Crohn's Disease and Acute Pancreatitis. A Review of Literature
Abstract
Crohn's disease, a transmural inflammatory bowel disease, has many well-known extra-intestinal manifestations and complications. Although acute pancreatitis has a higher incidence in patients with Crohn's disease as compared to the general population, acute pancreatitis is still relatively uncommon in patients with Crohn's disease. Patients with Crohn's disease are at an approximately fourfold higher risk than the general population to develop acute pancreatitis. The risk of developing acute pancreatitis is higher in females as compared to males. Acute pancreatitis can occur at any age with higher incidence reported in patients in their 20s and between 40-50 years of age. The severity and prognosis of acute pancreatitis in patients with Crohn's disease is the same as in general population. Acute pancreatitis can occur before onset of intestinal Crohn's disease, this presentation being more common in children than adults. It can also occur as the presenting symptom. However, most commonly it occurs after intestinal symptoms have manifest with a mean time interval between the initial presentation and development of acute pancreatitis being 2 years. There are several etiological factors contributing to acute pancreatitis in patients with Crohn's disease. It is not clear whether acute pancreatitis is a direct extra-intestinal manifestation of Crohn's disease; however, majority of the cases of acute pancreatitis in patients with Crohn's disease are due to GS and medications. Drugs used for the treatment of Crohn's disease that have been reported to cause acute pancreatitis include 5-ASA agents, azathioprine and 6 mercaptopurine, metornidazole and corticosteroids. Recent evidence has emerged correlating both type 1 and 2 autoimmune pancreatitis with Crohn's disease. Understanding the association between the two disease entities is key to effectively manage patients with Crohn's disease and acute pancreatitis.
Image: Monmouth Medical Center. Long Branch, NJ, USA.
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Lichtenstein GR, Hanauer SB, Sandborn WJ et al. Management of Crohn’ s Disease in Adults. Am J Gastroenterol 2009; 104:465-83. [PMID: 19174807]
Ball WP, Baggenstoss AH, Bargen JA. Pancreatic lesions associated with chronic ulcerative colitis. Arch Pathol (Chic). 1950; 50:347–358. [PMID: 15433704]
Lysy J, Goldin E. Pancreatitis in ulcerative colitis. J Clin Gastroenterol. 1992; 15:336–339.
Forbes D, Scott RB, Trevenen C, et al. Chronic pancreatitis associated with ulcerative colitis. Clin Invest Med. 1987; 10:321–324.
Weber P, Seibold F, Jenss H. Acute pancreatitis in Crohn’s disease. J Clin Gastroenterol 1993; 17:286-291.
Yadav D, Agrawal N, Pitchumoni CS, et al. A critical evaluation of laboratory tests in acute pancreatitis. Am J Gastroenterol 2002; 97:1310-1316. [PMID: 12094843]
Rasmussen HH, Fonager K, Sorensen HT, et al. Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. A Danish 16-year nationwide follow-up study. Scand J Gastroenterol. 1999; 34:199–201. [PMID: 10192201]
Tenner S, Baillie J, De Witt John, et al. American College of Gastroenterology Guideline: Management of Acute Pancreatitis. Am J Gastroenterol 2013; 108:1400-1415. [PMID: 23896955]
Moolsintong P, Loftus EV Jr, Chari ST, et al. Acute pancreatitis in patients with Crohn’s disease: clinical features and outcomes. Inflamm Bowel Dis 2005; 11:1080-1084. [PMID: 16306770]
Barthet M, Hastier P, Bernard JP, et al. Chronic pancreatitis and inflammatory bowel disease: true or coincidental association? Am J Gastroenterol 1999; 94:2141-2148. [PMID: 10445541]
Triantafillidis JK, Cheracakis P, Merikas EG, et al. Acute pancreatitis may precede the clinical manifestations of Crohn's disease. Am J Gastroenterol 2003; 98:1210-1211. [PMID: 12809859]
Chelimsky G, Splawski J, Czinn S, et al. Pancreatitis as a presenting symptom of inflammatory bowel disease (IBD). Am J Gastroenterol 2001; 96:287-288.
