal Tract Research Center, Digestive Diseases Research Institute; Tehran University of Medical Sciences; Tehran Iran
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Mubarak A, Wolters VM, Houwen RHJ, ten Kate FJW. Immunohistochemical CD3 staining detects additional patients with celiac disease. World J Gastroenterol 2015; 21:7553-7557. [PMID: 26140002 PMCID: PMC4481451 DOI: 10.3748/wjg.v21.i24.7553] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 01/08/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether performing immunohistochemical CD3 staining, in order to improve the detection of intra-epithelial lymphocytosis, has an additional value in the histological diagnosis of celiac disease.
METHODS: Biopsies obtained from 159 children were stained by hematoxylin and eosin (HE) and evaluated using the Marsh classification. CD3 staining was subsequently evaluated separately and independently.
RESULTS: Differences in evaluation between the routine HE sections and CD3 staining were present in 20 (12.6%) cases. In 10 (6.3%) patients the diagnosis of celiac disease (Marsh II and III) changed on examination of CD3 staining: in 9 cases, celiac disease had initially been missed on the HE sections, while 1 patient had been over-diagnosed on the routine sections. In all patients, the final diagnosis based on CD3 staining, was concordant with serological results, which was not found previously. In the other 10 (12.3%) patients, the detection of sole intra-epithelial lymphocytosis (Marsh I) improved. Nine patients were found to have Marsh I on CD3 sections, which had been missed on routine sections. Interestingly, the only patient with negative serology had Giardiasis. Finally, in 1 patient with negative serology, in whom Marsh I was suspected on HE sections, this diagnosis was withdrawn after evaluation of the CD3 sections.
CONCLUSION: Staining for CD3 has an additional value in the histological detection of celiac disease lesions, and CD3 staining should be performed when there is a discrepancy between serology and the diagnosis made on HE sections.
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Molina-Infante J, Santolaria S, Montoro M, Esteve M, Fernández-Bañares F. Sensibilidad al gluten no celiaca: una revisión crítica de la evidencia actual. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 37:362-71. [PMID: 24667093 DOI: 10.1016/j.gastrohep.2014.01.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 12/21/2013] [Accepted: 01/16/2014] [Indexed: 12/13/2022]
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Bruins MJ. The clinical response to gluten challenge: a review of the literature. Nutrients 2013; 5:4614-41. [PMID: 24284613 PMCID: PMC3847752 DOI: 10.3390/nu5114614] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 11/01/2013] [Accepted: 11/06/2013] [Indexed: 02/07/2023] Open
Abstract
The aim of this review was to identify, evaluate and summarize all relevant studies reporting on the clinical response to gluten challenge by adult or pediatric patients with suspected or diagnosed coeliac disease (CD) on a gluten-free diet. We evaluated the effect of gluten challenge on changes in symptoms, intestinal mucosa histology, and serum antibodies. A systematic electronic search was performed for studies published as of 1966 using PubMed and Scopus databases. In the reviewed studies, doses ranged from 0.2 to 30 g/day of wheat gluten or comprised a gluten-containing diet. The onset of symptoms upon gluten intake varied largely from days to months and did not parallel serum antibody or histological changes. Within 3 months of gluten challenge, 70%-100% of pediatric CD patients became positive for AGA-IgA and EMA-IgA antibodies and 50%-70% for AGA-IgG. A limited number of trials suggest that no more than half of adult patients developed positive AGA-IgA, EMA-IgA, tTG-IgA or DGP-IgA/IgG titers. Approximately 50%-100% of pediatric and adult patients experienced mucosal relapse of gluten provocation within 3 months, which was preceded by increased mucosal intra-epithelial lymphocytes within several days of challenge. A 3-month high-dose gluten challenge should be suitable to diagnose the majority of CD patients. In some cases prolonged challenge may be needed to verify diagnosis. Combination testing for antibodies and mucosal histology may fasten the diagnosis.
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Affiliation(s)
- Maaike J Bruins
- DSM Biotechnology Center, Alexander Fleminglaan 1, Delft 2613AX, The Netherlands.
