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Doukas SG, Doukas PG, Velpari S. Non-celiac Enteropathy and Olmesartan: An Essential Consideration. Cureus 2024; 16:e54373. [PMID: 38505463 PMCID: PMC10948264 DOI: 10.7759/cureus.54373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2024] [Indexed: 03/21/2024] Open
Abstract
Emerging evidence has shed light on non-celiac causes of enteropathy in recent years, presenting a diagnostic challenge for clinicians. This study discusses the diagnostic challenges related to non-celiac enteropathy, specifically focusing on olmesartan-induced enteropathy (OIE). A 73-year-old lady presented to the emergency department with a six-month history of watery diarrhea exacerbated by food intake and significant weight loss. The patient at admission was found to be dehydrated with severe hypokalemia and hypocalcemia. The extensive testing that was performed was unremarkable, including celiac disease panel, enteric panel, ova and parasites, Clostridium difficile, fecal calprotectin, and computed tomography of the abdomen and pelvis. A significant electrolyte imbalance was corrected at admission, and subsequent upper endoscopy investigation with duodenal biopsies revealed moderate to severe villi blunting with a significant intraepithelial infiltrate of CD3+ lymphocytes. A colonoscopy that was performed at the same time was unremarkable, with negative biopsies for microscopic colitis. Given the suspicion of OIE, olmesartan was discontinued. One-month follow-up revealed resolution of malabsorption, with electrolyte normalization and duodenal biopsies showing improved duodenitis. This study emphasizes the importance of considering medication history and ruling out other potential causes of enteropathy. Olmesartan is an angiotensin II receptor antagonist that is commonly prescribed for hypertension. However, in rare cases, it may induce enteropathy, which often remains underdiagnosed. This rare side effect may present as chronic diarrhea, weight loss, and signs of malabsorption. Interestingly, OIE presents with overlapping clinical and histopathological features to celiac disease and, therefore, may mislead physicians to an extensive diagnostic investigation. Greater awareness of medication-related diarrheal syndromes such as OIE should be promoted, given that simple discontinuation of the medication can lead to dramatic clinical improvement.
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Affiliation(s)
- Sotirios G Doukas
- Department of Medicine, Section of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School/Saint Peter's University Hospital, New Brunswick, USA
| | - Panagiotis G Doukas
- Department of Medicine, Rutgers-Robert Wood Johnson Medical School/Saint Peter's University Hospital, New Brunswick, USA
| | - Sugirdhana Velpari
- Department of Medicine, Section of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School/Saint Peter's University Hospital, New Brunswick, USA
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Jiang C, Barkin JA, Barkin JS. Exocrine Pancreatic Insufficiency Is Common in Celiac Disease: A Systematic Review and Meta-Analysis. Dig Dis Sci 2023:10.1007/s10620-023-07965-7. [PMID: 37294459 DOI: 10.1007/s10620-023-07965-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 07/18/2022] [Indexed: 06/10/2023]
Abstract
The prevalence of celiac disease (CD) is approximately 1% in the US. Studies have shown possible association between exocrine pancreatic insufficiency (EPI) and CD, with numerous hypothesized biological mechanisms including small bowel mucosal damage causing disruption of enteric-mediated hormonal secretion such as cholecystokinin and loss of enterokinase. The overall prevalence of EPI in CD remains unknown. We performed systematic review and metanalysis and examined the prevalence of EPI in patients who were first diagnosed with CD versus those who had been on treatment with gluten-free diet (GFD). Results Six studies were included in the analysis totaling 446 CD patients (Avg age 44.1 years; 34% Males). One hundred and forty-four patients had newly diagnosed CD, and 302 patients had known CD with at least 9 months treatment with GFD. Four studies examined newly diagnosed CD patients. The individual rates of EPI in new CD patients ranged from 10.5 to 46.5%. The pooled prevalence of EPI in newly diagnosed CD patients was 26.2% (95% CI 8.43-43.92%, Q = 2.24, I2 = 0%). Five studies examined CD patients on GFD. The rate of EPI ranged from 1.9% to 18.2%. The prevalence of EPI in patients treated with GFD is 8% (95% CI 1.52-14.8%, Q = 4.42, I2 = 9.59%). Patients with newly diagnosed CD are significantly more likely to have EPI compared to those patients treated with GFD (p = 0.031). CD patients on GFD with persistent symptoms have a significantly higher rate of EPI (28.4%) compared to CD patients on GFD who are asymptomatic (3%) (p < 0.001).
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Affiliation(s)
- Chunsu Jiang
- Division of Gastroenterology, University of Miami/Jackson Memorial Hospital, Miami, USA.
| | - Jodie A Barkin
- Division of Gastroenterology, University of Miami/Jackson Memorial Hospital, Miami, USA
| | - Jamie S Barkin
- Division of Gastroenterology, University of Miami/Jackson Memorial Hospital, Miami, USA
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Conti Bellocchi MC, Crinò SF, De Marchi G, De Pretis N, Ofosu A, Caldart F, Ciccocioppo R, Frulloni L. A Clinical and Pathophysiological Overview of Intestinal and Systemic Diseases Associated with Pancreatic Disorders: Causality or Casualty? Biomedicines 2023; 11:biomedicines11051393. [PMID: 37239064 DOI: 10.3390/biomedicines11051393] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 05/01/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023] Open
Abstract
The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic.