Knaflez D, Panetta F, Monti L, et al. Chronic pancreatitis as presentation of Crohn's disease in a child World J Gastroenterol 2013; 19:5204-5206. [PMID: 23964160]
Eisner TD, Goldman IS, McKinley MJ. Crohn’s disease and pancreatitis. Am J Gastroenterol. 1993; 88: 583-586. [PMID: 8470642]
Heikius B, Niemela S, Lehtola J, et al. Elevated pancreatic enzymes in inflammatory bowel disease are associated with extensive disease. Am J Gastroenterol 1999; 94:1062–1069. [PMID: 10201484]
Bokemeyer B. Asymptomatic elevation of serum lipase and amylase in conjunction with Crohn’s disease and ulcerative colitis. Z Gastroenterol 2002; 40:5–10. [PMID: 11803494]
Venkatraman D, Howarth L, Beattie RM, et al. A very high amylase can be benign in paediatric Crohn's disease BMJ Case Rep 2012; 2012:0220125917. [PMID: 22783000]
Pitchumoni CS, Rubin A, Das K. Pancreatitis in inflammatory bowel disease. J Clin Gastroenterol 2010; 44:246-253. [PMID: 20087199]
Lorusso D, Leo S, Mossa A, et al. Cholelithiasis in inflammatory bowel disease. A case-control study. Dis Colon Rectum 1990; 33:791–794. [PMID: 2202567]
Kangas E, Lehmusto P, Matikainen M. Gallstones in Crohn’s disease. Hepatogastroenterology 1990; 37:83–84.
Hutchinson R, Tyrrell PN, Kumar D, et al. Pathogenesis of gall stones in Crohn’s disease: an alternative explanation. Gut 1994; 35:94–97. [PMID: 1374640]
Lapidus A, Bangstad M, Astrom M, et al. The prevalence of gallstone disease in a defined cohort of patients with Crohn’s disease. Am J Gastroenterol 1999; 94:1261–1266. [PMID: 10235204]
Fraquelli M, Losco A, Visentin S, et al. Gallstone disease and related risk factors in patients with Crohn disease: analysis of 330 consecutive cases. Arch Intern Med 2001; 161:2201–2204. [PMID: 11575976]
Bargiggia S, Maconi G, Elli M, et al. Sonographic prevalence of liver steatosis and biliary tract stones in patients with inflammatory bowel disease: study of 511 subjects at a single center. J Clin Gastroenterol 2003; 36:417–420. [PMID: 12702985]
Parente F, Pastore L, Bargiggia S, et al. Incidence and risk factors for gallstones in patients with inflammatory bowel disease: a large case-control study. Hepatology 2007; 45:1267–1274. [PMID: 17464998]
Pereira SP, Bain IM, Kumar D, et al. Bile composition in inflammatory bowel disease: ileal disease and colectomy, but not colitis, induce lithogenic bile. Aliment Pharmcol Ther 2003; 17:923-933. [PMID: 12656695]
Lapidus A, Akerlund JE, Einarsson C. Gallbladder bile composition in patients with Crohn‘s disease. World J Gastroenterol 2006; 12:70–74. PMID: 16440420]
Damiao AO, Sipahi AM, Vezozzo DP, et al. Gallbladder hypokinesia in Crohn’s disease. Digestion 1997; 58:458-463. [PMID: 9383637]
Murray FE, McNicholas M, Stack W, et al. Impaired fatty- meal-stimulated gallbladder contractility in patients with Crohn’s disease. Clin Sci 1992; 83:689–693. [PMID: 1336439]
Annese V, Vantrappen G. Gall stones in Crohn's disease: another hypothesis. Gut 1994; 35:1676. [PMID: 1375641]
Maurer P, Haag K, Roth M, et al. No evidence for abnormal gallbladder emptying in Crohn’s disease. Hepatogastroenterology 1996; 43:807–812. [PMID: 8884294]
Trivedi CD, Pitchumoni CS. Drug-induced pancreatitis: an update. J Clin Gastroenterol 2005; 39:709–716. [PMID: 16082282]
Eland IA, Van Puijenbroek EP, Sturkenboom MJ, et al. Drug-associated acute pancreatitis: twenty-one years of spontaneous reporting in The Netherlands. Am J Gastroenterol 1999; 94:2417–2422. [PMID: 10484002]
Stein RB, Hanauer SB. Comparative tolerability of treatments for inflammatory bowel disease. Drug Saf 2000; 23:429–448. [PMID: 11085348]
Teml A, Schaeffeler E, Herrlinger KR, et al. Thiopurine treatment in inflammatory bowel disease: clinical pharmaco- logy and implication of pharmacogenetically guided dosing. Clin Pharmacokinet 2007; 46:187–208. [PMID: 17328579]
Present DH, Meltzer SJ, Krumholz MP, et al. 6-Mercapto-purine in the management of inflammatory bowel disease: short-and long-term toxicity. Ann Intern Med 1989; 111:641–649. [PMID: 2802419]
Chaparro M, Ordas I, Cabre E, et al. Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients. Inflamm Bowel Dis 2013; 19:1404-1410. [PMID: 23665964]
Weersma RK, Peters FT, Oostenbrug LE, et al. Increased incidence of azathioprine-induced pancreatitis in Crohn’s disease compared with other diseases. Aliment Pharmacol Ther 2004; 20:843–850. [PMID: 15479355]