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Santolaria S, Dominguez M, Alcedo J, Abascal M, García-Prats MD, Marigil M, Vera J, Ferrer M, Montoro M. [Lymphocytic duodenosis: etiological study and clinical presentations]. GASTROENTEROLOGIA Y HEPATOLOGIA 2013; 36:565-73. [PMID: 24007857 DOI: 10.1016/j.gastrohep.2013.06.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Revised: 05/29/2013] [Accepted: 06/05/2013] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Lymphocytic duodenosis (LD) is a characteristic lesion in the initial phases of celiac disease (CD) but can be associated with many other entities. The aim of this study was to evaluate the prevalence of distinct causes of LD and possible differences in clinical presentation according to etiology. METHODS A retrospective study was performed that included 194 patients diagnosed with LD (more than 25 intraepithelial lymphocytes per 100 epithelial cells). A preestablished strategy to evaluate the cause of the disease was followed that included celiac serology (antitransglutaminase antibodies), HLA-DQ2/DQ8 genotypes, diagnosis of Helicobacter pylori and small intestinal bacterial overgrowth (SIBO). Diagnosis of CD was established on the basis of clinical and histological response to a gluten-free diet in patients with positive serology or compatible findings on HLA-DQ2 (at least one of the alleles) or -DQ8 (both alleles) study. RESULTS The most frequent cause of LD was CD (39%), followed by SBBO (22%), H.pylori (14%), CD and SIBO (12%), and other causes (13%). Most of the patients (83%) had a compatible HLA-DQ2 or -DQ8 genotype. In these patients, the most frequent diagnosis was CD (46%), while in the absence of HLA-DQ2/DQ8, the most frequent diagnoses were SIBO (44%) and H. pylori (22%). CD was the most frequent diagnosis in patients referred for dyspepsia, diarrhea and anemia, while H. pylori was the most frequent diagnosis in patients with abdominal pain. CONCLUSIONS The most common causes of LD in our environment are CD, followed by SIBO and H. pylori infection.
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Affiliation(s)
- Santos Santolaria
- Unidad de Gastroenterología y Hepatología, Hospital San Jorge, Huesca, España.
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Gujral N, Freeman HJ, Thomson ABR. Celiac disease: prevalence, diagnosis, pathogenesis and treatment. World J Gastroenterol 2012; 18:6036-59. [PMID: 23155333 PMCID: PMC3496881 DOI: 10.3748/wjg.v18.i42.6036] [Citation(s) in RCA: 397] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Revised: 07/27/2012] [Accepted: 08/03/2012] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either "typical" or "atypical". In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture.
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Santolaria S, Alcedo J, Cuartero B, Diez I, Abascal M, García-Prats MD, Marigil M, Vera J, Ferrer M, Montoro M. Spectrum of gluten-sensitive enteropathy in patients with dysmotility-like dyspepsia. GASTROENTEROLOGIA Y HEPATOLOGIA 2012; 36:11-20. [PMID: 23103052 DOI: 10.1016/j.gastrohep.2012.07.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2012] [Revised: 07/17/2012] [Accepted: 07/24/2012] [Indexed: 10/27/2022]
Abstract
BACKGROUND Dysmotility-like dyspepsia symptoms are frequent in patients with gluten-sensitive enteropathy (GSE). Current data suggest that patients with mild enteropathy may be present with gluten-sensitive symptoms and complications. AIM To investigate the prevalence of GSE, including mild enteropathy, in patients with dysmotility-like dyspepsia symptoms. METHODS We retrospectively studied 142 patients who presented dysmotility-like dyspepsia symptoms and normal upper gastrointestinal endoscopy. Endoscopic duodenal biopsies were taken and processed using hematoxylin-eosin staining and CD3 immunophenotyping. In patients with enteropathy (number of intraepithelial lymphocytes greater than 25 per 100 enterocytes) we also performed coeliac serology (anti-tissue transglutaminase IgA) and HLA-DQ2/DQ8 genotyping. A gluten-free diet was offered if one of these markers was positive. The final GSE diagnosis was established based on clinical and histopathological response to the gluten-free diet after 18 months of follow-up. RESULTS Fifty-one patients (35.9%) had enteropathy; 4 (2.8%) Marsh type 3b, 24 (16.9%) Marsh type 3a, 3 (2.1%) Marsh type 2, and 20 (14.1%) Marsh type 1. A positive serology result was extremely low (6.7%) in mild enteropathy (Marsh type 1-3a) in contrast with Marsh type 3b patients (50%). Most patients with enteropathy had positive HLA DQ2 or -DQ8 genotyping (84.1%). Out of the 37 patients who started a gluten-free diet, 34 (91.9%) improved their symptoms, and 28 of 32 (87.5%) had a histopathological or serological response. A final GSE diagnosis was established in 28 of the 142 patients (19.7%). CONCLUSION Gluten-sensitive enteropathy can be a frequent and unsuspected cause of dysmotility-like dyspepsia.
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Affiliation(s)
- Santos Santolaria
- Department of Gastroenterology and Hepatology, Hospital San Jorge, Huesca, Spain.