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Affiliation(s)
| | - Stefano Francesco Crinò
- Diagnostic and Interventional Endoscopy of Pancreas, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Giulia De Marchi
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Nicolò De Pretis
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Andrew Ofosu
- Division of Gastroenterology and Hepatology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
| | - Federico Caldart
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Luca Frulloni
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
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Whitcomb DC, Duggan SN, Martindale R, Lowe M, Stallings VA, Conwell D, Barkin JA, Papachristou GI, Husain SZ, Forsmark CE, Kaul V. AGA-PancreasFest Joint Symposium on Exocrine Pancreatic Insufficiency. GASTRO HEP ADVANCES 2022; 2:395-411. [PMID: 39132652 PMCID: PMC11307793 DOI: 10.1016/j.gastha.2022.11.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 11/03/2022] [Indexed: 08/13/2024]
Abstract
Exocrine pancreatic insufficiency (EPI) is a clinically defined syndrome based on the physician's assessment of a patient's maldigestion. However, current clinical definitions are inadequate in determining (1) the threshold of reduced pancreatic digestive enzyme secretion that determines "pancreatic insufficiency" in an individual patient; (2) the role of pancreatic function tests; (3) effects of differing metabolic needs, nutrition intake, and intestinal function/adaptation (4) when pancreatic enzyme replacement therapy is needed; and (5) how to monitor and titrate multiple therapies. Experts and key opinion leaders were invited to PancreasFest 2021 to discuss and help clarify mechanistic issues critical to defining EPI and to address misconceptions and barriers limiting advancements in patient care. Clinically EPI is defined as inadequate delivery of pancreatic digestive enzymes to meals to meet nutritional needs and is reversed with appropriate treatment. A new mechanistic definition of EPI was proposed that includes the disorders essence and character: (1) EPI is a disorder caused by failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine in concert with ingested nutrients, followed by enzymatic digestion of a series of individual snacks and meals over time to meet nutritional and metabolic needs, given (a) the specific macronutritional and micronutritional needs; (b) nutrient intake; (c) exocrine pancreatic function; and (d) intestinal anatomy, function, diseases, and adaptative capacity. (2) EPI is characterized by variable deficiencies in micronutrients and macronutrients, especially essential fats and fat-soluble vitamins, by gastrointestinal symptoms of nutrient maldigestion and by improvement or correction of nutritional state with lifestyle changes, disease treatment, optimized diet, dietary supplements, and/or administration of adequate pancreatic enzyme replacement therapy. EPI is complex and individualized and multidisciplinary approaches are needed to optimize therapy. Better pancreas function tests and biomarkers are needed to diagnose EPI and guide treatment.
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Affiliation(s)
- David C. Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Cell Biology and Molecular Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Sinead N. Duggan
- Department of Surgery, School of Medicine, Trinity College Dublin, Tallaght University Hospital, Dublin, Republic of Ireland
| | - Robert Martindale
- Department of Surgery, Oregon Health and Science University, Portland, Oregon
| | - Mark Lowe
- Department of Pediatric Science, Washington University School of Medicine, St. Louis, Missouri
| | - Virginia A. Stallings
- Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Darwin Conwell
- Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky
| | - Jodie A. Barkin
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida
| | - Georgios I. Papachristou
- Division of Gastroenterology, Department of Medicine, Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Sohail Z. Husain
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Stanford School of Medicine and Stanford Medicine Children's Health, Stanford, California
| | - Christopher E. Forsmark
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Florida, Gainesville, Florida
| | - Vivek Kaul
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Rochester Medical Center, Rochester, New York
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Pancreatic Enzyme Replacement Therapy in Patients with Non-pancreatic Digestive Conditions: A Nationwide Claims Analysis. Dig Dis Sci 2022; 68:1754-1761. [PMID: 36370243 DOI: 10.1007/s10620-022-07750-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 10/25/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND AND AIMS Pancreatic enzyme replacement therapy (PERT) is most commonly used to treat exocrine insufficiency related to pancreatic diseases, but can be used for non-pancreatic digestive conditions (NPDC). We aimed to determine the prevalence of PERT use and describe prescription patterns in individuals with NPDC. METHODS A nationally representative claims database of 48.6 million enrollees was used to identify individuals who received PERT prescription(s) in the absence of any pancreas-related diagnosis. Data on demographics, enrolment, comorbidities, exocrine function testing, treatment and potential indications for PERT were retrieved, and compared with individuals who received PERT for primary diagnosis of chronic pancreatitis (CP). RESULTS A total of 29,234 individuals (64.1% female, mean age 52.4 ± 16.5 years) received PERT for NPDC. The overall estimated US population prevalence rate for PERT use for NDPC was 60.2/100,000 persons. Rates increased significantly with age and were higher in women in all age groups except 1-20 years old. When compared with CP, individuals with NPDC receiving PERT were more likely to be older (52.4 vs. 50.1 years), female (64.1% vs. 51.0%), have lower prevalence of alcoholism (3.6% vs. 25.0%), tobacco abuse (8.4% vs. 30.1%), and received PERT for shorter mean duration (5.3 vs. 8.2 months) (all p < 0.001). Median dose of PERT in individuals with NPDC was 2880 lipase units/day. CONCLUSIONS Although proportionally low, a sizable population receives PERT for NPDC. PERT for NPDC is usually prescribed at a low dose and for shorter duration, suggesting it is used mostly as a trial for or until resolution of symptoms.
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Balaban DV, Enache I, Ciochina M, Popp A, Jinga M. Pancreatic involvement in celiac disease. World J Gastroenterol 2022; 28:2680-2688. [PMID: 35979168 PMCID: PMC9260863 DOI: 10.3748/wjg.v28.i24.2680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 04/17/2022] [Accepted: 05/27/2022] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is well recognized as a systemic, chronic autoimmune disease mainly characterized by gluten-sensitive enteropathy in genetically predisposed individuals but with various extraintestinal features. One of the affected organs in CD is the pancreas, consisting of both endocrine and exocrine alterations. Over the last decades there has been increasing interest in the pancreatic changes in CD, and this has been reflected by a great number of publications looking at this extraintestinal involvement during the course of CD. While pancreatic endocrine changes in CD, focusing on type 1 diabetes mellitus, are well documented in the literature, the relationship with the exocrine pancreas has been less studied. This review summarizes currently available evidence with regard to pancreatic exocrine alterations in CD, focusing on risk of pancreatitis in CD patients, association with autoimmune pancreatitis, prevalence and outcomes of pancreatic exocrine insufficiency in newly diagnosed and gluten-free diet treated CD patients, and the link with cystic fibrosis. In addition, we discuss mechanisms behind the associated pancreatic exocrine impairment in CD and highlight the recommendations for clinical practice.