Floyd A, Pedersen L, Nielsen GL, et al. Risk of acute pancreatitis in users of azathioprine: a population-based case-control study. Am J Gastroenterol 2003; 98:1305–1308. [PMID: 12818274]
Chun JY, Kang B, Lee YM, et al. Adverse events associated with azathioprine treatment in korean pediatric inflammatory bowel disease patients. Pediatr Gastroenterol Hepatol Nutr 2013; 16:171-177. [PMID: 24224150]
Kader HA, Wenner WJ, Telega GW, et al. Normal thiopurine methyltransferase levels do not eliminate 6-mercaptopurine or azathioprine toxicity in children with inflammatory bowel disease. J Clin Gastroenterol 2000; 30: 409-413. [PMID: 10875470]
Cappell MS, Das KM. Rapid development of pancreatitis following reuse of 6-mercaptopurine. J Clin Gastroenterol 1989; 11:679–681. [PMID: 2584670]
Weersma RK, Batstra MR, Kleibeuker JH, et al. Are pancreatic autoantibodies associated with azathioprine- induced pancreatitis in Crohn’s disease? JOP 2008; 9:283-289. [PMID: 18469440]
Garau P, Orenstein SR, Neigut DA, et al. Pancreatitis associated with olsalazine and sulfasalazine in children with ulcerative colitis. J Pediatr Gastroenterol Nutr 1994; 18:481-485. [PMID: 7520936]
Faintuch J, Mott CB, Machado MC. Pancreatitis and pancreatic necrosis during sulfasalazine therapy. Int Surg 1985; 70:271-272. [PMID: 2872181]
Rubin R. Sulfasalazine-induced fulminant hepatic failure and necrotizing pancreatitis. Am J Gastroenterol 1994; 89:789-791. [PMID: 7909645]
Debongnie JC, Dekoninck X. Sulfasalazine, 5-ASA and acute pancreatitis in Crohn’s disease. J Clin Gastroenterol 1994; 19:348-349. [PMID: 7876525]
Ransford RA, Langman MJ. Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut 2002; 51:536-539. [PMID: 12235076]
Das KM, Eastwood MA, McManus JP, et al. Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. N Engl J Med 1973; 289:491-495. [PMID: 4146729]
Fiorentini MT, Fracchia M, Galatola G, et al. Acute pancreatitis during oral 5-aminosalicylic acid therapy. Dig Dis Sci 1990; 35:1180-1182. [PMID: 10453423]
Isaacs KL, Murphy D. Pancreatitis after rectal administration of 5-aminosalicylic acid. J Clin Gastroenterol 1990; 12:198-199. [PMID: 1969872]
Keljo DJ, Sugerman KS. Pancreatitis in patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1997; 25:108–112. [PMID: 20087199]
Plotnick BH, Cohen I, Tsang T, et al. Metronidazole-induced pancreatitis. Ann Intern Med 1985; 103:891-892. [PMID: 20862338]
Sanford KA, Mayle JE, Dean HA, et al. Metronidazole associated pancreatitis. Ann Intern Med 1988; 109:756-757. [PMID: 11054984]
Celifarco A, Warschauer C, Burakoff R. Metronidazole induced pancreatitis. Am J Gastroenterol 1989; 84:958-960. [PMID: 2756988]
Corey WA, Doebbeling BN, DeJong KJ, et al. Metronidazole induced acute pancreatitis. Rev Infect Dis 1991; 13:1213-1215. [PMID: 1775854]
Sura ME, Heinrich KA, Suseno M. Metronidazole associated pancreatitis. Ann Pharmacother 2000; 34:1152-1155. [PMID: 11054984]
Feola DJ, Thornton AC. Metronidazole induced pancreatitis in a patient with recurrent vaginal trichomoniasis. Pharmacotherapy 2002; 22:1508-1510. [PMID: 12432979]
Nigwekar SU, Casey KJ. Metronidazole induced pancreatitis. A case report and review of literature. JOP 2004; 5:516-519. [PMID: 15536294]
Tsesmeli NE, Giannoulis KE, Savopoulos CG, et al. Acute pancreatitis as a possible consequence of metronidazole during a relapse of ulcerative colitis. Eur J Gastroenterol Hepatol 2007; 19:805-806. [PMID: 17700268]
Buchler M, Malfertheiner P, Friess H, et al. The penetration of antibiotics into human pancreas. Infection 1989; 17:20-25. [PMID: 2921086]
Legge DA, Hoffman HN, Carlson HC. Pancreatitis as a complication of regional enteritis of the duodenum. Gastroenterology 1971; 61:834-837. [PMID: 5125685]
Pandol SJ, Saluja AK, Imrie CW, et al. Acute pancreatitis: bench to the bedside. Gastroenterology 2007; 132:1127–1251. [PMID: 17383433]
Nugent FW, Roy MA. Duodenal Crohn’s disease: an analysis of 89 cases. Am J Gastroenterol 1989; 84:249–254. [PMID: 2919581]
Yung K, Oviedo J, Farraye FA, et al. Ampullary stenosis with biliary obstruction in duodenal Crohn’s disease: a case report and review of the literature. Dig Dis Sci 2005; 50:1118-1121. [PMID: 15986865]
Newman LH, Wellinger JR, Present DH, et al. Crohn’s disease of the duodenum associated with pancreatitis: a case report and review of the literature. Mt Sinai J Med 1987; 54:429-432. [PMID: 3309634]
Klein S, Greenstein AJ, Sachar DB. Duodenal fistulas in Crohn’s disease. J Clin Gastroenterol 1987; 9:46-49.
