REVIEW ARTICLE
Exocrine pancreatic insufficiency in systemic diseases: unravelling the complex interplay – a comprehensive review
 
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1
Dow University of Health Sciences, Sindh, Pakistan
 
2
Liaquat National Hospital and Medical College, Karachi, Pakistan
 
3
Baqai Medical College, Karachi, Pakistan
 
4
Allama Iqbal Medical College, Lahore, Pakistan
 
5
Medical College Baroda, Gujarat, India
 
6
Jinnah Sindh Medical University, Karachi, Pakistan
 
 
Submission date: 2024-02-04
 
 
Acceptance date: 2024-04-07
 
 
Publication date: 2024-07-07
 
 
Corresponding author
Muhammad Ali Muzammil
Dow University of Health Sciences Sindh, Pakistan
 
 
Pol J Pathol 2024;75(2):65-76
 
KEYWORDS
TOPICS
ABSTRACT
Exocrine pancreatic insufficiency (EPI) is characterised by the pancreas’s inadequate synthesis or release of digestive enzymes, which impairs digestion and causes nutritional malabsorption. To effectively manage concomitant systemic disorders and provide personalised therapy, early identification is essential. The production of digestive enzymes is a key component in the processes of EPI, which is linked to several conditions such as pancreatic cancer, cystic fibrosis, chronic pancreatitis, and diabetes-related fibrosis. Other causes include aging, smoking, inflammatory bowel disease (IBD), and stomach removal. Exocrine pancreatic insufficiency causes prolonged diarrhoea in celiac disease, perhaps resulting in pancreatitis and autoimmune processes. With mechanisms involving inflammation, bile duct scarring, pancreatic autoantibodies, and extraintestinal manifestations, EPI prevalence in IBD is noteworthy. Both indirect and direct tests are used in the diagnosis of EPI, and secretin-induced magnetic resonance cholangiopancreatography imaging provides a thorough evaluation. Modifications to lifestyle, therapy modalities such as pancreatic enzyme replacement therapy, and innovative therapies for genetic disorders are all part of the management. Pancreatic enzyme replacement treatment is important because micronutrient deficits, including calcium, magnesium, zinc, and vitamins, are present in EPI patients.
Innovative treatments investigate machine learning and PARP enzymes for prophylactic and diagnostic purposes, advancing more accurate EPI diagnosis and treatment in systemic disorders.
REFERENCES (67)
1.
Kunovský L, Dítě P, Jabandžiev P, et al. Causes of exocrine pancreatic insufficiency other than chronic pancreatitis. J Clin Med 2021; 10: 5779.
 
2.
Forsmark CE. Diagnosis and management of exocrine pancreatic insufficiency. Curr Treat Options Gastroenterol 2018; 16: 306-315.
 
3.
Huang W, de la Iglesia-García D, Baston-Rey I, et al. Exocrine pancreatic insufficiency following acute pancreatitis: systematic review and meta-analysis. Dig Dis Sci 2019; 64: 1985-2005.
 
4.
Nikfarjam M, Wilson JS, Smith RC, et al. Diagnosis and management of pancreatic exocrine insufficiency. Med J Aust 2017; 207: 161-165.
 
5.
Karpińska M, Czauderna M. Pancreas – its functions, disorders, and physiological impact on the mammals’ organism. Front Physiol 2022; 13: 807632.
 
6.
Löhr JM, Dominguez-Munoz E, Rosendahl J, et al. United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU). United European Gastroenterol J 2017; 5: 153-199.
 
7.
Machicado JD, Chari ST, Timmons L, Tang G, Yadav D. A population-based evaluation of the natural history of chronic pancreatitis. Pancreatology 2018; 18: 39-45.
 
8.
Hollemans RA, Hallensleben NDL, Mager DJ, et al. Pancreatic exocrine insufficiency following acute pancreatitis: systematic review and study level meta-analysis. Pancreatology 2018; 18: 253-262.
 
9.
Pezzilli R, Zerbi A, Campra D, et al. Consensus guidelines on severe acute pancreatitis. Dig Liver Dis 2015; 47: 532-543.
 