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Affiliation(s)
- Daniel Vasile Balaban
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Iulia Enache
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Marina Ciochina
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Alina Popp
- Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- National Institute for Mother and Child Health, Bucharest 020021, Romania
| | - Mariana Jinga
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
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7
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Kunovský L, Dítě P, Jabandžiev P, Eid M, Poredská K, Vaculová J, Sochorová D, Janeček P, Tesaříková P, Blaho M, Trna J, Hlavsa J, Kala Z. Causes of Exocrine Pancreatic Insufficiency Other Than Chronic Pancreatitis. J Clin Med 2021; 10:jcm10245779. [PMID: 34945075 PMCID: PMC8708123 DOI: 10.3390/jcm10245779] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 11/30/2021] [Accepted: 12/02/2021] [Indexed: 12/12/2022] Open
Abstract
Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malnutrition, results from primary pancreatic disease or is secondary to impaired exocrine pancreatic function. Although chronic pancreatitis is the most common cause of EPI, several additional causes exist. These include pancreatic tumors, pancreatic resection procedures, and cystic fibrosis. Other diseases and conditions, such as diabetes mellitus, celiac disease, inflammatory bowel disease, and advanced patient age, have also been shown to be associated with EPI, but the exact etiology of EPI has not been clearly elucidated in these cases. The causes of EPI can be divided into loss of pancreatic parenchyma, inhibition or inactivation of pancreatic secretion, and postcibal pancreatic asynchrony. Pancreatic enzyme replacement therapy (PERT) is indicated for the conditions described above presenting with clinically clear steatorrhea, weight loss, or symptoms related to maldigestion and malabsorption. This review summarizes the current literature concerning those etiologies of EPI less common than chronic pancreatitis, the pathophysiology of the mechanisms of EPI associated with each diagnosis, and treatment recommendations.
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Affiliation(s)
- Lumír Kunovský
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (L.K.); (P.D.); (K.P.); (J.V.)
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (D.S.); (P.J.); (Z.K.)
| | - Petr Dítě
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (L.K.); (P.D.); (K.P.); (J.V.)
- Department of Gastroenterology and Internal Medicine, University Hospital Ostrava, Faculty of Medicine, University of Ostrava, 70852 Ostrava, Czech Republic;
| | - Petr Jabandžiev
- Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, 61300 Brno, Czech Republic;
- Central European Institute of Technology, Masaryk University, 62500 Brno, Czech Republic
| | - Michal Eid
- Department of Hematology, Oncology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic;
| | - Karolina Poredská
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (L.K.); (P.D.); (K.P.); (J.V.)
| | - Jitka Vaculová
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (L.K.); (P.D.); (K.P.); (J.V.)
| | - Dana Sochorová
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (D.S.); (P.J.); (Z.K.)
| | - Pavel Janeček
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (D.S.); (P.J.); (Z.K.)
| | - Pavla Tesaříková
- Department of Internal Medicine, Hospital Boskovice, 68001 Boskovice, Czech Republic;
| | - Martin Blaho
- Department of Gastroenterology and Internal Medicine, University Hospital Ostrava, Faculty of Medicine, University of Ostrava, 70852 Ostrava, Czech Republic;
| | - Jan Trna
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (L.K.); (P.D.); (K.P.); (J.V.)
- Department of Internal Medicine, Hospital Boskovice, 68001 Boskovice, Czech Republic;
- Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute Brno, 60200 Brno, Czech Republic
- Correspondence: (J.T.); (J.H.)
| | - Jan Hlavsa
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (D.S.); (P.J.); (Z.K.)
- Correspondence: (J.T.); (J.H.)
| | - Zdeněk Kala
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic; (D.S.); (P.J.); (Z.K.)
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8
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Phillips ME, Hopper AD, Leeds JS, Roberts KJ, McGeeney L, Duggan SN, Kumar R. Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000643. [PMID: 34140324 PMCID: PMC8212181 DOI: 10.1136/bmjgast-2021-000643] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/08/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Pancreatic exocrine insufficiency is a finding in many conditions, predominantly affecting those with chronic pancreatitis, pancreatic cancer and acute necrotising pancreatitis. Patients with pancreatic exocrine insufficiency can experience gastrointestinal symptoms, maldigestion, malnutrition and adverse effects on quality of life and even survival.There is a need for readily accessible, pragmatic advice for healthcare professionals on the management of pancreatic exocrine insufficiency. METHODS AND ANALYSIS A review of the literature was conducted by a multidisciplinary panel of experts in pancreatology, and recommendations for clinical practice were produced and the strength of the evidence graded. Consensus voting by 48 pancreatic specialists from across the UK took place at the 2019 Annual Meeting of the Pancreatic Society of Great Britain and Ireland annual scientific meeting. RESULTS Recommendations for clinical practice in the diagnosis, initial management, patient education and long term follow up were developed. All recommendations achieved over 85% consensus and are included within these comprehensive guidelines.
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Affiliation(s)
- Mary E Phillips
- Nutrition and Dietetics, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
| | - Andrew D Hopper
- Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - John S Leeds
- HPB Unit, Freeman Hospital, Newcastle Upon Tyne, Tyne and Wear, UK
| | - Keith J Roberts
- HPB Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Laura McGeeney
- Nutrition and Dietetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Sinead N Duggan
- Department of Surgery, Trinity College Dublin, Dublin, Ireland
| | - Rajesh Kumar
- HPB Surgery, Royal Surrey Hospital NHS Foundation Trust, Guildford, UK
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Lam KW, Leeds J. How to manage: patient with a low faecal elastase. Frontline Gastroenterol 2019; 12:67-73. [PMID: 33489070 PMCID: PMC7802491 DOI: 10.1136/flgastro-2018-101171] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 10/31/2019] [Accepted: 11/04/2019] [Indexed: 02/06/2023] Open
Affiliation(s)
- Kwan Wai Lam
- Pancreaticobiliary Medicine, Freeman Hospital, Newcastle upon Tyne, Newcastle upon Tyne, UK
| | - John Leeds
- Pancreaticobiliary Medicine, Freeman Hospital, Newcastle upon Tyne, Newcastle upon Tyne, UK
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10
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Chronic Pancreatitis is a Common Finding in Celiac Patients Who Undergo Endoscopic Ultrasound. J Clin Gastroenterol 2019; 53:e128-e129. [PMID: 27749638 DOI: 10.1097/mcg.0000000000000726] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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11
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Sanctuary MR, Kain JN, Angkustsiri K, German JB. Dietary Considerations in Autism Spectrum Disorders: The Potential Role of Protein Digestion and Microbial Putrefaction in the Gut-Brain Axis. Front Nutr 2018; 5:40. [PMID: 29868601 PMCID: PMC5968124 DOI: 10.3389/fnut.2018.00040] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 04/30/2018] [Indexed: 12/13/2022] Open
Abstract
Children with autism spectrum disorders (ASD), characterized by a range of behavioral abnormalities and social deficits, display high incidence of gastrointestinal (GI) co-morbidities including chronic constipation and diarrhea. Research is now increasingly able to characterize the “fragile gut” in these children and understand the role that impairment of specific GI functions plays in the GI symptoms associated with ASD. This mechanistic understanding is extending to the interactions between diet and ASD, including food structure and protein digestive capacity in exacerbating autistic symptoms. Children with ASD and gut co-morbidities exhibit low digestive enzyme activity, impaired gut barrier integrity and the presence of antibodies specific for dietary proteins in the peripheral circulation. These findings support the hypothesis that entry of dietary peptides from the gut lumen into the vasculature are associated with an aberrant immune response. Furthermore, a subset of children with ASD exhibit high concentrations of metabolites originating from microbial activity on proteinaceous substrates. Taken together, the combination of specific protein intakes poor digestion, gut barrier integrity, microbiota composition and function all on a background of ASD represents a phenotypic pattern. A potential consequence of this pattern of conditions is that the fragile gut of some children with ASD is at risk for GI symptoms that may be amenable to improvement with specific dietary changes. There is growing evidence that shows an association between gut dysfunction and dysbiosis and ASD symptoms. It is therefore urgent to perform more experimental and clinical research on the “fragile gut” in children with ASD in order to move toward advancements in clinical practice. Identifying those factors that are of clinical value will provide an evidence-based path to individual management and targeted solutions; from real time sensing to the design of diets with personalized protein source/processing, all to improve GI function in children with ASD.