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Lymphocytic duodenosis: aetiology and long-term response to specific treatment. Dig Liver Dis 2012; 44:643-8. [PMID: 22497904 DOI: 10.1016/j.dld.2012.03.006] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2011] [Revised: 02/29/2012] [Accepted: 03/04/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND The clinical significance of lymphocytic duodenosis remains unclear. AIM To prospectively assess the aetiology of lymphocytic duodenosis and the patterns of clinical presentation. METHODS Ninety consecutive patients with lymphocytic duodenosis and clinical symptoms of the coeliac disease spectrum were prospectively included. All subjects underwent serological testing and HLA genotyping for coeliac disease, assessment of Helicobacter pylori infection, and parasite stool examination. Intake of non-steroidal anti-inflammatory drugs was also recorded. The final aetiology of lymphocytic duodenosis was evaluated on the basis of the long-term response to specific therapy. RESULTS More than one initial potential aetiology was observed in 44% of patients. The final diagnosis was gluten-sensitive enteropathy alone or associated with Helicobacter pylori infection in 43.3%, Helicobacter pylori infection (without gluten-sensitive enteropathy) in 24.4%, non-steroidal anti-inflammatory drugs intake in 5.5%, autoimmune disease in 3.3%, and parasitic infection in 2.2%. Among first degree relatives and patients with chronic diarrhoea, the most common final diagnosis was gluten-sensitive enteropathy. In contrast, in the group presenting with chronic dyspepsia the most common diagnosis was Helicobacter pylori infection ('Diarrhoea' vs 'Dyspepsia' groups, p=0.008). CONCLUSIONS Lymphocytic duodenosis is often associated with more than one potential initial aetiology. Clinical presentation may be useful to decide the initial therapeutic approach with these patients.
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Brown AC. Gluten sensitivity: problems of an emerging condition separate from celiac disease. Expert Rev Gastroenterol Hepatol 2012; 6:43-55. [PMID: 22149581 DOI: 10.1586/egh.11.79] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Gluten sensitivity appears to be emerging as a separate condition from celiac disease, yet no clear definition or diagnosis exists. As a result, patients with gluten sensitivity experience delayed diagnosis and continuing symptoms if they consume gluten. This emerging medical problem may involve human genetics, plant genetic modifications, gluten as a food additive, environmental toxins, hormonal influences, intestinal infections and autoimmune diseases. The treatment is similar to that for celiac disease - a gluten-free diet. The use of a gluten-free diet or an elimination diet is encouraged in assisting people to determine whether or not they are gluten sensitive. It is time to not only recognize, but to treat and further research gluten sensitivity, as unconfirmed environmental factors continue to spread this problem further into the general population.
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Affiliation(s)
- Amy C Brown
- Department of Complementary and Alternative Medicine, John A Burns School of Medicine, University of Hawaii, 651 Ilalo Street, MEB 223, Honolulu, HI 96813, USA.
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Santolaria Piedrafita S, Fernández Bañares F. [Gluten-sensitive enteropathy and functional dyspepsia]. GASTROENTEROLOGIA Y HEPATOLOGIA 2011; 35:78-88. [PMID: 22177265 DOI: 10.1016/j.gastrohep.2011.10.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2011] [Accepted: 10/19/2011] [Indexed: 01/12/2023]
Abstract
Gluten-sensitive enteropathy (GSE) is increasingly diagnosed in adults. The symptoms of this disease can overlap with those of functional dyspepsia. The prevalence of GSE in dyspepsia has been reported to be 1.2-6.2% and could be higher if the entire spectrum of lesions related to gluten sensitivity, including lymphocytic enteropathy, is considered. Patients with dyspepsia secondary to GSE could be mistakenly diagnosed with functional dyspepsia unless upper gastrointestinal endoscopy is completed with duodenal biopsy and immunostaining for intraepithelial lymphocytes. A missed diagnosis could have major consequences in terms of morbidity and mortality and quality of life. Consequently, endoscopic study of patients with dyspepsia should be completed by duodenal biopsy when there are symptoms suggestive of GSE.
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Lucendo AJ, García-Manzanares Á, Arias Á, Fuentes D, Álvarez N, Pérez I, Guagnozzi D, Rodrigo L. Coeliac Disease in the 21st Century: No Longer "Kids' Stuff". Gastroenterology Res 2011; 4:268-276. [PMID: 27957027 PMCID: PMC5139865 DOI: 10.4021/gr376e] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/24/2011] [Indexed: 12/22/2022] Open
Abstract
Background We aimed to determine if Coeliac disease (CD) can be still be considered a predominantly paediatric disorder, in spite of the increased incidence of adult-onset CD reported in recent years. Methods An observational, descriptive, and retrospective study was developed at two Spanish hospitals. Data was collected and analyzed from all paediatric and adult patients newly diagnosed with CD throughout the year 2010. CD diagnoses were based on a concordant clinical history, serology, HLA-DQ compatibility, the presence of mucosal lesions in duodenal biopsies with gluten dependence of symptoms, and histological lesions. Results A total of 79 patients were diagnosed with CD throughout 2010, of which 68 (86.1%) were adults. Classic symptoms (diarrhoea and iron-deficiency anaemia) were more frequent in children (90.9%), being present in only 54.4% of adults (p = 0.02). Adult patients showed, mainly, abdominal pain, dyspepsia, and GERD-related symptoms. Villous atrophy (Marsh III) was present in 63.7% of children, but only in 19.1% of adults (p = 0.004). Positive tTGA was present in 81.8% of the children and only in 19.1% of the adults (p = 0.004). Haemoglobin levels were significantly lower in children (p = 0.025), but no differences were observed in iron and ferritin blood levels. Conclusions Our study shows that adult-onset CD was the predominant presentation in two hospitals in Spain in the year 2010. Therefore, CD can no longer be considered a predominantly paediatric disorder. Marsh I and negative tTGA titters are characteristic in most of adults. New diagnostic algorithms are needed to improve correct diagnosis of CD in adults.