Das KM. Relationship of extraintestinal involvements in inflammatory bowel disease: new insights into autoimmune pathogenesis. Dig Dis Sci 1999; 44:1–13. [PMID: 9952216]
Koutroubakis IE, Drygiannakis D, Karmiris K, et al. Pancreatic autoantibodies in Greek patients with inflammatory bowel disease. Dig Dis Sci 2005; 50:2330-2334. [PMID: 16416183]
Fricke H, Birkhofer A, Folwaczny C, et al. Characterization of antigens from the human exocrine pancreatic tissue (Pag) relevant as target antigens for autoantibodies in Crohn’s disease. Eur J Clin Invest 1999; 29:41-45. [PMID: 10092987]
Torok HP, Folwaczny C. Pancreatic autoantibodies in Crohn’s disease: a feasible diagnostic tool? Eur J Gastroenterol Hepatol 2005; 17:37-39. [PMID: 15647638]
Seibold F, Weber P, Jenss H, et al. Antibodies to a trypsin sensitive pancreatic antigen in chronic inflammatory bowel disease: specific markers for a subgroup of patients with Crohn’s disease. Gut 1991; 32:1192-1197. [PMID: 1955175]
Gschwantler M, Kogelbauer G, Klose W, et al. The pancreas as a site of granulomatous inflammation in Crohn's disease. Gastroenterol 1995; 108:1246-1249. [PMID: 7698591]
Kadayakkara DK, Beatty PL, Turner MS, et al. Inflammation driven by overexpression of the hypoglycosylated abnormal mucin 1 (MUC1) links inflammatory bowel disease and pancreatitis. Pancreas 2010; 39:510-515. [PMID: 20084048]
Yoshida K, Toki F, Takeuchi T et al. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci 1995; 40:1561-1568. [PMID: 7628283]
Okazaki K, Kawa S, Kamisawa T, et al. Japanese clinical guidelines for autoimmune pancreatitis. Pancreas 2009; 38:849-866. [PMID: 19745774]
Ketwaroo GA, Sheth S. Autoimmune pancreatitis. Gastroenterol Rep 2013; 1:27-32.
Park SH, Kim D, Ye BD, et al. The characteristics of ulcerative colitis associated with autoimmune pancreatitis. J Clin Gastroenterol 2013; 47:520-525. [PMID: 23426453]
Kamisawa T, Chari ST, Giday SA, et al. Clinical profile of autoimmune pancreatitis and its histological subtypes: an international multicenter survey. Pancreas 2011; 40:809-814. [PMID: 21747310]
Navaneethan U, Liu X, Bennett AE, et al. IgG4-associated ampullitis and cholangiopathy in Crohn's disease. J Crohns Colitis 2011; 5:451-456. [PMID: 21939919]
Ishikawa T, Haruta J, Yamaguchi T, et al. A case of type 2 autoimmune pancreatitis associated with Crohn disease. Nihon Shokakibyo Gakkai Zasshi 2013; 110:875-882. [PMID: 23648545]
Ravi K, Chari ST, Vege SS, et al. Inflammatory bowel disease in the setting of autoimmune pancreatitis. Inflamm Bowel Dis 2009; 15:1326-1330. [PMID: 19235915]
Triantafillidis JK, Cheracakis P, Hereti IA, et al. Acute idiopathic pancreatitis complicating active Crohn's disease: favorable response to Infliximab treatment. Am J Gastroenterol 2000; 95:3334-3335. [PMID: 11095387]
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