|
1
|
Donnelly SC. Extensive Mucosal Disease: Coeliac Disease and Eosinophilic Enteritis. INTESTINAL FAILURE 2023:161-175. [DOI: 10.1007/978-3-031-22265-8_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
2
|
Newnham ED, Clayton-Chubb D, Nagarethinam M, Hosking P, Gibson PR. Randomised clinical trial: adjunctive induction therapy with oral effervescent budesonide in newly diagnosed coeliac disease. Aliment Pharmacol Ther 2021; 54:419-428. [PMID: 34181750 DOI: 10.1111/apt.16446] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 04/15/2021] [Accepted: 05/11/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND The healing of the mucosal lesion in patients with coeliac disease is slow. AIM To determine whether concurrent budesonide and gluten-free diet hasten small bowel healing and symptomatic improvement in patients with newly diagnosed coeliac disease. METHODS In a pilot, randomised, double-blind trial, effects on Marsh grading and quantitative duodenal morphometry of 10 weeks' effervescent budesonide (initially 9 mg/day) or placebo were assessed after 8 and 52 weeks. Multiple clinical measures and adverse events were assessed. RESULTS Nineteen patients were randomised to budesonide and 18 to placebo. No differences (all P > 0.32) were observed for the week-8 mucosal response (Marsh 0 or 1) (budesonide: 37% vs placebo: 28%), week-8 remission (Marsh 0) (32% vs 17%), week-52 response (63% vs 44%) and week-52 remission (42% vs 33%). Likewise, the improvement from baseline in villous-height : crypt-depth ratio was not different for the treatment groups. There were no statistically significant differences in clinical measures or adverse events between the treatment groups. No corticosteroid adverse effects were observed. In a post hoc analysis of all patients, Marsh 3C was present at the diagnostic biopsy in 1/9 achieving mucosal remission at 8 weeks versus 18/23 not (P < 0.001) and mean villous-height : crypt-depth ratio was 1.06 (SD: 0.73) versus 0.46 (0.38) (P = 0.005). CONCLUSIONS In this pilot trial, induction therapy with budesonide had no significant effect on mucosal healing in patients with coeliac disease concurrently initiated on a gluten-free diet. Mucosal remission at 8 weeks occurred in approximately one in four patients and was associated with less severe histological lesions at diagnosis.
Collapse
Affiliation(s)
- Evan D Newnham
- Departments of Gastroenterology and Hepatology, Eastern Health, Melbourne, Vic., Australia
| | - Daniel Clayton-Chubb
- Departments of Gastroenterology and Hepatology, Eastern Health, Melbourne, Vic., Australia
| | - Meena Nagarethinam
- Departments of Gastroenterology and Hepatology, Eastern Health, Melbourne, Vic., Australia
| | | | - Peter R Gibson
- Departments of Gastroenterology and Hepatology, Eastern Health, Melbourne, Vic., Australia.,Department of Gastroenterology, Alfred Health, Melbourne, Vic., Australia
| |
Collapse
|
|
3
|
Sethi A, Helfand A, Balikani L, Bunker M, Finley G. Association of Celiac Disease With Pembrolizumab. Cureus 2021; 13:e15565. [PMID: 34277188 PMCID: PMC8272441 DOI: 10.7759/cureus.15565] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2021] [Indexed: 12/19/2022] Open
Abstract
Immune checkpoint inhibitors (ICIs) in the recent times have transformed the landscape of the management of many solid tumors. Unfortunately, many immune-related adverse effects are associated with ICIs, which lead to a negative outcome in cancer treatment. We present a case of a 63-year-old female with metastatic adenocarcinoma of unknown origin, who developed celiac disease during the course of treatment with pembrolizumab. Association of celiac disease with this form of immunotherapy has never been documented before.
Collapse
Affiliation(s)
- Ashish Sethi
- Medical Oncology, Allegheny Health Network, Pittsburgh, USA
| | | | - Lame Balikani
- Pathology, Allegheny Health Network, Pittsburgh, USA
| | - Mark Bunker
- Pathology, Allegheny Health Network, Pittsburgh, USA
| | - Gene Finley
- Hematology & Oncology, Allegheny Health Network, Pittsburgh, USA
| |
Collapse
|
|
4
|
Tan IL, Withoff S, Kolkman JJ, Wijmenga C, Weersma RK, Visschedijk MC. Non-classical clinical presentation at diagnosis by male celiac disease patients of older age. Eur J Intern Med 2021; 83:28-33. [PMID: 33218785 DOI: 10.1016/j.ejim.2020.09.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 09/21/2020] [Accepted: 09/21/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND . In a biopsy-proven adult celiac disease (CeD) cohort from the Netherlands, male patients were diagnosed with CeD at significantly older ages than female patients. OBJECTIVES To identify which factors contribute to diagnosis later in life and whether diagnostic delay influences improvement of symptoms after starting a gluten-free diet (GFD). METHODS . We performed a questionnaire study in 211 CeD patients (67:144, male:female) with median age at diagnosis of 41.8 years (interquartile range: 25-58) and at least Marsh 2 histology. RESULTS . Classical symptoms (diarrhea, fatigue, abdominal pain and/or weight loss) were more frequent in women than men, but sex was not significantly associated with age at diagnosis. In a multivariate analysis, a non-classical presentation (without any classical symptoms) and a negative family history of CeD were significant predictors of older age at diagnosis (coefficients of 8 and 12 years, respectively). A delay of >3 years between first symptom and diagnosis was associated with slower improvement of symptoms after start of GFD, but not with sex, presentation of classical symptoms or age at diagnosis. CONCLUSION . Non-classical CeD presentation is more prevalent in men and is associated with a diagnosis of CeD later in life. Recognizing CeD sooner after onset of symptoms is important because a long diagnostic delay is associated with a slower improvement of symptoms after starting a GFD.
Collapse
Affiliation(s)
- Ineke L Tan
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Sebo Withoff
- Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Jeroen J Kolkman
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, 7500 KA Enschede, the Netherlands
| | - Cisca Wijmenga
- Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands
| | - Marijn C Visschedijk
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, Groningen, the Netherlands.
| |
Collapse
|
|
5
|
Levinta A, Mukovozov I, Tsoutsoulas C. Use of a Gluten-Free Diet in Schizophrenia: A Systematic Review. Adv Nutr 2018; 9:824-832. [PMID: 30325398 PMCID: PMC6247287 DOI: 10.1093/advances/nmy056] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
We performed a systematic review of the literature to determine whether adherence to a gluten-free diet (GFD) leads to improved outcomes for patients with schizophrenia. We searched the AMED (Allied and Complementary Medicine; 1985-June 2016), MEDLINE (1946-June 2016), and Embase (1980-2016 week 24) databases using the terms "wheat" or "glutenin" or "gliadin" or "gluten" AND "schizophrenia." A total of 9 studies met the inclusion criteria for this review: 1 randomized controlled trial, 7 crossover studies, and 1 open-label pilot study. Six of the included studies demonstrated beneficial effects including improved functioning and decreased symptom severity after the course of a GFD, whereas 3 studies found no benefits. All of the included studies found that a GFD is well tolerated and can be adhered to by patients with schizophrenia. The findings of this systematic review should be interpreted with caution due to limitations inherent to nonrandomized trials, as well as the heterogeneity in the study design and the length of the GFD applied in each study. Publication bias is another potential limitation. Further research is required to examine the biomarkers of gluten sensitivity and inflammation to effectively target those patients with schizophrenia who will benefit most from this dietary intervention.