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Affiliation(s)
- Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Ciudad Real, Spain
| | - Álvaro García-Manzanares
- Department of Endocrinology and Nutrition, Hospital General de Tomelloso, Tomelloso, Ciudad Real, Spain
| | - Ángel Arias
- Research Unit, Hospital General La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
| | - Dolores Fuentes
- Department of Gastroenterology. Hospital Universitario Central de Asturias. Oviedo, Spain
| | - Noemí Álvarez
- Department of Gastroenterology. Hospital Universitario Central de Asturias. Oviedo, Spain
| | - Isabel Pérez
- Department of Gastroenterology. Hospital Universitario Central de Asturias. Oviedo, Spain
| | - Danila Guagnozzi
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Ciudad Real, Spain
| | - Luis Rodrigo
- Department of Gastroenterology. Hospital Universitario Central de Asturias. Oviedo, Spain
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Abstract
At upper gastrointestinal endoscopy to investigate unexplained diarrhea and iron deficiency anemia, duodenal biopsies are often taken to exclude a diagnosis of coeliac disease. While histology remains the gold standard for this diagnosis, recent developments in serological testing may overtake this as a first line test and biopsy restricted to confirming the diagnosis. Established coeliac disease on biopsy is straightforward, but early lesions may pose a challenge. Newer endoscopic procedures such as push-pull enteroscopy (balloon enteroscopy) with biopsy allow access to the small bowel beyond the second part of the duodenum. Controversy remains as to what constitutes the normal histology of the duodenum, and small bowel. Lymphocytic duodenosis (increased intraepithelial lymphocytes with normal villous architecture) in patients with negative coeliac serology can be associated with Helicobacter pylori, drugs, autoimmune and other diseases including food allergy. Full thickness small intestinal biopsies can aid in investigation of enteric neuropathies in severe dysmotility disorders. Biopsies are also taken to investigate malabsorption due to suspected infectious and metabolic disorders. Despite highly active anti-retroviral therapy (HAART), immunosuppressed patients may be affected by duodenal pathogens. The histology of duodenal mucosa in acid related disorders reflects the damage seen at endoscopy. Although the prevalence of duodenal ulcer disease is decreasing, drugs causing ulceration remain an important disease entity. Recent observations in functional bowel disorders suggest that the duodenum may be a key site for pathology. In functional dyspepsia, patients with early satiety may have excess eosinophil infiltration, and the mast cell is probably a key player in the irritable syndrome in the small intestine.
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Dynamics of non-conventional intraepithelial lymphocytes-NK, NKT, and γδ T-in celiac disease: relationship with age, diet, and histopathology. Dig Dis Sci 2011; 56:2042-9. [PMID: 21221796 DOI: 10.1007/s10620-010-1534-5] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2010] [Accepted: 12/10/2010] [Indexed: 01/12/2023]
Abstract
BACKGROUND Intraepithelial lymphocytes (IEL) are a heterogeneous population of lymphocytes raised in celiac disease (CD), whose role in CD pathogenesis remains to be defined. AIMS To investigate how the age of diagnosis, diet, and the severity of the histological lesions are related to the changes observed in unconventional IEL populations. METHODS Prospective analysis of 101 confirmed celiac patients from a single center, including 66 at diagnosis (45 children, 21 adults) and 112 non-celiac controls (12 children, 100 adults). IEL from duodenal biopsies were studied by six-color flow cytometry. The results were analyzed in relationship with age, diet (gluten intake), and histopathology (Marsh type). RESULTS In comparison with respective age controls, both children and adult patients showed duodenal intraepithelial lymphocytosis with significant differences in every single non-conventional IEL population: CD3+ TCR γδ, NK (CD3-, CD16+, CD56+), NKT (CD3+, CD161+, CD56+), and iNKT (CD3+ Vα24) (P < 0.001 for all). Gluten intake was not only directly associated with severe atrophy, but also with decreased percentages of NK (P = 0.02), NKT (P = 0.003), and iNKT (P = 0.03). Changes in iNKT and γδ IEL were more marked in celiac children compared with celiac adults (P = 0.02 and 0.01, respectively). In contrast, increased CD3+ TCR γδ were diet- and Marsh grade-independent. CONCLUSIONS The typical phenotypical profile of intraepithelial lymphocytosis in untreated pediatric and adult celiacs consists of increased CD3+ TCR γδ populations with decreased NK, NKT, and iNKT cells. NK, NKT, and iNKT IEL, but not γδ IEL, are dynamic populations associated with diet, age, and histopathology.
