|
1
|
Del Gaudio A, Covello C, Di Vincenzo F, De Lucia SS, Mezza T, Nicoletti A, Siciliano V, Candelli M, Gasbarrini A, Nista EC. Drug-Induced Acute Pancreatitis in Adults: Focus on Antimicrobial and Antiviral Drugs, a Narrative Review. Antibiotics (Basel) 2023; 12:1495. [PMID: 37887196 PMCID: PMC10604068 DOI: 10.3390/antibiotics12101495] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 09/26/2023] [Accepted: 09/26/2023] [Indexed: 10/28/2023] Open
Abstract
Acute pancreatitis (AP) is an acute inflammation of the pancreas caused by the activation of digestive enzymes in the pancreatic tissue. The main causes of AP are cholelithiasis and alcohol abuse; less commonly, it can be caused by drugs, with a prevalence of up to 5%. Causal associations between drugs and pancreatitis are largely based on case reports or case series with limited evidence. We reviewed the available data on drug-induced AP, focusing on antimicrobial drugs and antivirals, and discussed the current evidence in relation to the classification systems available in the literature. We found 51 suspected associations between antimicrobial and antiviral drugs and AP. The drugs with the most evidence of correlation are didanosine, protease inhibitors, and metronidazole. In addition, other drugs have been described in case reports demonstrating positive rechallenge. However, there are major differences between the various classifications available, where the same drug being assigned to different probability classes. It is likely that the presence in multiple case reports of an association between acute pancreatitis and a drug should serve as a basis for conducting prospective randomized controlled trials to improve the quality of the evidence.
Collapse
Affiliation(s)
- Angelo Del Gaudio
- Center for Diagnosis and Treatment of Digestive Diseases, Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (A.D.G.); (C.C.); (F.D.V.)
| | - Carlo Covello
- Center for Diagnosis and Treatment of Digestive Diseases, Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (A.D.G.); (C.C.); (F.D.V.)
| | - Federica Di Vincenzo
- Center for Diagnosis and Treatment of Digestive Diseases, Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (A.D.G.); (C.C.); (F.D.V.)
| | - Sara Sofia De Lucia
- Center for Diagnosis and Treatment of Digestive Diseases, Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (A.D.G.); (C.C.); (F.D.V.)
| | - Teresa Mezza
- Pancreas Unit, Centro Malattie Apparato Digerente, Medicina Interna e Gastroenterologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (T.M.); (A.N.)
| | - Alberto Nicoletti
- Pancreas Unit, Centro Malattie Apparato Digerente, Medicina Interna e Gastroenterologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (T.M.); (A.N.)
| | - Valentina Siciliano
- Laboratory and Infectious Diseases Sciences, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy;
| | - Marcello Candelli
- Emergency, Anesthesiological and Reanimation Sciences, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
| | - Antonio Gasbarrini
- Center for Diagnosis and Treatment of Digestive Diseases, Gastroenterology Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (A.D.G.); (C.C.); (F.D.V.)
| | - Enrico Celestino Nista
- Pancreas Unit, Centro Malattie Apparato Digerente, Medicina Interna e Gastroenterologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy; (T.M.); (A.N.)
| |
Collapse
|
|
2
|
Massironi S, Fanetti I, Viganò C, Pirola L, Fichera M, Cristoferi L, Capurso G, Invernizzi P, Danese S. Systematic review-pancreatic involvement in inflammatory bowel disease. Aliment Pharmacol Ther 2022; 55:1478-1491. [PMID: 35505465 PMCID: PMC9322673 DOI: 10.1111/apt.16949] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/28/2022] [Accepted: 04/18/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic inflammatory immune-mediated disorder of the gut with frequent extra-intestinal complications. Pancreatic involvement in IBD is not uncommon and comprises a heterogeneous group of conditions, including acute pancreatitis (AP), chronic pancreatitis (CP), autoimmune pancreatitis (AIP) and pancreatic exocrine insufficiency (PEI); however, data on such an association remain sparse and heterogeneous. METHOD PubMed/MEDLINE and EMBASE databases were searched for studies investigating pancreatic involvement in patients with IBD. RESULTS Four thousand one hundred and twenty-one records were identified and 547 screened; finally, 124 studies were included in the review. AP is the most frequent pancreatic manifestation in IBD; the majority of AP cases in IBD are due to gallstones and drugs but cases of idiopathic AP are increasingly reported. AIP is a rare disease, but a strong association with IBD has been demonstrated, especially for type 2 and ulcerative colitis. The pathogenetic link between IBD and AIP remains unclear, but an immune-mediated pathway seems plausible. An association between CP and PEI with IBD has also been suggested, but data are to date scarce and conflicting. CONCLUSION This is the first systematic review of the association between IBD and pancreatic diseases. Gallstones and drugs should be considered the most probable causes of AP in IBD, with type 2 AIP also being possible.