10.
Vujasinovic M, Valente R, Maier P, et al. Diagnosis, treatment and long-term outcome of autoimmune pancreatitis in Sweden. Pancreatology 2018; 18: 900-904.
 
11.
Sikkens EC, Cahen DL, de Wit J, Looman CW, van Eijck C, Bruno MJ. A prospective assessment of the natural course of the exocrine pancreatic function in patients with a pancreatic head tumor. J Clin Gastroenterol 2014; 48: e43-46.
 
12.
Singh VK, Schwarzenberg SJ. Pancreatic insufficiency in cystic fibrosis. J Cyst Fibros 2017; 16: S70-S78.
 
13.
Ikuse T, Kudo T, Arai K, et al. Shwachman-Diamond syndrome: nationwide survey and systematic review in Japan. Pediatr Int 2018; 60: 719-726.
 
14.
Mohapatra S, Majumder S, Smyrk TC, et al. Diabetes mellitus is associated with an exocrine pancreatopathy: conclusions from a review of literature. Pancreas 2016; 45: 104-110.
 
15.
Piciucchi M, Capurso G, Archibugi L, Delle Fave MM, Capasso M, Delle Fave G. Exocrine pancreatic insufficiency in diabetic patients: prevalence, mechanisms, and treatment. Int J Endocrinol 2015; 2015: 595649.
 
16.
Maconi G, Dominici R, Molteni M, et al. Prevalence of pancreatic insufficiency in inflammatory bowel diseases. Assessment by fecal elastase-1. Dig Dis Sci 2008; 53: 262-270.
 
17.
Antonini F, Crippa S, Falconi M, Macarri G, Pezzilli R. Pancreatic enzyme replacement therapy after gastric resection: an update. Dig Liver Dis 2018; 50: 1-5.
 
18.
Löhr JM, Panic N, Vujasinovic M, Verbeke CS. The aging pancreas: a systematic review of the evidence and analysis of the consequences. J Intern Med 2018; 283: 446-460.
 
19.
Bülow R, Simon P, Thiel R, et al. Anatomic variants of the pancreatic duct and their clinical relevance: an MR-guided study in the general population. Eur Radiol 2014; 24: 3142-3149.
 
20.
Raphael KL, Chawla S, Kim S, et al. Pancreatic insufficiency secondary to tobacco exposure: a controlled cross-sectional evaluation. Pancreas 2017; 46: 237-243.
 
21.
Cooney AL, McCray PB Jr, Sinn PL. Cystic fibrosis gene therapy: looking back, looking forward. Genes (Basel) 2018; 9: 538.
 
22.
Nousia-Arvanitakis S, Fotoulaki M, Tendzidou K, Vassilaki C, Agguridaki C, Karamouzis M. Subclinical exocrine pancreatic dysfunction resulting from decreased cholecystokinin secretion in the presence of intestinal villous atrophy. J Pediatr Gastroenterol Nutr 2006; 43: 307-312.
 
23.
Zsóri G, Illés D, Terzin V, Ivány E, Czakó L. Exocrine pancreatic insufficiency in type 1 and type 2 diabetes mellitus: do we need to treat it? A systematic review. Pancreatology 2018; 18: 559-565.
 
24.
Hayden MR, Karuparthi PR, Habibi J, et al. Ultrastructure of islet microcirculation, pericytes, and the islet exocrine interface in the HIP rat model of diabetes. Exp Biol Med (Maywood) 2008; 233: 1109-1123.
 
25.
Begovatz P, Koliaki C, Weber K, et al. Pancreatic adipose tissue infiltration, parenchymal steatosis and beta cell function in humans. Diabetologia 2015; 58: 1646-1655.
 
26.
Rodriguez-Calvo T, Ekwall O, Amirian N, Zapardiel-Gonzalo J, von Herrath MG. Increased immune cell infiltration of the exocrine pancreas: a possible contribution to the pathogenesis of type 1 diabetes. Diabetes 2014; 63: 3880-3890.
 
27.
Dominguez-Mu¼oz JE. Management of pancreatic exocrine insufficiency. Curr Opin Gastroenterol 2019; 35: 455-459.
 
28.
Hammer HF. Pancreatic exocrine insufficiency: diagnostic evaluation and replacement therapy with pancreatic enzymes. Dig Dis 2010; 28: 339-343.
 