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Elfström P, Granath F, Ekström Smedby K, Montgomery SM, Askling J, Ekbom A, Ludvigsson JF. Risk of lymphoproliferative malignancy in relation to small intestinal histopathology among patients with celiac disease. J Natl Cancer Inst 2011; 103:436-44. [PMID: 21289299 DOI: 10.1093/jnci/djq564] [Citation(s) in RCA: 104] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Celiac disease is associated with an increased risk of malignant lymphomas. The risk of lymphoproliferative malignancies in patients with small intestinal inflammation without villous atrophy and in patients with latent celiac disease is unknown. METHODS We performed a cohort study using duodenal and jejunal biopsy data that were collected from all 28 Swedish pathology departments (July 1969 to February 2008). We identified two population-based cohorts composed of 28,989 individuals with biopsy-verified celiac disease (villous atrophy, Marsh stage 3) and 13,140 individuals with small intestinal inflammation without villous atrophy (Marsh 1 + 2) and a regional cohort of 3711 individuals with latent celiac disease (positive celiac disease serology and normal mucosa). Cancer data were obtained by linkage to the National Cancer Registry. We used Cox regression to estimate hazard ratios (HRs) for lymphoproliferative malignancy and any solid cancer among the three cohorts compared with a total of 227,911 age- and sex-matched reference individuals. RESULTS Although biopsy-verified celiac disease and intestinal inflammation were associated with lymphoproliferative malignancy (for celiac disease, HR = 2.82; 95% confidence interval [CI] = 2.36 to 3.37, n = 193; for inflammation, HR = 1.81; 95% CI = 1.42 to 2.31, n = 89), latent celiac disease was not associated with lymphoproliferative malignancy (HR = 0.97; 95% CI = 0.44 to 2.14, n = 7). The absolute rates of lymphoproliferative malignancies among persons with celiac disease, small intestinal inflammation, and latent celiac disease were 70.3 per 100,000 person-years, 83.4 per 100,000 person-years, and 28.0 per 100,000 person-years, respectively. Compared with individuals with celiac disease, individuals with small intestinal inflammation or latent celiac disease were at a statistically significantly lower risk of lymphoproliferative malignancy. Risk of any solid cancer was not increased beyond the first year of follow-up in any cohort. Celiac disease was associated with Hodgkin lymphoma and both T-cell and B-cell non-Hodgkin lymphomas. CONCLUSION The risk of lymphoproliferative malignancy in celiac disease is dependent on small intestinal histopathology, with no increased risk in latent celiac disease.
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Affiliation(s)
- Peter Elfström
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
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18
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Abstract
Coeliac disease is increasing in prevalence, which is currently estimated at one in 100 of the population and may occur de novo in adults. The diagnosis requires a joint clinicopathological approach; the recommended first-line test is serology with immunoglobulin A (IgA) tissue transglutaminase and IgA endomysial antibodies. These serological tests show high levels of sensitivity and specificity, but biopsy is the gold standard to confirm the diagnosis. It is important that both tests are performed before the introduction of a gluten-free diet. Although the classical histopathology changes of coeliac disease with partial or total villous atrophy are well recognized, the pathology classification of coeliac disease is changing, with recognition that coeliac disease may show minimal pathology (normal architecture and an intraepithelial lymphocyte count/100 enterocytes ≥ 25). This entity is also described as lymphocytic duodenosis, and recommendation of follow-up serology testing is paramount in this condition. Follow-up of patients with coeliac disease is warranted, as normal serology does not predict mucosal recovery. Failure to heal predicts risk of progression to refractory coeliac disease and malignancies. Refractory coeliac disease occurs in 1-2% of patients and this diagnosis requires a combined clinical and histopathology approach with immunocytochemistry.
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Affiliation(s)
- Marjorie M Walker
- Department of Histopathology, Imperial College London, St. Mary's Hospital, London, UK.