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Affiliation(s)
- Megan R Sanctuary
- Department of Nutrition, University of California, Davis, Davis, CA, United States
| | - Jennifer N Kain
- Department of Neurobiology, Physiology and Behavior Department, University of California, Davis, Davis, CA, United States
| | - Kathleen Angkustsiri
- School of Medicine, Department of Pediatrics, University of California, Davis, Sacramento, CA, United States.,Department of Pediatrics, UC Davis MIND Institute, Sacramento, CA, United States
| | - J Bruce German
- Department of Food Science and Technology, University of California, Davis, Davis, CA, United States.,Foods for Health Institute, University of California, Davis, Davis, CA, United States
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12
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Singh VK, Haupt ME, Geller DE, Hall JA, Quintana Diez PM. Less common etiologies of exocrine pancreatic insufficiency. World J Gastroenterol 2017; 23:7059-7076. [PMID: 29093615 PMCID: PMC5656454 DOI: 10.3748/wjg.v23.i39.7059] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 05/27/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
Abstract
Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases (diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin (CCK); celiac or inflammatory bowel disease (IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery (asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy (PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI (66%-92%). EPI occurs in patients with type 1 (26%-57%) or type 2 diabetes (20%-36%) and is typically mild to moderate; by definition, all patients with type 3c (pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease (4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD (14%-74%) and up to 100% of gastrointestinal surgery patients (47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT.
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Affiliation(s)
- Vikesh K Singh
- Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Mark E Haupt
- Medical Affairs, AbbVie Inc., North Chicago, IL 60064, United States
| | - David E Geller
- Cystic Fibrosis Clinical Development, AbbVie Inc., North Chicago, IL 60064, United States
| | - Jerry A Hall
- CREON® Clinical Development, AbbVie Inc., North Chicago, IL 60064, United States
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DALLAS DAVIDC, SANCTUARY MEGANR, QU YUNYAO, KHAJAVI SHABNAMHAGHIGHAT, VAN ZANDT ALEXANDRIAE, DYANDRA MELISSA, FRESE STEVENA, BARILE DANIELA, GERMAN JBRUCE. Personalizing protein nourishment. Crit Rev Food Sci Nutr 2017; 57:3313-3331. [PMID: 26713355 PMCID: PMC4927412 DOI: 10.1080/10408398.2015.1117412] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Proteins are not equally digestible-their proteolytic susceptibility varies by their source and processing method. Incomplete digestion increases colonic microbial protein fermentation (putrefaction), which produces toxic metabolites that can induce inflammation in vitro and have been associated with inflammation in vivo. Individual humans differ in protein digestive capacity based on phenotypes, particularly disease states. To avoid putrefaction-induced intestinal inflammation, protein sources, and processing methods must be tailored to the consumer's digestive capacity. This review explores how food processing techniques alter protein digestibility and examines how physiological conditions alter digestive capacity. Possible solutions to improving digestive function or matching low digestive capacity with more digestible protein sources are explored. Beyond the ileal digestibility measurements of protein digestibility, less invasive, quicker and cheaper techniques for monitoring the extent of protein digestion and fermentation are needed to personalize protein nourishment. Biomarkers of protein digestive capacity and efficiency can be identified with the toolsets of peptidomics, metabolomics, microbial sequencing and multiplexed protein analysis of fecal and urine samples. By monitoring individual protein digestive function, the protein component of diets can be tailored via protein source and processing selection to match individual needs to minimize colonic putrefaction and, thus, optimize gut health.
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Affiliation(s)
- DAVID C. DALLAS
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Foods for Health Institute, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - MEGAN R. SANCTUARY
- Foods for Health Institute, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Department of Nutrition, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - YUNYAO QU
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - SHABNAM HAGHIGHAT KHAJAVI
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Department of Food Science and Technology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - ALEXANDRIA E. VAN ZANDT
- Department of Nutrition, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - MELISSA DYANDRA
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - STEVEN A. FRESE
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Foods for Health Institute, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - DANIELA BARILE
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Foods for Health Institute, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - J. BRUCE GERMAN
- Department of Food Science and Technology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Foods for Health Institute, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
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Laass MW, Schmitz R, Uhlig HH, Zimmer KP, Thamm M, Koletzko S. The prevalence of celiac disease in children and adolescents in Germany. DEUTSCHES ARZTEBLATT INTERNATIONAL 2016; 112:553-60. [PMID: 26356552 DOI: 10.3238/arztebl.2015.0553] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 07/02/2015] [Accepted: 07/02/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND Untreated celiac disease is associated with increased morbidity and mortality. Until now, no up-to-date figures have been available on the prevalence of celiac disease among children and adolescents in Germany, or on the percentage of undiagnosed cases. METHODS To estimate the prevalence of celiac disease, serum samples obtained from 2003 to 2006 from participants in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were studied for celiac disease-specific autoantibodies and total IgA. RESULTS Of the 12 741 study participants aged 1 to 17 years (6546 boys, 6195 girls), 9 (0.07%) had a reported history of celiac disease. An elevated concentration of serum autoantibodies to tissue transglutaminase was found in 91 children with a normal IgA concentration and in 7 with IgA deficiency. The prevalence of undiagnosed celiac disease, based on positive autoantibody findings, was 0.8% (95% confidence interval 0.6-1.0%), and the overall prevalence of the disease was 0.9%. Seropositive children and adolescents had lower ferritin and red blood cell folate concentrations than seronegative ones; they also tended to be shorter and to weigh less as reflected by age- and sex-standardized z-scores. CONCLUSION The 0.9% prevalence of celiac disease in Germany, as determined from a combination of serological findings and clinical histories, is similar to reported prevalences elsewhere in Europe and North America. Pediatricians, primary care physicians, internists, and other specialists should be aware of the broad spectrum of clinical manifestations of this disease. Children who have symptoms suggestive of celiac disease or belong to a group at risk for it should be tested for antibodies against tissue transglutaminase, as should symptomatic adults after the exclusion of other possible causes. It is not yet clear whether asymptomatic adults from high-risk groups should be tested.