Collapse
Affiliation(s)
- Anastasia Levinta
- Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Ilya Mukovozov
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | | |
Collapse
|
|
6
|
Can High Titres of Anti Tissue Transglutaminase Antibodies Reduce the Need for Intestinal Biopsy for Diagnosis of Celiac Disease? Indian J Clin Biochem 2018; 33:456-460. [PMID: 30319193 DOI: 10.1007/s12291-017-0695-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Accepted: 09/07/2017] [Indexed: 01/15/2023]
Abstract
Traditionally small intestinal biopsy has been considered a gold standard for the diagnosis of celiac disease (CD). But now data has shown that serological markers like anti-tissue-transglutaminase antibodies (tTGA) can be used to make the diagnosis with great sensitivity and specificity. The objective of the present study was to evaluate whether patients with high probability of CD and high titre of tTGA, have a high probability of intestinal damage and may not require biopsy for final diagnosis. All the cases with tTGA levels ≥15 IU/ml and who subsequently underwent biopsy from July 2010 to June 2013 were selected. Histopathological findings graded as per Marsh classification were correlated with serum tTGA levels. Grade 3 lesions were considered diagnostic for the disease. Out of total 731 patients 470 had serum tTGA levels >100 IU/ml and 261 patients had <100 IU/ml. Highest levels of tTGA (219.3 IU/ml) were seen in grade 3c which was >12 times the normal cutoff value. Mean serum tTGA in higher histological grade i.e. 3 (3a, 3b, 3c) was 186.7 IU/ml (>12 times the normal cut off value) as compared to grade 1 which was 108.9 IU/ml (>7 times the normal cut off value). Using a tTGA cutoff value of 70 IU/ml, sensitivity was found to be 83.9% while specificity was 56.10% with an overall accuracy of 77.7%. This study confirms that a small intestinal biopsy is not always necessary for the diagnosis of CD in symptomatic patients with high tTGA levels (>70 IU/ml).
Collapse
|
|
7
|
Al-Bawardy B, Codipilly DC, Rubio-Tapia A, Bruining DH, Hansel SL, Murray JA. Celiac disease: a clinical review. Abdom Radiol (NY) 2017; 42:351-360. [PMID: 28078381 DOI: 10.1007/s00261-016-1034-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Celiac disease (CD) is an immune-mediated inflammatory enteropathy triggered by gluten exposure in genetically susceptible individuals. It has a high prevalence approaching 1% of the US population. A high index of suspicion is warranted to diagnose CD as frequently patients present with extraintestinal or atypical manifestations. CD is diagnosed by a combination of serum serologies and duodenal biopsies. The majority of patients will respond to a lifelong gluten-free diet which is the cornerstone of therapy. Complications such as refractory CD, ulcerative jejunoileitis, enteropathy associated T-cell lymphoma and small bowel adenocarcinoma occur in a minority of patients.
Collapse
Affiliation(s)
- Badr Al-Bawardy
- Division of Gastroenterology & Hepatology, Mayo Clinic, 200 First Street, S.W., Rochester, MN, 55905, USA.
| | | | - Alberto Rubio-Tapia
- Division of Gastroenterology & Hepatology, Mayo Clinic, 200 First Street, S.W., Rochester, MN, 55905, USA
| | - David H Bruining
- Division of Gastroenterology & Hepatology, Mayo Clinic, 200 First Street, S.W., Rochester, MN, 55905, USA
| | - Stephanie L Hansel
- Division of Gastroenterology & Hepatology, Mayo Clinic, 200 First Street, S.W., Rochester, MN, 55905, USA
| | - Joseph A Murray
- Division of Gastroenterology & Hepatology, Mayo Clinic, 200 First Street, S.W., Rochester, MN, 55905, USA
| |
Collapse
|
|
8
|
Frequency and Cause of Persistent Symptoms in Celiac Disease Patients on a Long-term Gluten-free Diet. J Clin Gastroenterol 2016; 50:239-43. [PMID: 26280705 DOI: 10.1097/mcg.0000000000000392] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
GOALS To estimate the frequency and cause of nonresponsive celiac disease (CD). BACKGROUND Treatment of CD is based on life-long adherence to a gluten-free diet (GFD). Some celiac patients experience persistence of symptoms despite a GFD. This condition is defined as nonresponsive CD. STUDY Celiac patients on a GFD for at least 12 months underwent diet compliance assessment, laboratory tests, breath tests, endoscopic, and histologic evaluations according to the symptoms/signs reported. RESULTS Seventy of 321 (21.8%) patients had persistent or recurrent symptoms/signs. The cause of symptom persistence was evaluated in 56 of 70 patients. Thirteen of 56 (23%) patients were antiendomysial antibody positive. Among the patients with negative serology, 1 had fibromyalgia, and 3 had evidence that disproved the diagnosis of CD. The remaining 39 patients with negative serology underwent duodenal biopsy sampling, which evidenced histologic alterations in 24 patients. Among the 15 patients with normal histology 3 were lactose intolerant, 9 had irritable bowel syndrome, 2 had gastroesophageal reflux disease, and in 1 patient a cause for the persistent symptom was not identified. In patients with confirmed diagnosis of CD, exposure to dietary gluten was the main cause of persistence of symptoms/signs, and consistently after dietary modification, symptoms resolved in 63% of the patients at later time points during follow-up. CONCLUSION Nonresponsive CD occurs in nearly one fifth of celiac patients on GFD and its occurrence suggests further investigations to optimize the management of celiac patients.
Collapse
|
|
9
|
Dewar DH, Donnelly SC, McLaughlin SD, Johnson MW, Ellis HJ, Ciclitira PJ. Celiac disease: Management of persistent symptoms in patients on a gluten-free diet. World J Gastroenterol 2012; 18:1348-56. [PMID: 22493548 PMCID: PMC3319961 DOI: 10.3748/wjg.v18.i12.1348] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2010] [Revised: 09/22/2011] [Accepted: 01/22/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate all patients referred to our center with non-responsive celiac disease (NRCD), to establish a cause for their continued symptoms.
METHODS: We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period. These individuals were investigated to establish the eitiology of their continued symptoms. The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement. They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion. A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible. Colonoscopy, lactulose hydrogen breath testing, pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted. Their clinical progress was followed over a minimum of 2 years.
RESULTS: One hundred and twelve consecutive patients were referred with NRCD. Twelve were found not to have celiac disease (CD). Of the remaining 100 patients, 45% were not adequately adhering to a strict gluten-free diet, with 24 (53%) found to be inadvertently ingesting gluten, and 21 (47%) admitting non-compliance. Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%. Refractory CD was diagnosed in 9%. Three of these were diagnosed with intestinal lymphoma. After 2 years, 78 patients remained well, eight had continuing symptoms, and four had died.