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Walker MM, Murray JA, Ronkainen J, Aro P, Storskrubb T, D’Amato M, Lahr B, Talley NJ, Agreus L. Detection of celiac disease and lymphocytic enteropathy by parallel serology and histopathology in a population-based study. Gastroenterology 2010; 139:112-9. [PMID: 20398668 PMCID: PMC2902605 DOI: 10.1053/j.gastro.2010.04.007] [Citation(s) in RCA: 176] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2009] [Revised: 03/24/2010] [Accepted: 04/06/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Although serologic analysis is used in diagnosis of celiac disease, histopathology is considered most reliable. We performed a prospective study to determine the clinical, pathologic, and serologic spectrum of celiac disease in a general population (Kalixanda study). METHODS A random sample of an adult general population (n = 1000) was analyzed by upper endoscopy, duodenal biopsy, and serologic analysis of tissue transglutaminase (tTg) levels; endomysial antibody (EMA) levels were analyzed in samples that were tTg+. The cut off values for diagnosis of celiac disease were villous atrophy with 40 intraepithelial lymphocytes (IELs)/100 enterocytes (ECs). RESULTS Samples from 33 subjects were tTg+, and 16 were EMA+. Histologic analysis identified 7 of 1000 subjects (0.7%) with celiac disease; all were tTg+, and 6 of 7 were EMA+. Another 26 subjects were tTg+ (7/26 EMA+). This was addressed by a second quantitative pathology study (nested case control design) using a threshold of 25 IELS/100 ECs. In this analysis, all 13 samples that were tTg+ and EMA+ had > or =25 IELs/100 ECs. In total, 16 subjects (1.6%) had serologic and histologic evidence of gluten-sensitive enteropathy. IELs were quantified in duodenal biopsy samples from seronegative individuals (n = 500); 19 (3.8%) had >25 IELs and lymphocytic duodenosis. CONCLUSIONS Measurement of > or =25 IELs/100 ECs correlated with serologic indicators of celiac disease; a higher IEL threshold could miss 50% of cases. Quantification of tTg is a sensitive test for celiac disease; diagnosis can be confirmed by observation of > or =25 IELs/100ECs in duodenal biopsy specimens. Lymphocytic enteropathy (celiac disease and lymphocytic duodenosis) is common in the population (5.4%).
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Affiliation(s)
- Marjorie M. Walker
- Department of Histopathology, Faculty of Medicine, St. Mary’s Campus, Imperial College London, UK
| | - Joseph A. Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Jukka Ronkainen
- Center for Family and Community Medicine, Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Pertti Aro
- Center for Family and Community Medicine, Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Tom Storskrubb
- Center for Family and Community Medicine, Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Mauro D’Amato
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
| | - Brian Lahr
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Nicholas J. Talley
- Mayo Clinic College of Medicine, Jacksonville, Florida USA and Department of Medicine, University of Sydney, Sydney, Australia
| | - Lars Agreus
- Center for Family and Community Medicine, Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden
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Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet. Am J Gastroenterol 2010; 105:1412-20. [PMID: 20145607 PMCID: PMC2881171 DOI: 10.1038/ajg.2010.10] [Citation(s) in RCA: 306] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Clinical response is typically observed in most adults with celiac disease (CD) after treatment with a gluten-free diet (GFD). The rate of mucosal recovery is less certain. The aims of this study were (1) to estimate the rate of mucosal recovery after GFD in a cohort of adults with CD, and (2) to assess the clinical implications of persistent mucosal damage after GFD. METHODS The study group included adults with biopsy-proven CD evaluated at the Mayo Clinic who had duodenal biopsies at diagnosis and at least one follow-up intestinal biopsy to assess mucosal recovery after starting a GFD. The primary outcomes of interest were mucosal recovery and all-cause mortality. RESULTS Of 381 adults with biopsy-proven CD, 241 (73% women) had both a diagnostic and follow-up biopsy available for re-review. Among these 241, the Kaplan-Meier rate of confirmed mucosal recovery at 2 years following diagnosis was 34% (95% confidence interval (CI): 27-40%), and at 5 years was 66% (95% CI: 58-74%). Most patients (82%) had some clinical response to GFD, but it was not a reliable marker of mucosal recovery (P=0.7). Serological response was associated with confirmed mucosal recovery (P=0.01). Poor compliance to GFD (P<0.01), severe CD defined by diarrhea and weight loss (P<0.001), and total villous atrophy at diagnosis (P<0.001) were strongly associated with persistent mucosal damage. There was a trend toward an association between achievement of mucosal recovery and a reduced rate of all-cause mortality (hazard ratio=0.13, 95% CI: 0.02-1.06, P=0.06), adjusted for gender and age. CONCLUSIONS Mucosal recovery was absent in a substantial portion of adults with CD after treatment with a GFD. There was a borderline significant association between confirmed mucosal recovery (vs. persistent damage) and reduced mortality independent of age and gender. Systematic follow-up with intestinal biopsies may be advisable in patients diagnosed with CD as adults.
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Coeliac disease presenting with bilateral fibular stress fractures. Foot Ankle Surg 2009; 15:96-100. [PMID: 19410177 DOI: 10.1016/j.fas.2008.06.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2007] [Revised: 06/08/2008] [Accepted: 06/09/2008] [Indexed: 02/04/2023]
Abstract
We present the case of an apparently healthy 22-year-old female who presented with atraumatic stress fractures of both fibulae. Further investigation demonstrated that she had osteopoenia secondary to occult coeliac disease. The fractures were successfully treated non-operatively. The awareness of the prevalence of occult coeliac disease is increasing due to simpler diagnostic tests, as is its significance as a cause of secondary osteoporosis. Knowing the relationship between these two conditions will help orthopaedic surgeons treating such patients to refer them promptly to appropriate specialists.