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Affiliation(s)
- Martin W Laass
- Institute and Outpatient Clinics of Pediatric and Adolescent Medicine, University Hospital Carl Gustav Carus, Dresden, Department of Epidemiology and Health Monitoring of the Robert Koch Institute, Berlin, Translational Gastroenterology Unit and Department of Pediatrics, John Radcliffe Hospital, Oxford, United Kingdom, Department of General Pediatrics and Neonatology, Center for Pediatric and Adolescent Care, Justus Liebig University, Gießen, Epidemiology Laboratory, Department of Epidemiology and Health Monitoring of the Robert Koch Institute, Berlin, Dr von Hauner Children's Hospital, Campus Innenstadt, Ludwig-Maximilians-Universität München
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Abstract
The paper presents a variety of clinical manifestations of malabsorption syndrome (MAS) in celiac disease, collagenous sprue, Whipple's disease, Crohn's disease, intestinal lymphangiectasia, amyloidosis, common variable immune deficiency, and treatment of short bowel syndrome. It shows the specific features of the pathophysiology, diagnosis, and treatment of MAS in small bowel diseases.
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Affiliation(s)
- A I Parfenov
- Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - L M Krums
- Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
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Rana SS, Dambalkar A, Chhabra P, Sharma R, Nada R, Sharma V, Rana S, Bhasin DK. Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma? Ann Gastroenterol 2016; 29:363-366. [PMID: 27366039 PMCID: PMC4923824 DOI: 10.20524/aog.2016.0042] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 04/20/2016] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Although exocrine pancreatic insufficiency (EPI) has been reported in a number of patients with celiac disease (CD), it is not clear if this is primarily a functional or a structural defect. We studied pancreatic structural abnormalities by endoscopic ultrasound (EUS) in adult CD patients with EPI. METHODS Pancreatic exocrine function was prospectively assessed in 36 recently diagnosed CD patients (mean age: 29.8 years) by measuring fecal elastase. Pancreatic structural changes were assessed in CD patients with EPI by EUS and elastography. Exocrine functions were reassessed after 3 months of gluten-free diet. RESULTS Of the 36 CD patients included, 30 (83%) had anemia, 21 (58%) diarrhea, and 7 (19%) hypothyroidism. Ten (28%) patients had EPI with mean elastase levels of 141.6 μg/g of stool, of whom only one had a history of recurrent acute pancreatitis while the rest 9 patients had no history of acute or chronic pancreatitis. Of these 10 patients, 8 (80%) had diarrhea, 8 (80%) anemia, and 2 (20%) hypothyroidism. EUS was done in 8 patients which showed: normal pancreas in 5 (50%), hyperechoic strands in 3 (30%), and hyperechoic foci without shadowing in 2 (20%) patients. None had lobularity or parenchymal calcification. All patients except the patient with recurrent pancreatitis had normal strain ratio. Follow-up fecal elastase was within normal range in 6 of 7 (86%) patients. CONCLUSION EPI, assessed by fecal elastase levels in adult CD patients, possibly does not relate to structural alterations in the pancreatic parenchyma and may be reversible by following a gluten-free diet.
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Affiliation(s)
- Surinder S. Rana
- Department of Gastroenterology (Surinder S. Rana, Arvind Dambalkar, Puneet Chhabra, Ravi Sharma, Vishal Sharma, Satyavati Rana, Deepak K. Bhasin), Chandigarh, India
| | - Arvind Dambalkar
- Department of Gastroenterology (Surinder S. Rana, Arvind Dambalkar, Puneet Chhabra, Ravi Sharma, Vishal Sharma, Satyavati Rana, Deepak K. Bhasin), Chandigarh, India
| | - Puneet Chhabra
- Department of Gastroenterology (Surinder S. Rana, Arvind Dambalkar, Puneet Chhabra, Ravi Sharma, Vishal Sharma, Satyavati Rana, Deepak K. Bhasin), Chandigarh, India
| | - Ravi Sharma
- Department of Gastroenterology (Surinder S. Rana, Arvind Dambalkar, Puneet Chhabra, Ravi Sharma, Vishal Sharma, Satyavati Rana, Deepak K. Bhasin), Chandigarh, India
| | - Ritambhra Nada
- Department of Histopathology (Ritambhra Nada), Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Vishal Sharma
- Department of Gastroenterology (Surinder S. Rana, Arvind Dambalkar, Puneet Chhabra, Ravi Sharma, Vishal Sharma, Satyavati Rana, Deepak K. Bhasin), Chandigarh, India
| | - Satyavati Rana
- Department of Gastroenterology (Surinder S. Rana, Arvind Dambalkar, Puneet Chhabra, Ravi Sharma, Vishal Sharma, Satyavati Rana, Deepak K. Bhasin), Chandigarh, India
| | - Deepak K. Bhasin
- Department of Gastroenterology (Surinder S. Rana, Arvind Dambalkar, Puneet Chhabra, Ravi Sharma, Vishal Sharma, Satyavati Rana, Deepak K. Bhasin), Chandigarh, India
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17
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Abstract
Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population.