CONCLUSION: In individuals with NRCD, a remediable cause can be found in 90%: with continued gluten ingestion as the leading cause. We propose an algorithm for investigation.
Collapse
|
|
10
|
Abstract
Malabsorption syndrome encompasses numerous clinical entities that result in chronic diarrhea, abdominal distention, and failure to thrive. These disorders may be congenital or acquired and include cystic fibrosis and Shwachman-Diamond syndrome; the rare congenital lactase deficiency; glucose-galactose malabsorption; sucrase-isomaltase deficiency; adult-type hypolactasia leading to acquired lactose intolerance. The pathology may be due to impairment in absorption or digestion of nutrients resulting in Nutritional deficiency, gastrointestinal symptoms, and extra gastrointestinal symptoms. Treatment is aimed at correcting the deficiencies and symptoms to improve quality of life. Common disorders of malabsorption celiac disease, pernicious anemia, and lactase deficiency are discussed in this article.
Collapse
Affiliation(s)
- Zafreen Siddiqui
- Department of Family and Community Medicine, University of Texas Southwestern Medical Center, 5909 Harry Hines Boulevard, Suite 100, Dallas, TX 75390-9067, USA.
| | | |
Collapse
|
|
11
|
Pallais JC, Mackool BT, Pitman MB. Case records of the Massachusetts General Hospital: Case 7-2011: a 52-year-old man with upper respiratory symptoms and low oxygen saturation levels. N Engl J Med 2011; 364:957-66. [PMID: 21388314 DOI: 10.1056/nejmcpc1013923] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- J Carl Pallais
- Endocrinology Division, the Department of Medicine, Massachusetts General Hospital, Boston, USA
| | | | | |
Collapse
|
|
12
|
Carroccio A, Catalano T, Fiorino M, Bongiovì A, Napoli G, Di Prima L, Ambrosiano G, Pace M, Scaturro A, Di Fede G. Collagenous colitis presenting with bloody diarrhea and rectal erosions in a patient with celiac disease: a case report. ITALIAN JOURNAL OF MEDICINE 2010. [DOI: 10.1016/j.itjm.2010.03.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
|
|
13
|
Richir M, Songun I, Wientjes C, Snel P, Dwars B. Small Bowel Adenocarcinoma in a Patient with Coeliac Disease: Case Report and Review of the Literature. Case Rep Gastroenterol 2010; 4:416-420. [PMID: 21060711 PMCID: PMC2975010 DOI: 10.1159/000313547] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Coeliac disease (CD) is an autoimmune disorder which leads to chronic inflammation of the gut. Furthermore, CD is associated with upper gastrointestinal malignancies, particularly lymphoma of the small intestine. Besides lymphoma, an increased frequency of associated small bowel carcinoma has been described. Here we report the case of a 70-year-old male suffering from CD who was treated with a gluten-free diet presenting with complaints of nausea, vomiting and weight loss of about 8 kg in two months. He underwent esophagogastroduodenoscopy, which identified distention of the stomach and duodenum and in the pars horizontalis a distinct obstruction was suggestive. However, histopathological examination showed a normal mucosal membrane. Additionally, a computed tomography scan of the abdomen was performed which showed an expanded stomach and duodenum up to the ligament of Treitz. During an explorative laparotomy a small tumor was palpated near the ligament of Treitz. Subsequently, a duodenal segment resection was performed. After surgery, the patient recovered well and left our hospital in good condition.
Collapse
Affiliation(s)
- Milan Richir
- Department of Surgery, Slotervaart Hospital, Amsterdam, The Netherlands
| | | | | | | | | |
Collapse
|
|
14
|
Prasad Shanbhogue AK, Prasad SR, Jagirdar J, Takahashi N, Sandrasegaran K, Fazzio RT, Fidler JL. Comprehensive Update on Select Immune-Mediated Gastroenterocolitis Syndromes: Implications for Diagnosis and Management. Radiographics 2010; 30:1465-87. [DOI: 10.1148/rg.306105520] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
|
|
15
|
Kohler S, Wass JAH. Hypoparathyroidism and coeliac disease: a potentially dangerous combination. J R Soc Med 2009; 102:311-4. [PMID: 19679732 DOI: 10.1258/jrsm.2009.080401] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Affiliation(s)
- Sibylle Kohler
- Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Headington, Oxford OX3 7LJ, UK
| | | |
Collapse
|
|
16
|
Rondonotti E, Villa F, Saladino V, de Franchis R. Enteroscopy in the diagnosis and management of celiac disease. Gastrointest Endosc Clin N Am 2009; 19:445-60. [PMID: 19647651 DOI: 10.1016/j.giec.2009.04.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Esophagogastroduodenoscopy (EGD) with 3 to 6 biopsies in the descending duodenum is the gold standard for the diagnosis of celiac disease. At the time of the first diagnosis of celiac disease, an extensive evaluation of the small bowel is not recommended. However, video capsule endoscopy, because of its good sensitivity and specificity in recognizing the Endoscopic features of celiac disease, can be considered a valid alternative to EGD in patients unable or unwilling to undergo EGD with biopsies. Capsule endoscopy is also a possible option in selected cases with strong suspicion of celiac disease but negative first-line tests. In evaluating patients with refractory or complicated celiac disease, in whom a complete evaluation of the small bowel is mandatory (at least in refractory celiac disease type II patients) because of the possible presence of complications beyond the reach of conventional endoscopes, both capsule endoscopy and balloon-assisted enteroscopy have been found to be helpful. In these patients, capsule endoscopy offers several advantages: it is well tolerated, it allows inspection of the entire small bowel, and it is able to recognize subtle mucosal changes. However, in this setting, capsule endoscopy should ideally be coupled with imaging techniques that provide important information about the thickness of the wall of the intestine and about extraluminal abnormalities. Although deep enteroscopy (such as balloon enteroscopy) is expensive, time-consuming, and potentially risky in these frail patients, they may have a key role, because they make it possible to take tissue samples from deep in the small intestine.
Collapse
Affiliation(s)
- Emanuele Rondonotti
- Department of Medical Sciences, Gastroenterology 3 Unit, University of Milan, IRCCS Policlinico, Mangiagalli, Regina Elena Foundation, 20122 Milan, Italy.
| | | | | | | |
Collapse
|
|
17
|
Symposium 1: Joint BAPEN and British Society of Gastroenterology Symposium on ‘Coeliac disease: basics and controversies’ Coeliac disease: optimising the management of patients with persisting symptoms? Proc Nutr Soc 2009; 68:242-8. [DOI: 10.1017/s0029665109001360] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The vast majority of patients with coeliac disease will derive benefit from a gluten-free diet. However, some patients will not improve on the gluten-free diet or they will have a relapse of their symptoms. The present review will focus on this group of patients. Definitions for non-responsive coeliac disease and refractory coeliac disease will be provided. The most common reason for recurrent symptoms is continued gluten exposure. Other causes of persisting symptoms are discussed, including alternative causes of villous atrophy or co-existent pathology. Current literature is reviewed, including an initial investigation strategy for patients with persisting symptoms. A pragmatic management plan is described that can be initiated by any clinician. Finally, the current optimal investigational pathway for patients with refractory (or suspected refractory) coeliac disease is discussed and the reported effects of a number of therapeutic options are summarised. The aim of the present article is to provide clinicians with an up-to-date review of the literature in this clinical field and allow them to determine the most appropriate management strategy.