29.
Knop FK, Vilsbøll T, Larsen S, et al. Increased postprandial responses of GLP-1 and GIP in patients with chronic pancreatitis and steatorrhea following pancreatic enzyme substitution. Am J Physiol Endocrinol Metab 2007; 292: E324-330.
 
30.
Ewald N, Bretzel RG, Fantus IG, et al. Pancreatin therapy in patients with insulin-treated diabetes mellitus and exocrine pancreatic insufficiency according to low fecal elastase 1 concentration. Results of a prospective multi-center trial. Diabetes Metab Res Rev 2007; 23: 386-391.
 
31.
Dreiling DA. The pancreatic secretion in the malabsorption syndrome and related malnutrition states. J Mt Sinai Hosp N Y 1957; 24: 243-50.
 
32.
Abdulkarim AS, Burgart LJ, See J, Murray JA. Etiology of nonresponsive celiac disease: results of a systematic approach. Am J Gastroenterol 2002; 97: 2016-2021.
 
33.
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.
 
34.
Sasamori H, Fukui T, Hayashi T, et al. Analysis of pancreatic volume in acute-onset, slowly-progressive and fulminant type 1 diabetes in a Japanese population. J Diabetes Investig 2018; 9: 1091-1099.
 
35.
Licul V, Cizmarević NS, Ristić S, Mikolasević I, Mijandrusić BS. CTLA-4 +49 and TNF-αlpha-308 gene polymorphisms in celiac patients with exocrine pancreatic insufficiency. Coll Antropol 2013; 37: 1191-1194.
 
36.
Pezzilli R, Andriulli A, Bassi C, et al. 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.
 
37.
Yoosuf S, Barrett CG, Papamichael K, et al. Pancreatic enzyme supplementation versus placebo for improvement of gastrointestinal symptoms in non-responsive celiac disease: a cross-over randomized controlled trial. Front Med (Lausanne) 2023; 9: 1001879.
 
38.
Evans KE, Leeds JS, Morley S, Sanders DS. Pancreatic insufficiency in adult celiac disease: do patients require long-term enzyme supplementation? Dig Dis Sci 2010; 55: 2999-3004.
 
39.
Spanier BW, Dijkgraaf MG, Bruno MJ. Epidemiology, etiology, and outcome of acute and chronic pancreatitis: an update. Best Pract Res Clin Gastroenterol 2008; 22: 45-63.
 
40.
Soubières AA, Poullis A. Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease. World J Gastrointest Pharmacol Ther 2016; 7: 41-50.
 
41.
Joossens S, Vermeire S, van Steen K, et al. Pancreatic autoantibodies in inflammatory bowel disease. Inflamm Bowel Dis 2004; 10: 771-777.
 
42.
Bogdanos DP, Rigopoulou EI, Smyk DS, et al. Diagnostic value, clinical utility and pathogenic significance of reactivity to the molecular targets of Crohn’s disease specific-pancreatic autoantibodies. Autoimmun Rev 2011; 11: 143-148.
 
43.
Fousekis FS, Theopistos VI, Katsanos KH, Christodoulou DK. Pancreatic involvement in inflammatory bowel disease: a review. J Clin Med Res 2018; 10: 743-751.
 
44.
Pham A, Forsmark C. Chronic pancreatitis: review and update of etiology, risk factors, and management. F1000Res 2018; 7: F1000 Faculty Rev-607.
 
45.
Fine KD, Ogunji F. A new method of quantitative fecal fat microscopy and its correlation with chemically measured fecal fat output. Am J Clin Pathol 2000; 113: 528-534.
 
46.
Löser C, Möllgaard A, Fölsch UR. Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test. Gut 1996; 39: 580-586.
 
47.
Couper RT, Corey M, Durie PR, Forstner GG, Moore DJ. Longitudinal evaluation of serum trypsinogen measurement in pancreatic-insufficient and pancreatic-sufficient patients with cystic fibrosis. J Pediatr 1995; 127: 408-413.
 