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Affiliation(s)
- Benjamin Lebwohl
- Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA Department of Medical Epidemiology and Biostatistics, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden Department of Pediatrics, Örebro University Hospital, Sweden
| | - Peter H R Green
- Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
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18
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Laass MW, Schmitz R, Uhlig HH, Zimmer KP, Thamm M, Koletzko S. The prevalence of celiac disease in children and adolescents in Germany. DEUTSCHES ARZTEBLATT INTERNATIONAL 2015. [PMID: 26356552 DOI: 10.3238/arztebl.2015.0553.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Untreated celiac disease is associated with increased morbidity and mortality. Until now, no up-to-date figures have been available on the prevalence of celiac disease among children and adolescents in Germany, or on the percentage of undiagnosed cases. METHODS To estimate the prevalence of celiac disease, serum samples obtained from 2003 to 2006 from participants in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were studied for celiac disease-specific autoantibodies and total IgA. RESULTS Of the 12 741 study participants aged 1 to 17 years (6546 boys, 6195 girls), 9 (0.07%) had a reported history of celiac disease. An elevated concentration of serum autoantibodies to tissue transglutaminase was found in 91 children with a normal IgA concentration and in 7 with IgA deficiency. The prevalence of undiagnosed celiac disease, based on positive autoantibody findings, was 0.8% (95% confidence interval 0.6-1.0%), and the overall prevalence of the disease was 0.9%. Seropositive children and adolescents had lower ferritin and red blood cell folate concentrations than seronegative ones; they also tended to be shorter and to weigh less as reflected by age- and sex-standardized z-scores. CONCLUSION The 0.9% prevalence of celiac disease in Germany, as determined from a combination of serological findings and clinical histories, is similar to reported prevalences elsewhere in Europe and North America. Pediatricians, primary care physicians, internists, and other specialists should be aware of the broad spectrum of clinical manifestations of this disease. Children who have symptoms suggestive of celiac disease or belong to a group at risk for it should be tested for antibodies against tissue transglutaminase, as should symptomatic adults after the exclusion of other possible causes. It is not yet clear whether asymptomatic adults from high-risk groups should be tested.
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Affiliation(s)
- Martin W Laass
- Institute and Outpatient Clinics of Pediatric and Adolescent Medicine, University Hospital Carl Gustav Carus, Dresden, Department of Epidemiology and Health Monitoring of the Robert Koch Institute, Berlin, Translational Gastroenterology Unit and Department of Pediatrics, John Radcliffe Hospital, Oxford, United Kingdom, Department of General Pediatrics and Neonatology, Center for Pediatric and Adolescent Care, Justus Liebig University, Gießen, Epidemiology Laboratory, Department of Epidemiology and Health Monitoring of the Robert Koch Institute, Berlin, Dr von Hauner Children's Hospital, Campus Innenstadt, Ludwig-Maximilians-Universität München
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Laass MW, Röber N, Range U, Noß L, Roggenbuck D, Conrad K. Loss and Gain of Tolerance to Pancreatic Glycoprotein 2 in Celiac Disease. PLoS One 2015; 10:e0128104. [PMID: 26047356 PMCID: PMC4457647 DOI: 10.1371/journal.pone.0128104] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Accepted: 04/23/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Autoantibodies against pancreatic secretory-granule membrane glycoprotein 2 (GP2) have been demonstrated in patients with Crohn's disease but recently also with celiac disease (CD). Both entities are characterized by intestinal barrier impairment with increased gut permeability. Pathophysiological hallmark of CD is a permanent loss of tolerance to alimentary gliadin and a transient loss of tolerance to the autoantigen human tissue transglutaminase (tTG). Therefore, we explored the behavior of loss of tolerance to GP2 reported in CD. METHODS We assessed prevalences and levels of autoantibodies against GP2, CD-specific antibodies to endomysial antigens and tTG as well as Crohn's disease-specific anti-Saccharomyces cerevisiae antibodies in sera of 174 patients with active CD, 84 patients under gluten-free diet (GFD) and 129 controls. Furthermore, we looked for an association between anti-GP2 antibody positivity and degree of mucosal damage in CD. RESULTS We found significantly elevated anti-GP2 IgA positivity in active CD patients (19.5%) compared to CD patients under GFD (0.0%) and controls (5.4%, p < 0.001, respectively). Anti-GP2 IgA levels correlated significantly with CD-specific antibodies (p < 0.001). Anti-GP2 autoantibody positivity disappeared under GFD similarly to CD-specific autoantibodies against tTG and endomysial antigens. For the first time, IgA antibody levels to GP2 are demonstrated to be associated with degree of villous atrophy according to Marsh classification. CONCLUSIONS Anti-GP2 IgA seems to be associated with disease activity in a distinct subgroup of patients with CD. The observed loss of tolerance to GP2 in a subset of patients with CD is transient and disappears under GFD.
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Affiliation(s)
- Martin W. Laass
- Children’s Hospital, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
- * E-mail:
| | - Nadja Röber
- Institute of Immunology, Technische Universität Dresden, 01307 Dresden, Germany
| | - Ursula Range
- Institute for Medical Informatics and Biometry, Technische Universität Dresden, 01307 Dresden, Germany
| | - Lydia Noß
- Children’s Hospital, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | - Dirk Roggenbuck
- GA Generic Assays GmbH, 15827 Dahlewitz/Berlin, Germany
- Faculty of Science, Brandenburg University of Technology Cottbus-Senftenberg, 01968 Senftenberg, Germany
| | - Karsten Conrad
- Institute of Immunology, Technische Universität Dresden, 01307 Dresden, Germany
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Mattar R, Lima GAS, da Costa MZG, Silva-Etto JMK, Guarita D, Carrilho FJ. Comparison of fecal elastase 1 for exocrine pancreatic insufficiency evaluation between ex-alcoholics and chronic pancreatitis patients. ARQUIVOS DE GASTROENTEROLOGIA 2015; 51:297-301. [PMID: 25591157 DOI: 10.1590/s0004-28032014000400006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 05/05/2014] [Accepted: 07/07/2014] [Indexed: 01/26/2023]
Abstract
CONTEXT Fecal elastase is a noninvasive test for pancreatic insufficiency diagnosis. OBJECTIVES Evaluate the usefulness of fecal elastase 1 for the indication of exocrine pancreatic insufficiency among former alcohol addicts and patients with chronic pancreatitis. METHODS Forty-three patients with chronic pancreatitis and thirty-three asymptomatic former alcohol addicts entered the study. The levels of fecal elastase 1 were measured using a commercial kit. Pancreatic imaging findings were used to categorize the groups. RESULTS The levels of fecal elastase 1 were significantly lower in the patients than in the former alcohol addicts and in the group with tissue calcifications, duct alterations, or atrophy. With a cutoff level of 100 μg/g, the sensitivity of fecal elastase 1 in chronic pancreatitis was 46.51% and its specificity was 87.88% with a positive predictive value of 83.33% and a negative predictive value of 55.77%. When patients were stratified according to the severity of their pancreatitis, the sensitivity was 6.25% for mild pancreatitis and 70.37% for marked pancreatitis. CONCLUSION Low level of fecal elastase 1 was associated with marked rather than mild chronic pancreatitis; however, it may be useful to indicate pancreatic exocrine insufficiency in asymptomatic former alcohol addicts.