Collapse
|
|
18
|
A blinded pilot comparison of capsule endoscopy and small bowel histology in unresponsive celiac disease. Dig Dis Sci 2009; 54:1280-3. [PMID: 18975089 DOI: 10.1007/s10620-008-0486-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2007] [Accepted: 08/06/2008] [Indexed: 12/11/2022]
Abstract
This study compares video capsule endoscopy (VCE) with histological specimens of proximal small bowel in patients with celiac disease who have failed to respond to a gluten-free diet. Patients with nonresponsive celiac disease underwent capsule endoscopy, and concordance between endoscopy and histology was then calculated using the kappa statistic. In 19 patients, endoscopy videos were reported as normal in ten (53%) case, as having mild changes in three (16%) cases, and as having moderate-severe changes in six (31%) cases. Two (11%) had acute ulcers. No small bowel tumors were seen. Endoscopy demonstrated concordance with histological changes in 14 of the 18 patients with histology available (78% concordance). The kappa statistic suggested a substantial degree of concordance between histology and endoscopic findings. Endoscopy with distal duodenal biopsies is superior to VCE in detecting proximal, nonresponsive celiac disease, but more distal lesions may be missed such that the strength of VCE lies in its ability to visualize the entire small bowel.
Collapse
|
|
19
|
Riis P. Glucocorticoids in gastro-enterology. ACTA MEDICA SCANDINAVICA. SUPPLEMENTUM 2009; 500:55-60. [PMID: 4915716 DOI: 10.1111/j.0954-6820.1969.tb16724.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
|
|
20
|
Affiliation(s)
- I Nion-Larmurier
- Service de Gastroentérologie et Nutrition, Hôpital St-Antoine, Université Pierre-et-Marie-Curie Paris-6, 75571 Paris cedex 12, France
| | | |
Collapse
|
|
21
|
Abdallah H, Leffler D, Dennis M, Kelly CP. Refractory celiac disease. Curr Gastroenterol Rep 2008; 9:401-5. [PMID: 17991341 DOI: 10.1007/s11894-007-0049-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Celiac disease (CD) is a small intestinal inflammatory disorder characterized by an immune-mediated enteropathy triggered by the ingestion of wheat gluten or related rye and barley proteins in genetically predisposed individuals carrying the human leukocyte antigens (HLA)-DQ2 or -DQ8. Nonresponsive CD (NRCD) is a clinical diagnosis defined by the persistence of signs, symptoms, and/or laboratory abnormalities typical of CD despite adherence to a gluten-free diet for at least 6 months. One cause for NRCD is refractory CD (RCD), defined as the persistence of severe villous atrophy on small intestinal biopsy despite strict gluten withdrawal for at least 6 months with no evidence of other pathology. Although rare, RCD should be suspected in individuals with an established diagnosis of CD who fail to respond primarily or secondarily to a strict gluten-free diet, particularly if they manifest significant weight loss. A thorough evaluation must be performed to distinguish RCD from other causes of NRCD. RCD may be categorized into type I or type II. Type I RCD has a more favorable prognosis compared with type II and can often be managed with nutritional supplementation and possibly low level immunosuppressive therapy. Type II RCD carries a poor prognosis and is more likely to progress to life-threatening malnutrition or intestinal T-cell lymphoma. Immunosuppressive agents and, more recently, autologous stem cell transplant have been used to treat type II RCD.
Collapse
Affiliation(s)
- Hani Abdallah
- The Celiac Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
| | | | | | | |
Collapse
|
|
22
|
Abstract
Although there is a great deal of information on celiac disease and associated involvement of other non-intestinal sites, data on concomitant changes in the structure and function of the pancreas is limited. The present review critically examines pancreatic endocrine changes that have been well documented in the literature, including insulin-dependent diabetes mellitus. Pancreatic exocrine alterations may also occur, and if severe, marked malnutrition with pancreatic failure and ductal calcification have been observed. Finally, other pancreatic disorders have been recorded with celiac disease.
Collapse
|
|
23
|
Abstract
OBJECTIVE Corticosteroids are used in patients with refractory celiac disease. In order to minimize their systemic side effects, we assessed the role of a locally active sustained release corticosteroid with minimal systemic bioavailability in patients with refractory celiac disease in an open labeled noncontrolled study. METHODS Patients who received budesonide for refractory celiac disease were classified according to whether they were primarily or secondarily unresponsive to the diet, and whether they had a polyclonal (type I) or clonal (type II) expansion of intraepithelial lymphocytes. The response to budesonide was assessed globally and by reduction in bowel movements. RESULTS Patients (N = 29, 72% female) received budesonide for a mean of 6.7 +/- 8.5 months, 5 patients (18%) had type II disease (clonal T-cell population); 76% responded to the medication, 55% completely. Response occurred when budesonide was used alone or with oral corticosteroids and/or azathioprine. There was an objective improvement in the number of bowel movements in those that responded. Response occurred in those with either primary or secondary refractory disease and in those with type II disease, irrespective of the presence of microscopic colitis (N = 7). There was no improvement in the duodenal biopsy over the study period and there were no side effects of budesonide. CONCLUSIONS Budesonide may be of value in the management of refractory celiac disease.
Collapse
Affiliation(s)
- Pardeep Brar
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA
| | | | | | | | | | | |
Collapse
|
|
24
|
Gill BM, Leffler DA. Celiac disease: diagnosis, autoimmune mechanisms and treatment. Expert Rev Clin Immunol 2007; 3:763-72. [PMID: 20477026 DOI: 10.1586/1744666x.3.5.763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Celiac disease is a systemic autoimmune disorder triggered by the ingestion of gluten found in wheat and related grains. Once considered rare, celiac disease is now thought to affect more than one in 100 individuals, and is commonly associated with other autoimmune disorders. It predisposes patients to an increased risk of malignancy if left untreated. Celiac disease is HLA restricted as only HLA-DQ2 and -DQ8 are able to bind deamidated gluten with sufficient affinity to trigger an immune response. Both cellular and humoral immune activation occur, leading to local tissue damage and antibody formation. These antibodies, primarily to tissue transglutaminase, are the basis for highly accurate serologic testing, although the gold standard for celiac disease diagnosis remains small intestinal biopsy. Currently, the only treatment for celiac disease is a life-long gluten-free diet, although multiple novel therapeutic modalities are being studied. Although most individuals with celiac disease respond completely to gluten withdrawal, 10-20% have persistent symptoms at some point during their course and less than 1% develop refractory celiac disease, an entity of substantial morbidity.