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Prause C, Ritter M, Probst C, Daehnrich C, Schlumberger W, Komorowski L, Lieske R, Richter T, Hauer AC, Stern M, Uhlig HH, Laass MW, Zimmer KP, Mothes T. Antibodies against deamidated gliadin as new and accurate biomarkers of childhood coeliac disease. J Pediatr Gastroenterol Nutr 2009; 49:52-8. [PMID: 19465869 DOI: 10.1097/mpg.0b013e318195dae3] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Assays of tissue transglutaminase antibodies (anti-tTG) represent the cornerstone of serological coeliac disease (CD) diagnostics. Assays of antibodies against native gliadin (anti-nGli) lost importance due to low validity. We investigated the performance of new assays for antibodies against deamidated gliadin (anti-dGli) in childhood CD. METHODS We retrospectively compared children (142 with active CD and 160 without CD, diagnosis confirmed or excluded by intestinal biopsy) concerning (immunoglobulin [Ig] G and IgA) anti-nGli, anti-tTG, and 2 different anti-dGli assays. RESULTS IgG-anti-dGli1, IgG-anti-dGli2, and IgA-anti-tTG performed similarly. Area under the receiver-operating characteristic curve (AUC) was 98.6%, 98.9%, and 97.9%; accuracy was 94.7%, 95.7%, and 96.7%. Anti-dGli1 and anti-dGli2 (IgG and IgA) and IgA-anti-tTG performed significantly better than IgA-anti-nGli and IgG-anti-nGli. Both IgG-anti-dGli showed higher AUC and accuracy than IgA-anti-dGli and IgG-anti-tTG. Combined evaluation of IgA-anti-tTG with one of the IgG-anti-dGli tests reduced the rate of falsely classified patients. At enhanced cutoff (specificity >99%), sensitivity was above 67% for both IgG-anti-dGli and IgA-anti-tTG. If IgA-anti-tTG assay was combined with one of the IgG-anti-dGli tests, then the fraction of patients identified with more than 99% specificity as coeliacs increased significantly above 84.5%. Combined evaluation of the 2 IgG-anti-dGli tests did not improve the performance. CONCLUSIONS The new IgA and IgG-anti-dGli tests outperform conventional anti-nGli assays. The validity of IgG-anti-dGli cannot be distinguished from IgA-anti-tTG. It should be studied prospectively whether antibody assays could replace biopsy in diagnosis of CD in a substantial segment of children.
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Affiliation(s)
- Christian Prause
- Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital, Leipzig, Germany
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Fan X, Sellin JH. Review article: Small intestinal bacterial overgrowth, bile acid malabsorption and gluten intolerance as possible causes of chronic watery diarrhoea. Aliment Pharmacol Ther 2009; 29:1069-77. [PMID: 19222407 DOI: 10.1111/j.1365-2036.2009.03970.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Chronic watery diarrhoea is one of the most common symptoms prompting GI evaluation. Recently, new diagnostic considerations have emerged as possible factors in chronic diarrhoea. AIM To review available data regarding diagnosis and treatment of chronic diarrhoea with an emphasis on bacterial overgrowth and bile acid malabsorption. METHODS A systematic search of the English language literature of chronic diarrhoea was performed focused on three possible aetiologies of diarrhoea: small intestinal bacterial overgrowth (SIBO), idiopathic bile salt malabsorption (IBAM), gluten responsive enteropathy. RESULTS Recent studies suggest that SIBO and bile acid malabsorption may have been underestimated as possible causes of chronic watery diarrhoea. Gluten intolerance with negative coeliac serology is a contentious possible cause of watery diarrhoea, but requires further research before acceptance as an entity. CONCLUSION In patients with otherwise unexplained chronic watery diarrhoea, small intestinal bacterial overgrowth and bile salt malabsorption should be considered and investigated.
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Affiliation(s)
- X Fan
- Division of Gastroenterology, University of Texas Medical Branch, Galveston, TX, USA
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Abstract
Celiac disease (CD) is an autoimmune enteropathy triggered in susceptible individuals by ingestion of gliadin-containing grains. Although the autoimmune process targets mainly the intestinal mucosa, CD can manifest itself with a variety signs and symptoms affecting any organ or tissue. For many years, CD has been underdiagnosed because of poor awareness. However, studies showing a high prevalence of CD in North America, followed by a consensus conference on CD organized by the National Institutes of Health, have fueled a campaign to raise awareness among subspecialists and primary physicians. Nevertheless, guidelines for the diagnosis of CD remain poorly appreciated and many health care professionals remain confused about its proper management. This review is intended to clarify "facts and fantasies" about CD diagnosis.