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Affiliation(s)
- Rejane Mattar
- Divisão de Gastroenterologia e Hepatologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil
| | - Gustavo André Silva Lima
- Divisão de Gastroenterologia e Hepatologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil
| | - Marianges Zadrozny Gouvêa da Costa
- Divisão de Gastroenterologia e Hepatologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil
| | - Joyce M Kinoshita Silva-Etto
- Divisão de Gastroenterologia e Hepatologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil
| | - Dulce Guarita
- Divisão de Gastroenterologia e Hepatologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil
| | - Flair José Carrilho
- Divisão de Gastroenterologia e Hepatologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brasil
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Bhutia SC, Singh TA, Sherpa ML. Production of a polyclonal antibody against osteogenic protein-1, and its role in the diagnosis of osteoarthritis. Singapore Med J 2014; 55:388-91. [PMID: 25091889 DOI: 10.11622/smedj.2014092] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
INTRODUCTION Osteoarthritis (OA) is a progressive degenerative disorder of the articular cartilage. Available diagnostic radiography has been poorly associated with the progress and severity of this clinical disease. As osteogenic protein-1 (OP-1) has been identified as a bone morphogenetic protein with a major role in cartilage repair, we aimed to evaluate its potential role in the diagnosis of OA. METHODS This was an experimental study conducted at the Department of Biochemistry, Sikkim Manipal Institute of Medical Sciences, India. Polyclonal antibodies (i.e. anti-OP-1[f]) were raised against OP-1 in mice, and subsequently used in a sandwich enzyme-linked immunosorbent assay (ELISA) to detect the presence of OP-1 in the synovial fluids of 75 osteoarthritic patients. For the purpose of correlation, the radiographic assessments of the knees of the 75 patients were graded using the Kellgren-Lawrence scoring system. RESULT The polyclonal antibody (i.e. anti-OP-1[f]) raised against OP-1 was able to detect the presence of OP-1 in the synovial fluids of all the osteoarthritic patients via sandwich ELISA. The level of the OP-1 was found to be much higher than the reference range and correlated positively with the severity of OA (r = 0.24; p = 0.04). CONCLUSION Our study shows that the polyclonal antibody, anti OP-1(f), could be used for the immunodiagnosis of osteoarthritis via sandwich ELISA.
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Affiliation(s)
| | | | - Mingma Lhamu Sherpa
- Department of Biochemistry, Sikkim Manipal Institute of Medical Sciences, Gangtok 737102, Sikkim, India.
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Suárez Llanos JP, González Melo E, Mora Mendoza A, Iacampo Leiva LD, Moro Miguel MA. Celiac disease and malabsorption: a case report of ataxia secondary to vitamin E deficiency. ENDOCRINOLOGIA Y NUTRICION : ORGANO DE LA SOCIEDAD ESPANOLA DE ENDOCRINOLOGIA Y NUTRICION 2014; 61:389-390. [PMID: 24840130 DOI: 10.1016/j.endonu.2014.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2013] [Revised: 03/27/2014] [Accepted: 03/28/2014] [Indexed: 06/03/2023]
Affiliation(s)
- José Pablo Suárez Llanos
- Servicio de Endocrinología y Nutrición, Hospital Universitario de Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, España.
| | - Estefanía González Melo
- Servicio de Endocrinología y Nutrición, Hospital Universitario de Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, España
| | - Alejandra Mora Mendoza
- Servicio de Endocrinología y Nutrición, Hospital Universitario de Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, España
| | - Lucas Dario Iacampo Leiva
- Servicio de Neurología, Hospital Universitario de Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, España
| | - María Adoración Moro Miguel
- Servicio de Neurología, Hospital Universitario de Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, España
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Early spontaneous recovery of exocrine pancreatic insufficiency in a 3-year-old child with Shwachman-Diamond syndrome. Indian J Gastroenterol 2014; 33:295-6. [PMID: 24052373 DOI: 10.1007/s12664-013-0388-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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Pezzilli R, Andriulli A, Bassi C, Balzano G, Cantore M, Fave GD, Falconi M, Group LFTEPIC(EPI. Exocrine pancreatic insufficiency in adults: A shared position statement of the Italian association for the study of the pancreas. World J Gastroenterol 2013; 19:7930-7946. [PMID: 24307787 PMCID: PMC3848141 DOI: 10.3748/wjg.v19.i44.7930] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Revised: 08/18/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas (AISP). We covered the main diseases associated with exocrine pancreatic insufficiency (EPI) which are of common interest to internists/gastroenterologists, oncologists and surgeons, fully aware that EPI may also occur together with many other diseases, but less frequently. A preliminary manuscript based on an extended literature search (Medline/PubMed, Cochrane Library and Google Scholar) of published reports was prepared, and key recommendations were proposed. The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012. Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached. The final draft of the manuscript was then sent to the AISP Council for approval and/or modification. All concerned parties approved the final version of the manuscript in June 2013.
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Fuhrmann G, Leroux JC. Improving the stability and activity of oral therapeutic enzymes-recent advances and perspectives. Pharm Res 2013; 31:1099-105. [PMID: 24185592 DOI: 10.1007/s11095-013-1233-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Accepted: 10/14/2013] [Indexed: 12/19/2022]
Abstract
Exogenous, orally-administered enzymes are currently in clinical use or under development for the treatment of pathologies, such as celiac disease and phenylketonuria. However, the administration of therapeutic enzymes via the oral route remains challenging due to potential inactivation of these fragile macromolecular entities in the harsh environment of the gastrointestinal tract. Enzymes are particularly sensitive because both proteolysis and unfolding can lead to their inactivation. Current efforts to overcome these shortcomings involve the application of gastro-resistant delivery systems and the modification of enzyme structures by polymer conjugation or protein engineering. This perspective manuscript reviews and critically discusses recent progress in the oral delivery of therapeutic enzymes, whose substrate is localized in the gastrointestinal tract.