Collapse
Affiliation(s)
- Brian M Gill
- Beth Israel Deaconess Medical Center, Dana 501330, Brookline Ave, Boston, MA 02130, USA.
| | | |
Collapse
|
|
25
|
Sussman DA, Barkin J, Barkin JS. Diet resistant celiac disease. Am J Gastroenterol 2007; 102:1833-4. [PMID: 17521399 DOI: 10.1111/j.1572-0241.2007.01334.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
|
|
26
|
Kaukinen K, Peräaho M, Lindfors K, Partanen J, Woolley N, Pikkarainen P, Karvonen AL, Laasanen T, Sievänen H, Mäki M, Collin P. Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease. Aliment Pharmacol Ther 2007; 25:1237-45. [PMID: 17451570 DOI: 10.1111/j.1365-2036.2007.03311.x] [Citation(s) in RCA: 110] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Refractory sprue with malabsorption carries a risk of lymphoma. AIM To examine whether a good clinical but poor histological response during a strict gluten-free diet predicts a poor outcome. METHODS The study involved all coeliac patients who showed no histological recovery within 2 years on a strict gluten-free diet. Small intestinal biopsy and bone mineral density were investigated in 2001 and clinical features were followed up until 2005. The results were compared to those in 18 coeliac patients with a good histological recovery. RESULTS Thirteen coeliac patients had persistent small intestinal villous atrophy despite maintaining gluten-free diet. All had demonstrated a good clinical response. Osteoporosis was found in 58% and 22% of the non-responders and responders, respectively (P = 0.04). In 2005, two of the non-responders had developed symptomatic refractory sprue, one died of lymphoma and one of carcinoid tumour, and one gastric adenocarcinoma was operated. None of the 18 controls had developed refractory sprue or malignancy. The frequency of histological non-responsive disease was 1.9%. CONCLUSIONS Persistent villous atrophy in adult coeliac disease, even in the absence of symptoms, carries a risk of subsequent severe complications. The follow-up biopsy is important in detecting these individuals.
Collapse
Affiliation(s)
- K Kaukinen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
27
|
Donaldson MR, Firth SD, Wimpee H, Leiferman KM, Zone JJ, Horsley W, O'Gorman MA, Jackson WD, Neuhausen SL, Hull CM, Book LS. Correlation of duodenal histology with tissue transglutaminase and endomysial antibody levels in pediatric celiac disease. Clin Gastroenterol Hepatol 2007; 5:567-73. [PMID: 17428743 DOI: 10.1016/j.cgh.2007.01.003] [Citation(s) in RCA: 90] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS IgA antibodies against tissue transglutaminase (TTGA) and endomysium (EMA) are sensitive and specific markers for celiac disease (CD). Data correlating TTGA and EMA levels with degree of villous atrophy are limited. We compared duodenal histopathology in pediatric CD patients with TTGA and EMA serologies, symptoms, height, and weight. METHODS We identified 117 pediatric patients retrospectively who had serologic testing for IgA TTGA and IgA EMA and duodenal biopsies graded by modified Marsh criteria as 0-3c. Data were analyzed with Spearman rank correlation and multinomial logistic regression. RESULTS IgA TTGA (r = .704, P < .001) and IgA EMA (r = 0.740, P < .001) correlated with intestinal villous atrophy in pediatric CD patients by Spearman rank correlation. Similar correlations were found in a subset of 23 patients younger than 3 years of age. Multinomial logistic regression revealed increased probability of Marsh 3a or greater changes with increasing TTGA or EMA levels. Strongly positive antibody levels (TTGA >100 units or EMA titer >1:1280) were highly specific (>98%) for Marsh 3a or greater lesions. Among symptoms, abdominal distention and diarrhea were associated with abnormal histology. CONCLUSIONS IgA TTGA and EMA levels correlate with duodenal villous atrophy in pediatric CD patients. IgA TTGA >100 or EMA >1:1280 were nearly always associated with CD histopathology. With further validation of this observation, strongly positive titers might be considered sufficient for diagnosis of pediatric patients at risk for CD. Symptoms, height, and weight are not reliable predictors of CD.
Collapse
|
|
28
|
Kwon JH, Farrell RJ. Recent advances in the understanding of celiac disease: therapeutic implications for the management of pediatric patients. Paediatr Drugs 2007; 8:375-88. [PMID: 17154644 DOI: 10.2165/00148581-200608060-00005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Celiac disease (CD) is an autoimmune condition occurring in genetically susceptible individuals characterized by inflammatory injury to the mucosa of the small intestine after the ingestion of wheat glutens or related barley and rye products. Originally thought to be highly prevalent only in Northern European populations, growing evidence indicates a much higher prevalence in many other regions, including the US as well as South America, North Africa, and Asia. The growing awareness that pediatric patients may present with quite diverse and protean manifestations and the significant impact of CD on childhood development has prompted efforts to increase CD awareness for the early diagnosis and treatment of this disease. The current diagnostic criteria for CD requires characteristic histologic findings in small bowel biopsies and clinical remission when placed on a gluten-free diet. Serologic testing for CD can provide additional support for the diagnosis of CD or a means to assess efficacy and adherence to a gluten-free diet. The mainstay of treatment remains the institution of a gluten-free diet. However, patients with refractory CD may require treatment with immunosuppressant medications. With the increased identification of specific gluten epitopes and understanding of the pathogenesis of CD, future therapies may rely on genetically altering gluten proteins, immunization techniques, or therapies focused on either the development of specific immune tolerance or regulation of mucosal inflammation.
Collapse
Affiliation(s)
- John H Kwon
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | | |
Collapse
|
|
29
|
Arya S, Rana SS, Sinha SK, Nagi B, Bhasin DK. Celiac disease and chronic calcific pancreatitis with pancreas divisum. Gastrointest Endosc 2006; 63:1080-1. [PMID: 16733138 DOI: 10.1016/j.gie.2006.01.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2005] [Accepted: 01/02/2006] [Indexed: 12/20/2022]
Affiliation(s)
- Sunil Arya
- Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh-160 023, India
| | | | | | | | | |
Collapse
|
|
30
|
Abstract
A variety of hepatic and biliary tract disorders may complicate the clinical course of celiac disease. Some of these have been hypothesized to share common genetic factors or have a common immunopathogenesis, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune forms of hepatitis or cholangitis. Other hepatic changes in celiac disease may be associated with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma. Finally, pancreatic exocrine function may be impaired in celiac disease and represent a cause of treatment failure.