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Affiliation(s)
- Carlo Catassi
- University of Maryland School of Medicine, Mucosal Biology Research Center and Center for Celiac Research, Health Science Facility II, Baltimore, MD 21201, USA
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Vivas Alegre S, Ruiz de Morales JM. Enfermedad celíaca refractaria. GASTROENTEROLOGIA Y HEPATOLOGIA 2008; 31:310-6. [DOI: 10.1157/13119885] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Arikan C, Zihni C, Cakir M, Alkanat M, Aydogdu S. Morphometric analysis of small-bowel mucosa in Turkish children with celiac disease and relationship with the clinical presentation and laboratory findings. Dig Dis Sci 2007; 52:2133-9. [PMID: 17406838 DOI: 10.1007/s10620-006-9606-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2006] [Accepted: 09/07/2006] [Indexed: 01/08/2023]
Abstract
We aimed to analyze morphometric features of the small-bowel mucosa in children with celiac disease, to assess the diagnostic limit values of morphometric findings, and to examine the association of morphometric findings with the clinical presentation and laboratory findings. The study comprised 33 patients with celiac disease and 35 pediatric patients undergoing endoscopy for other causes. Biopsy specimens were reanalyzed for (1) intraepithelial lymphocytes, (2) goblet cells, (3) villous height, and (4) villous/crypt ratio. The morphometric parameters of the patients were compared with controls. Then celiac patients were divided into two groups according to the presence of total villous atrophy and clinical and laboratory findings were compared. Histologic examination revealed that goblet cells, villus height, and villous/crypt ratio were significantly lower and intraepithelial lymphocytes were significantly higher in celiac patients. Cutoff values for intraepithelial lymphocytes and goblet cells in celiac patients were 31/100 and 7.8/100 epithelial cells, respectively. Moreover, for villus height and villous/crypt ratio, cutoff values were 633 microm and 0.72, respectively. Serum folic acid and vitamin B(12) levels were significantly lower in patients with total villous atrophy and were positively correlated with the severity of villous atrophy. We suggest that morphologic examination and laboratory data are important for definitive diagnosis. Villous/crypt ratio is the most sensitive and specific parameter, and intraepithelial lymphocytes may be used along with villous/crypt ratio, especially in the early phase. Folic acid and vitamin B(12) levels are good indicators of villous atrophy.
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Affiliation(s)
- Cigdem Arikan
- Department Pediatric Gastroenterology, Hepatology, and Nutrition, Faculty of Medicine, Ege University, Izmir, Turkey.
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Remes-Troche JM, Adames K, Castillo-Rodal AI, Ramírez T, Barreto-Zuñiga R, López-Vidal Y, Uscanga LF. Intraepithelial gammadelta+ lymphocytes: a comparative study between celiac disease, small intestinal bacterial overgrowth, and irritable bowel syndrome. J Clin Gastroenterol 2007; 41:671-6. [PMID: 17667051 DOI: 10.1097/01.mcg.0000247994.34957.ae] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND Intraepithelial lymphocytes (IELs) phenotyping has emerged as a useful test in intestinal pathology. In celiac disease (CD), a permanent and marked increase of gammadelta+ IELs has been described. However, there is a lack of knowledge about this peculiar IELs population in other intestinal pathologies. AIM To analyze the percentage of IELs, specifically gammadelta+ IELs subset, present in duodenal mucosa biopsies from patients with CD and compare it with those obtained from patients with small intestinal bacterial overgrowth (SIBO) or irritable bowel syndrome (IBS). METHODS Twelve patients with untreated CD, 8 patients with SIBO, and 10 patients with diarrhea-predominant IBS were evaluated. All subjects underwent upper endoscopy for mucosal biopsy and jejunal aspirate. From 2 small bowel biopsies, intraepithelial cells were isolated and labeled with the following monoclonal antibodies CD103-PE (phycoerythrin), CD3-FITC (fluoresecein isothio-cynate), CD-7R-PE, CD45RO-APC (allophycocyanin), and TcR gammadelta-FITC. Flow cytometry analysis was performed on a standard FACScan. Total and IELs subset counts were expressed as percentage. RESULTS Mean total IELs percentage was 16.7+/-6% in IBS, 25.4+/-17% in SIBO, and 26+/-13% in CD patients (P=0.2). CD and SIBO patients, had significantly higher percentages of gammadelta+ IELs (15.7+/-13% and 14.6+/-8%) than IBS subjects (4.1+/-2.5%, P<0.05). There was no difference between CD and SIBO (P=0.6). CONCLUSIONS An increased density of gammadelta+ IELs is typical, but not specific for CD. A similar increase was observed in subjects with SIBO. Our findings suggest that this unique T-cell population might have a key role against intestinal bacterial infections.
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Affiliation(s)
- José Maria Remes-Troche
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Facultad de Medicina, UNAM, Mexico City, Mexico.
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Abstract
Coeliac disease is the manifestation of an immune hypersensitivity reaction towards gluten and related proteins, in genetically predisposed people. Although the precise pathogenesis of this condition remains to be fully elucidated, it is probably multifactorial in origin. The diagnosis of coeliac disease has traditionally depended on intestinal biopsies alone; nowadays, the diagnosis has been expanded to include an array of serological markers. This review is intended to offer pathologists an update of the relevant history and immunopathology pertaining to coeliac disease and also to offer recommendations on the ongoing responsibilities of the pathologist in the diagnosis and reporting of coeliac disease.
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Affiliation(s)
- B C Dickson
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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