48.
Perbtani Y, Forsmark CE. Update on the diagnosis and management of exocrine pancreatic insufficiency. F1000Res 2019; 8:F1000 Faculty Rev-1991.
 
49.
Lembcke B, Braden B, Caspary WF. Exocrine pancreatic insufficiency: accuracy and clinical value of the uniformly labelled 13C-Hiolein breath test. Gut 1996; 39: 668-674.
 
50.
Domínguez-Mu¼oz JE, Nieto L, Vilari¼o M, Lourido MV, Iglesias-García J. Development and diagnostic accuracy of a breath test for pancreatic exocrine insufficiency in chronic pancreatitis. Pancreas 2016; 45: 241-247.
 
51.
Dreiling DA. Pancreatic secretory testing in 1974. Gut 1975; 16: 653-657.
 
52.
Mee AS, Girdwood AH, Walker E, Gilinsky NH, Kottler RE, Marks IN. Comparison of the oral (PABA) pancreatic function test, the secretin-pancreozymin test and endoscopic retrograde pancreatography in chronic alcohol induced pancreatitis. Gut 1985; 26: 1257-1262.
 
53.
Othman MO, Harb D, Barkin JA. Introduction and practical approach to exocrine pancreatic insufficiency for the practicing clinician. Int J Clin Pract 2018; 72: e13066.
 
54.
Albashir S, Bronner MP, Parsi MA, Walsh RM, Stevens T. Endoscopic ultrasound, secretin endoscopic pancreatic function test, and histology: correlation in chronic pancreatitis. Am J Gastroenterol 2010; 105: 2498-2503.
 
55.
Singh VK, Yadav D, Garg PK. Diagnosis and management of chronic pancreatitis: a review. JAMA 2019; 322: 2422-2434.
 
56.
Frøkjºr JB, Akisik F, Farooq A, et al. Consensus guidelines for chronic pancreatitis. guidelines for the diagnostic cross sectional imaging and severity scoring of chronic pancreatitis. Pancreatology 2018; 18: 764-773.
 
57.
Schneider AR, Hammerstingl R, Heller M, et al. Does secretin- stimulated MRCP predict exocrine pancreatic insufficiency? A comparison with noninvasive exocrine pancreatic function tests. J Clin Gastroenterol 2006; 40: 851-855.
 
58.
Enzimi digestivi: che cosa sono e perché prenderli? Available from: https://www.supersmart.com/it/....
 
59.
Domínguez-Mu¼oz JE. Pancreatic exocrine insufficiency: diagnosis and treatment. J Gastroenterol Hepatol 2011; 26: 12-16.
 
60.
Trang T, Chan J, Graham DY. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century. World J Gastroenterol 2014; 20: 11467-11485.
 
61.
Sikkens EC, Cahen DL, Koch AD, et al. The prevalence of fat-soluble vitamin deficiencies and a decreased bone mass in patients with chronic pancreatitis. Pancreatology 2013; 13: 238-242.
 
62.
Clancy JP, Cotton CU, Donaldson SH, et al. CFTR modulator theratyping: current status, gaps and future directions. J Cyst Fibros 2019; 18: 22-34.
 
63.
Diéguez-Castillo C, Jiménez-Luna C, Prados J, Martín-Ruiz JL, Caba O. State of the art in exocrine pancreatic insufficiency. Medicina (Kaunas) 2020; 56: 523.
 
64.
Alkaade S, Vareedayah AA. A primer on exocrine pancreatic insufficiency, fat malabsorption, and fatty acid abnormalities. Am J Manag Care 2017; 23: S203-S209.
 
65.
Hart PA, Conwell DL. Challenges and updates in the management of exocrine pancreatic insufficiency. Pancreas 2016; 45: 1-4.
 
66.
Martínez-Bosch N, Fernández-Zapico ME, Navarro P, Yéla- mos J. Poly(ADP-Ribose) polymerases: new players in the pathogenesis of exocrine pancreatic diseases. Am J Pathol 2016; 186: 234-241.
 
67.
Pyenson B, Alston M, Gomberg J, et al. Applying machine learning techniques to identify undiagnosed patients with exocrine pancreatic insufficiency. J Health Econ Outcomes Res 2019; 6: 32-46.
 
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