Collapse
MESH Headings
- Celiac Disease/complications
- Celiac Disease/metabolism
- Celiac Disease/pathology
- Cholangitis, Sclerosing/complications
- Cholangitis, Sclerosing/metabolism
- Cholangitis, Sclerosing/pathology
- Fatty Liver/complications
- Fatty Liver/metabolism
- Fatty Liver/pathology
- Gallbladder Diseases/complications
- Gallbladder Diseases/metabolism
- Gallbladder Diseases/pathology
- Hemochromatosis/complications
- Hemochromatosis/metabolism
- Hemochromatosis/pathology
- Hepatitis, Autoimmune/complications
- Hepatitis, Autoimmune/metabolism
- Hepatitis, Autoimmune/pathology
- Humans
- Liver Cirrhosis, Biliary/complications
- Liver Cirrhosis, Biliary/metabolism
- Liver Cirrhosis, Biliary/pathology
- Liver Diseases/complications
- Liver Diseases/metabolism
- Liver Diseases/pathology
- Liver Failure/complications
- Liver Failure/metabolism
- Liver Failure/pathology
- Liver Neoplasms/complications
- Liver Neoplasms/metabolism
- Liver Neoplasms/pathology
- Lymphoma, T-Cell/complications
- Lymphoma, T-Cell/metabolism
- Lymphoma, T-Cell/pathology
- Pancreatic Diseases/complications
- Pancreatic Diseases/metabolism
- Pancreatic Diseases/pathology
Collapse
|
|
31
|
|
|
32
|
Abstract
Coeliac disease is a common condition and its prevalence in UK is now thought to be approximately 1:100. It is being diagnosed and treated more frequently as awareness at the primary care level has increased. Coeliac disease is a complex disorder and is frequently associated with other disease processes. The management of these patients needs to take on a holistic approach, whilst the physician needs to be aware of the rare complications. This article gives an up-to-date review of the literature written on the pathogenesis of coeliac disease. We have attempted to paint a picture from beginning to end, whilst clarifying the grey areas in between. General epidemiological factors are reviewed before looking at genetic risk factors. We assess the sensitivity and specificity of the investigative modalities available for clinical use and comment on optimum management of these patients thereafter. The future of coeliac disease looks promising for patients with several novel therapies on the horizon. Whilst further work is still needed to breed out the toxic epitopes from wheat, novel therapies may come from other areas such as the work aimed at restoring normal tolerance to gluten.
Collapse
Affiliation(s)
- Paul J Ciclitira
- Department of Gastroenterology, GKT, The Rayne Institute, 4th Floor, Lambeth Wing, St Thomas' Hospital, London SE1 7EH, United Kingdom.
| | | | | | | |
Collapse
|
|
33
|
Culliford A, Daly J, Diamond B, Rubin M, Green PHR. The value of wireless capsule endoscopy in patients with complicated celiac disease. Gastrointest Endosc 2005; 62:55-61. [PMID: 15990820 DOI: 10.1016/s0016-5107(05)01566-x] [Citation(s) in RCA: 127] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Celiac disease may be complicated by symptoms that raise the suspicion of small-intestinal malignancy. The objective is to evaluate wireless capsule endoscopy (WCE) in complicated celiac disease. METHODS This is a prospective study at a university referral center. There were 47 patients. The indications for WCE were abdominal pain (57%), cancer surveillance (23%), blood in the stool, or persistent iron deficiency (19%). RESULTS Findings were consistent with celiac disease in 87%: atrophy (68%), fissuring (62%), and mosaic pattern (19%), extending to the ileum in 34%. Unexpected findings were ulceration in 45% (n = 21), cancer (1), polyps (1), stricture (1), submucosal mass (1), ulcerated nodular mucosa (2), and intussusception (1) were seen in 60%. CONCLUSIONS WCE has a high yield in complicated celiac disease, by identifying mucosal abnormalities and by excluding adenocarcinoma.
Collapse
Affiliation(s)
- Andrea Culliford
- Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY, USA
| | | | | | | | | |
Collapse
|
|
34
|
Boynes SG, Moore PA, Shepherd CJ, Bennett CR. Anesthetic management of a patient with celiac disease. ORAL SURGERY, ORAL MEDICINE, ORAL PATHOLOGY, ORAL RADIOLOGY, AND ENDODONTICS 2005; 99:E8-E10. [PMID: 15660078 DOI: 10.1016/j.tripleo.2004.10.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/01/2023]
Abstract
A 22-year-old female with an extensive medical and surgical history that included mental retardation presented for dental treatment under conscious sedation at a special needs clinic. The patient's history revealed a delayed diagnosis of celiac disease (CD) that resulted in growth retardation with poor muscle development. Because of the patient's delayed diagnosis of CD and history of difficult airway management, special considerations were necessary for proper anesthesia administration.
Collapse
|
|
35
|
Ciclitira PJ, Moodie SJ. Transition of care between paediatric and adult gastroenterology. Coeliac disease. Best Pract Res Clin Gastroenterol 2003; 17:181-95. [PMID: 12676114 DOI: 10.1016/s1521-6918(02)00147-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Coeliac disease is a condition in which there is an abnormal mucosa in the small intestine. It improves with a gluten free diet, with avoidance of wheat, rye, barley and possibly oats. The history and epidemiology of this condition are discussed. Diagnosis is based on demonstrating that the characteristic histological abnormalities in the small intestine are dependent on gluten ingestion. Diagnostic pitfalls are discussed. The anti-endomysium and anti-tissue transglutaminase antibodies are specific and sensitive diagnostic tools. The wide variety of clinical symptoms and presentations are discussed including the associated condition of dermatitis herpetiformis. Failure to respond to a gluten-free diet can represent simple dietary problems, an alternative diagnosis or, occasionally, the development of a serious complication of coeliac disease such as ulcerative jejunitis or enteropathy-associated T cell lymphoma. Progress towards the characterization of the toxic epitopes within gluten that exacerbate coeliac disease and our current understanding of the genetics of the disorder are presented.
Collapse
Affiliation(s)
- Paul J Ciclitira
- Department of Gastroenterology, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK.
| | | |
Collapse
|
|
36
|
Abdulkarim AS, Burgart LJ, See J, Murray JA. Etiology of nonresponsive celiac disease: results of a systematic approach. Am J Gastroenterol 2002; 97:2016-21. [PMID: 12190170 DOI: 10.1111/j.1572-0241.2002.05917.x] [Citation(s) in RCA: 228] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Nonresponse or relapse of symptoms is common in patients with celiac disease treated with gluten free diet. Refractory sprue (RS) is defined as initial or subsequent failure of a strict gluten-free diet to restore normal intestinal architecture and function in patients who have celiac-like enteropathy. The aims of this study were: 1) to identify causes of persistent symptoms in patients referred with presumed diagnosis of nonresponsive celiac disease (NCD); and 2) to characterize patients with true RS. METHODS Patients were identified who had been systematically evaluated for NCD between January 1997, and May 2001. Patient records and small bowel biopsy results were reviewed. RESULTS A total of 55 patients were referred with a presumed diagnosis of NCD. Six did not have celiac disease and had other diseases responsible for their symptoms. Diarrhea, abdominal pain, and weight loss were the most common reasons for evaluation in cases of NCD, whereas weight loss, steatorrhea, and diarrhea were the most common presenting features of RS (nine patients). Of the 49 patients with celiac disease, 25 were identified as having gluten contamination. Additional diagnoses accounting for persistent symptoms included: pancreatic insufficiency, irritable bowel syndrome, bacterial overgrowth, lymphocytic colitis, collagenous colitis, ulcerative jejunitis, T-cell lymphoma, pancreatic cancer, fructose intolerance, protein losing enteropathy, cavitating lymphadenopathy syndrome, and tropical sprue. CONCLUSIONS Based on this study, we conclude the following: 1) gluten contamination is the leading reason for NCD; 2) of NCD cases, 18% are due to RS; and 3) alternative diseases or those coexistent with celiac disease and gluten contamination should be ruled out before a diagnosis of RS is made.