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Affiliation(s)
- Gregor Fuhrmann
- Institute of Pharmaceutical Sciences Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Pauli-Str. 10, HCI H 301, 8093, Zurich, Switzerland
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Sadr-Azodi O, Sanders DS, Murray JA, Ludvigsson JF. Patients with celiac disease have an increased risk for pancreatitis. Clin Gastroenterol Hepatol 2012; 10:1136-1142.e3. [PMID: 22801059 PMCID: PMC3494459 DOI: 10.1016/j.cgh.2012.06.023] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Revised: 06/05/2012] [Accepted: 06/18/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with celiac disease have been reported to be at increased risk for pancreatitis and pancreatic insufficiency, but the risk might have been overestimated because of patient selection and limited numbers of patients for analysis. Furthermore, no distinction has been made between patients with gallstone-related and non-gallstone-related pancreatitis. We performed a nationwide study to determine the risk for any pancreatitis or subtype of pancreatitis among patients with biopsy-verified celiac disease. METHODS We analyzed data from patients in Sweden with celiac disease (n = 28,908) who were identified on the basis of small intestinal biopsy records from 28 pathology departments (those with villous atrophy, Marsh 3). Biopsies were performed from 1969 to 2008, and biopsy report data were collected from 2006 to 2008. Patients with pancreatitis were identified on the basis of diagnostic codes in the Swedish Patient Register and records of pancreatic enzyme use in the Swedish Prescribed Drug Register. Data were matched with those from 143,746 individuals in the general population; Cox regression was used to estimate hazard ratios (HRs) for pancreatitis. RESULTS We identified 406 patients with celiac disease who were later diagnosed with pancreatitis (and 143 with expected pancreatitis) (HR, 2.85; 95% confidence interval [CI], 2.53-3.21). The absolute risk of any pancreatitis among patients with celiac disease was 126/100,000 person-years, with an excess risk of 81/100,000 person-years. The HR for gallstone-related acute pancreatitis was 1.59 (95% CI, 1.06-2.40), for non-gallstone-related acute pancreatitis HR was 1.86 (95% CI, 1.52-2.26), for chronic pancreatitis HR was 3.33 (95% CI, 2.33-4.76), and for supplementation with pancreatic enzymes HR was 5.34 (95% CI, 2.99-9.53). The risk of any pancreatitis within 5 years of diagnosis was 2.76 (95% CI, 2.36-3.22). CONCLUSIONS Based on an analysis of medical records from Sweden, patients with celiac disease have an almost 3-fold increase in risk of developing pancreatitis, compared with the general population.
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Affiliation(s)
- Omid Sadr-Azodi
- Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - David S. Sanders
- Gastroenterology and Liver Unit, Royal Hallamshire Hospital & University of Sheffield, Sheffield, UK
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Departments of Medicine and Immunology, Mayo Clinic College of Medicine, Rochester, USA
| | - Jonas F Ludvigsson
- Division of Gastroenterology and Hepatology, Departments of Medicine and Immunology, Mayo Clinic College of Medicine, Rochester, USA
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
- Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Sweden
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Nakajima K, Oshida H, Muneyuki T, Kakei M. Pancrelipase: an evidence-based review of its use for treating pancreatic exocrine insufficiency. CORE EVIDENCE 2012; 7:77-91. [PMID: 22936895 PMCID: PMC3426252 DOI: 10.2147/ce.s26705] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pancreatic exocrine insufficiency (PEI) is often observed in patients with pancreatic diseases, including chronic pancreatitis, cystic fibrosis, and tumors, or after surgical resection. PEI often results in malnutrition, weight loss and steatorrhea, which together increase the risk of morbidity and mortality. Therefore, nutritional interventions, such as low-fat diets and pancreatic enzyme replacement therapy (PERT), are needed to improve the clinical symptoms, and to address the pathophysiology of pancreatic exocrine insufficiency. PERT with delayed-release pancrelipase is now becoming a standard therapy for pancreatic exocrine insufficiency because it significantly improves the coefficients of fat and nitrogen absorption as well as clinical symptoms, without serious treatment-emergent adverse events. The major adverse events were tolerable gastrointestinal tract symptoms, such as stomach pain, nausea, and bloating. Fibrosing colonopathy, a serious complication, is associated with high doses of enzymes. Several pancrelipase products have been approved by the US Food and Drug Administration in recent years. Although many double-blind, placebo-controlled trials of pancrelipase products have been conducted in recent years, these studies have enrolled relatively few patients and have often been less than a few weeks in duration. Moreover, few studies have addressed the issue of pancreatic diabetes, a type of diabetes that is characterized by frequent hypoglycemia, which is difficult to manage. In addition, it is unclear whether PERT improves morbidity and mortality in such settings. Therefore, large, long-term prospective studies are needed to identify the optimal treatment for pancreatic exocrine insufficiency. The studies should also examine the extent to which PERT using pancrelipase improves mortality and morbidity. The etiology and severity of pancreatic exocrine insufficiency often differ among patients with gastrointestinal diseases or diabetes (type 1 and type 2), and among elderly subjects. Finally, although there is currently limited clinical evidence, numerous extrapancreatic diseases and conditions that are highly prevalent in the general population may also be considered potential targets for PERT and related treatments.
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Affiliation(s)
- Kei Nakajima
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado
| | - Haruki Oshida
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado
| | - Toshitaka Muneyuki
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, Amanuma, Omiya, Saitama, Japan
| | - Masafumi Kakei
- First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, Amanuma, Omiya, Saitama, Japan
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Pitchumoni CS, Pitchumoni CS, Pitchumoni CS, Chen N. Celiac Disease. GERIATRIC GASTROENTEROLOGY 2012:501-510. [DOI: 10.1007/978-1-4419-1623-5_52] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Abstract
Exocrine pancreatic disease is thought to be uncommon in clinical practice and usually secondary to excess alcohol intake. Although excess alcohol intake does account for many cases of exocrine pancreatic disease, other conditions are associated with exocrine pancreatic insufficiency and such dysfunction perhaps occurs more frequently than conventionally expected. A reliable, patient-friendly, cheap and easy to use test for exocrine pancreatic disease is yet to be established; however, in many countries the main (and often only available) method of assessment of exocrine pancreatic function is the fecal-elastase-1 test. This Review examines the role of fecal-elastase-1 testing in detecting exocrine pancreatic insufficiency in a number of gastrointestinal and nongastrointestinal conditions and determines the value of pancreatic enzyme supplementation in these settings.
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