Collapse
Affiliation(s)
- Ahmad S Abdulkarim
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | | |
Collapse
|
|
37
|
Abdulkarim AS, Murray JA. Celiac Disease. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2002; 5:27-38. [PMID: 11792235 DOI: 10.1007/s11938-002-0004-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Individuals with celiac disease present with a wide array of symptoms and signs. Celiac disease can result in substantial injury to the small intestine, deleterious effects on other organ systems, and an overall doubling of mortality. The role of the gastroenterologist is primarily to make the diagnosis and then to ensure that patients with celiac disease receive up-to-date and accurate instructions on diet. It is our opinion that gastroenterologists should participate in the follow-up of what is in fact a form of inflammatory bowel disease. The failure to identify and treat patients with substantial problems may result in an excess of preventable morbidity and mortality. Intestinal biopsy is the definitive method of making the diagnosis of celiac disease, provided the patient has not excluded gluten from his or her diet, because exclusion of gluten results in negative serologic test results and normal small intestinal biopsy samples. The removal of gluten from the diet can result in a total recovery of gut function and a correction of most other consequences. The response is usually so complete that patients should consider themselves to be basically healthy as long as they stay away from the offending foods. However, the execution and maintenance of the "theoretically simple" exclusion of gluten is difficult. The condition is permanent and mandates adherence to a lifelong gluten-free diet; even small amounts of gluten can result in injury to the intestinal lining. The diet is restrictive and requires the patient to be careful about food choices. Therefore, patient education and motivation are crucial to a successful outcome. The correction of vitamin and mineral deficiencies may be helpful in aiding recovery; vitamin D and calcium supplementation often is recommended. No drug therapy has been proven to suppress the disease.
Collapse
Affiliation(s)
- Ahmad S. Abdulkarim
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Mayo Building W19, Rochester, MN 55905, USA.
| | | |
Collapse
|
|
38
|
Affiliation(s)
- Richard J Farrell
- Gastroenterology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
| | | |
Collapse
|
|
39
|
Ciclitira PJ, King AL, Fraser JS. AGA technical review on Celiac Sprue. American Gastroenterological Association. Gastroenterology 2001; 120:1526-40. [PMID: 11313324 DOI: 10.1053/gast.2001.24056] [Citation(s) in RCA: 246] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- P J Ciclitira
- Gastroenterology Unit (GKT), The Rayne Institute, St. Thomas' Hospital, London, England
| | | | | |
Collapse
|
|
40
|
Abstract
A minority of patients with coeliac disease do not improve in spite of strictly adhering to gluten-free diet and are considered to have developed refractory disease. Such patients are usually treated with steroid and/or immunosuppressive agents but these are not without serious side effects. Herein, we present a patient with refractory coeliac disease in whom remarkable clinical and histological improvement was achieved on elemental diet. Elemental diet should be considered as a treatment option in such patients.
Collapse
Affiliation(s)
- A Mandal
- Gastrointestinal Research Unit, Leicester General Hospital, UK.
| | | |
Collapse
|
|
41
|
Abstract
Celiac disease is a gluten-sensitive enteropathy, characterized by villous atrophy, which is reversed by gluten withdrawal. A minority of patients with celiac-like enteropathy are resistant to gluten-free diet, so-called refractory sprue, or unclassified sprue. Refractory sprue is a diagnosis of exclusion; all other causes of a celiac-like enteropathy must be eliminated before a diagnosis of refractory sprue can be made. Recent evidence suggests that refractory sprue comprises a heterogenous group of patients with diverse underlying causes. A small proportion of these patients seem to have an adult form of autoimmune enteropathy, characterized by the presence of antienterocyte antibodies. However, a larger group of patients with refractory sprue now seem to have a cryptic intestinal T-cell lymphoma, characterized by the presence of phenotypically abnormal, monoclonal intraepithelial lymphocytes, despite benign cytology. Current therapeutic options include nutritional support and immunosuppressive therapy, but response is variable. The prognosis of refractory sprue may be poor; patients may die of severe malabsorption, or through synchronous or metachronous development of an enteropathy-associated T-cell lymphoma. Based on this recent evidence, patients with refractory sprue should be screened for antienterocyte antibodies and have T-cell receptor and monoclonal antibody studies performed; this could facilitate identification of cases of adult-onset autoimmune enteropathy and those of cryptic T-cell lymphoma. Moreover, early recognition of the malignant nature of the intestinal infiltrate in some cases of refractory sprue could permit the development of novel chemotherapeutic regimens for this condition.
Collapse
Affiliation(s)
- B M Ryan
- Department of Gastroenterology and Clinical Medicine, St. James's Hospital and Trinity College, Dublin, Ireland
| | | |
Collapse
|
|
42
|
Robert ME, Ament ME, Weinstein WM. The histologic spectrum and clinical outcome of refractory and unclassified sprue. Am J Surg Pathol 2000; 24:676-87. [PMID: 10800986 DOI: 10.1097/00000478-200005000-00006] [Citation(s) in RCA: 72] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The vast majority of patients with celiac disease respond to a gluten-free diet; yet, a small number of refractory patients do not respond and have persistent malabsorption and residual mucosal abnormalities of the small intestine. The histologic features of refractory/unclassified sprue have been published as case reports, often without long-term follow up, and no clear histologic picture has emerged. We present the results of a long-term study of the clinical and histologic features of 10 patients with refractory/unclassified sprue. The histologic features of small bowel biopsies in this group of patients were compared with those of 10 patients with responsive celiac disease and with 10 patients without malabsorption who had normal duodenal biopsies. Five of the 10 refractory patients ultimately developed collagenous sprue as a distinct histologic marker of refractory disease. Additional distinctive findings found in small bowel biopsies in the refractory group were subcryptal chronic inflammation (10 of 10) and marked mucosal thinning in three patients. Other nonspecific findings included acute inflammation and gastric metaplasia. One patient with collagenous sprue developed a B-cell lymphoma of the ileum, and in general collagenous sprue was associated with a poor prognosis. Two of five patients died whereas two others require total parenteral nutrition for survival. Pathologists evaluating small bowel biopsies in the setting of malabsorption should be aware of the subtle histologic changes described here that may portend a refractory course.
Collapse
Affiliation(s)
- M E Robert
- Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520-8023, USA
| | | | | |
Collapse
|
|
43
|
Abstract
BACKGROUND Celiac disease is associated with pancreatico-biliary disease. Postulated mechanisms include reduced gallbladder emptying due to impaired cholecystokinin release and pancreatitis due to malnutrition. We hypothesize that celiac disease may also be associated with pancreatico-biliary abnormalities due to duodenal inflammation and papillary stenosis. METHODS Over a 48-month period, 169 patients referred for possible sphincter of Oddi dysfunction who underwent pancreatico-biliary manometry were tested for gliadin and endomysial antibodies. Duodenal and papillary biopsies were preformed in those patients who were positive. RESULTS Celiac disease was diagnosed in 12 (7.1%; 3 men, 9 women). The mean age was 61 years as compared with 37 years for those patients without celiac disease. All of the celiac patients had been referred for recurrent abdominal pain and/or idiopathic pancreatitis. Ten had idiopathic recurrent pancreatitis with elevated amylase and lipase levels. Two of these patients also had mildly elevated liver function tests associated with the abdominal pain. Only 3 of 12 patients had a prior diagnosis of celiac disease. These 12 patients had manometric evidence of stenosis and histologic evidence of periampullary inflammation as well as histologic changes consistent with celiac disease. In 10 of 12 patients sphincterotomy or extension of a prior papillotomy was performed. Two patients were treated with a gluten-free diet alone. CONCLUSIONS We describe 12 patients with papillary stenosis and celiac disease. In 9 cases the celiac disease was a new diagnosis. Celiac disease should be considered in the etiology of papillary stenosis or idiopathic recurrent pancreatitis.
Collapse
Affiliation(s)
- R S Patel
- Department of Gastroenterology and Hepatology, University of Iowa College of Medicine, Iowa City, Iowa, USA
| | | | | |
Collapse
|
|
44
|
Abstract
We report a patient with life-threatening refractory sprue who was dependent on high doses of corticosteroids to prevent severe diarrhea, malabsorption, and villous atrophy. Azathioprine allowed tapering of corticosteroids to lower doses, while maintaining remission in histology and in objective measures of malabsorption. Immunosuppressive therapy, however, is not without risks, particularly in patients with associated hypoglobulinemia.
Collapse
Affiliation(s)
- A Vaidya
- Department of Gastroenterology, Christ Hospital, University of Illinois, Oak Lawn, 60453, USA
| | | | | |
Collapse
|
|
45
|
Przemioslo RT, Kontakou M, Nobili V, Ciclitira PJ. Raised pro-inflammatory cytokines interleukin 6 and tumour necrosis factor alpha in coeliac disease mucosa detected by immunohistochemistry. Gut 1994; 35:1398-403. [PMID: 7959194 PMCID: PMC1375013 DOI: 10.1136/gut.35.10.1398] [Citation(s) in RCA: 77] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The levels of two pro-inflammatory cytokines, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha), in coeliac disease were studied by immunohistochemistry. Jejunal biopsy specimens from patients with untreated disease, (n = 11), treated disease (n = 9), and normal controls, (n = 11) were stained to detect IL-6, TNF-alpha, CD45 (pan-leukocyte), and CD68 (macrophage surface antigen). Positive cells were identified in the epithelium (per 100 enterocytes) and in the lamina propria (per unit area). There was a significant increase in median IL-6 and TNF-alpha staining in both the lamina propria and the epithelium of untreated coeliac disease patients (lamina propria, 16.2 and 13.0 respectively; epithelium, 0.86 and 1.21, all p < 0.05) when compared with treated coeliac disease patients (lamina propria; 6.0 and 6.2, epithelium; 0.60 and 0.60) and controls (lamina propria; 6.5 and 7.5, epithelium; 0.58 and 0.60). A significant increase in the number of CD45 positive cells was found in the untreated coeliac disease lamina propria and epithelium (p < 0.05) but this was accompanied by a significant rise in CD68 positive cells in the lamina propria only (p < 0.05). Increased IL-6 and TNF-alpha in the lamina propria and epithelium of patients with untreated coeliac disease further supports their role in the immune pathogenesis of this disorder.
Collapse
Affiliation(s)
- R T Przemioslo
- Gastroenterology Unit UMDS, St Thomas's Hospital, London
| | | | | | | |
Collapse
|
|
46
|
Abstract
A small bowel enema was performed in patients with non-responsive coeliac disease, in coeliac patients on a normal diet (untreated) and those who had shown a good response to a gluten free diet, and in control subjects to determine whether there were any specific radiological features of the non-responsive state. A significant reduction in the average number of jejunal folds and an increase in the number of ileal folds (reversal of the jejunoileal fold pattern) was found in eight of nine non-responsive coeliac patients, one of seven untreated coeliac patients, and in none of the good responders or control subjects. This pattern identifies coeliac patients with a poor response to a gluten free diet who are likely to suffer major complications.
Collapse
Affiliation(s)
- N Mike
- Alistair Frazer and John Squire Clinical Investigation Unit, Birmingham
| | | | | | | |
Collapse
|
|
47
|
Affiliation(s)
- P D Howdle
- Department of Medicine, St. James's University Hospital, Leeds
| | | |
Collapse
|
|
48
|
Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 53-1987. A 55-year-old woman with one year of malabsorption and the recent development of abdominal pain. N Engl J Med 1987; 317:1715-28. [PMID: 3696179 DOI: 10.1056/nejm198712313172707] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
|
|
49
|
Savilahti E, Pelkonen P, Holmberg C, Perkkiö M, Unsworth J. Fatal unresponsive villous atrophy of the jejunum, connective tissue disease and diabetes in a girl with intestinal epithelial cell antibody. ACTA PAEDIATRICA SCANDINAVICA 1985; 74:472-6. [PMID: 4003075 DOI: 10.1111/j.1651-2227.1985.tb11011.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The patient presented with a diabetes at the age of 3 years. At the age of 5 years she got persistent diarrhoea, lost weight and showed symptoms or arthritis and pericarditis. She was found to have total villous atrophy of the jejunum, which did not respond to dietary treatment, total parental nutrition, prednisone and cyclophosphamide medication. She had high titres of antinuclear antibodies and elevated serum IgG, but antibodies to DNA and to ribonuclearprotein were negative. A low titre of antibodies to human intestinal epithelial cells was found. The patient died of overwhelming fungal sepsis. We propose that the intestinal damage is part of the autoimmune disease. Careful study of jejunal biopsy specimens is helpful in distinguishing this type of patient from patients with coeliac disease.
Collapse
|
|
50
|
Kluge F, Koch HK, Köttgen E, Gerok W. [Gluten-sensitive enteropathy--in the light of new clinical and pathogenetic aspects]. KLINISCHE WOCHENSCHRIFT 1983; 61:669-79. [PMID: 6350694 DOI: 10.1007/bf01487612] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
The corn protein gluten causes the gluten-sensitive enteropathy in susceptible persons (HLA-antigens). The diagnosis is made on the basis of the morphological criteria of villous atrophy of the jejunal mucosa and the clinical observation that the malabsorption can be healed by a gluten-free diet. The disease, which occurs in children and adults, is a distinct entity. Life-long adherence to a gluten-free diet is difficult. Intentional or unintentional reintroduction of gluten often causes masked disease states. These are best classified on the basis of electron-microscopy study of the jejunal biopsy. We propose a new classification of the phases of remission. A group of diseases exist which are closely related to gluten-sensitive enteropathy. Frequently villous atrophy is detectable. However, the disease does not respond to a gluten-free diet. The pathophysiology of these diseases is at present unclear. Diseases involving autoimmune processes also appear to be associated with gluten-sensitive enteropathy. The common factor is probably an immuno-genetic defect. This is supported by the existence of common HLA-antigen constellations. Gluten has been characterised in vitro as a lectin with oligomannose specificity. This provides a new pathomechanism for the gluten induced enterocytic destruction.
Collapse
|