Collapse
Affiliation(s)
- Sara Massironi
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Ilaria Fanetti
- Gastroenterology and Endoscopy Unit, ASST Ovest MilaneseLegnano HospitalLegnanoItaly
| | - Chiara Viganò
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Lorena Pirola
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Maria Fichera
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Laura Cristoferi
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Gabriele Capurso
- Pancreas Translational & Clinical Research Center, Pancreato‐Biliary Endoscopy & Endosonography DivisionSan Raffaele Scientific Institute IRCCSMilanItaly
| | - Pietro Invernizzi
- Department of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Silvio Danese
- Gastroenterology and EndoscopyIRCCS Ospedale San Raffaele and Vita‐Salute San Raffaele UniversityMilanItaly
| |
Collapse
|
|
3
|
Weissman S, Aziz M, Perumpail RB, Mehta TI, Patel R, Tabibian JH. Ever-increasing diversity of drug-induced pancreatitis. World J Gastroenterol 2020; 26:2902-2915. [PMID: 32587438 PMCID: PMC7304112 DOI: 10.3748/wjg.v26.i22.2902] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 03/27/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
With over 100000 hospital admissions per annum, acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has far-reaching impact well beyond. It has become increasingly recognized that drug-induced pancreatitis (DIP), despite accounting for less than 3% of all cases, represents an important and growing though often inconspicuous cause of acute pancreatitis. Nevertheless, knowledge of DIP is often curtailed by the limited availability of evidence needed to implicate given agents, especially for non-prescription medications. Indeed, the majority of available data is derived from case reports, case series, or case control studies. Furthermore, the mechanism of injury and causality for many of these drugs remain elusive as a definitive correlation is generally not established (< 10% of cases). Several classification systems have been proposed, but no single system has been widely adopted, and periodic updates are required in light of ongoing pharmacologic expansion. Moreover, infrequently prescribed medications or those available over-the-counter (including herbal and other alternative remedies) are often overlooked as a potential culprit of acute pancreatitis. Herein, we review the ever-increasing diversity of DIP and the potential mechanisms of injury with the goal of raising awareness regarding the nature and magnitude of this entity. We believe this manuscript will aid in increasing both primary and secondary prevention of DIP, thus ultimately facilitating more expedient diagnosis and a decrease in DIP-related morbidity.
Collapse
Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack University-Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Muhammad Aziz
- Department of Medicine, University of Toledo Medical Center, Toledo, OH 43614, United States
| | - Ryan B Perumpail
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
| | - Tej I Mehta
- Department of Interventional Radiology, Johns Hopkins University Hospital, Baltimore, MD 21205, United States
| | - Rutwik Patel
- Department of Medicine, Hackensack University-Palisades Medical Center, North Bergen, NJ 07047, United States
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342 and David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
| |
Collapse
|
|
4
|
Wolfe D, Kanji S, Yazdi F, Barbeau P, Rice D, Beck A, Butler C, Esmaeilisaraji L, Skidmore B, Moher D, Hutton B. Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations. PLoS One 2020; 15:e0231883. [PMID: 32302358 PMCID: PMC7164626 DOI: 10.1371/journal.pone.0231883] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 04/02/2020] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations. METHODS A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency. RESULTS Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis. DISCUSSION Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations. REGISTRATION CRD42017060473.
Collapse
Affiliation(s)
- Dianna Wolfe
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Salmaan Kanji
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Department of Pharmacy, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Fatemeh Yazdi
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Pauline Barbeau
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Danielle Rice
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Andrew Beck
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Claire Butler
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Leila Esmaeilisaraji
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Becky Skidmore
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - David Moher
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Brian Hutton
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
| |
Collapse
|
|
5
|
Youssef I, Saeed N, El Abdallah M, Huevelhorst K, Zakharia K. Metronidazole-Induced Pancreatitis: Is There Underrecognition? A Case Report and Systematic Review of the Literature. Case Rep Gastrointest Med 2019; 2019:4840539. [PMID: 31281684 PMCID: PMC6590551 DOI: 10.1155/2019/4840539] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 05/06/2019] [Indexed: 01/15/2023] Open
Abstract
INTRODUCTION Acute pancreatitis (AP) is the most common cause of gastroenterological hospitalization in the USA, with a mortality ranging from 5 to 20%. Up to 80% of cases are caused by cholelithiasis and alcohol abuse. Less common etiologies that need to be explored include hypertriglyceridemia, trauma, ERCP, infections, and drugs. A number of medications are known to cause acute pancreatitis, with 0.3-1.4% of all cases of pancreatitis being drug induced (DIP). Here, we present a case of metronidazole-induced acute pancreatitis. CASE SUMMARY A 60-year-old female presented with constant severe epigastric pain associated with nausea, vomiting, and anorexia for one day. She had no past medical history of alcohol use or hypertriglyceridemia and was s/p cholecystectomy in the distant past. Symptoms had begun three days after starting metronidazole for Clostridium difficile colitis. Lipase was > 396, and CT abdomen revealed peripancreatic fat stranding. She was diagnosed with AP, metronidazole was suspected to be responsible and hence stopped, and supportive management initiated. Her symptoms improved rapidly, and pancreatic enzymes normalized within 2 days. Of note, she had had an episode of acute pancreatitis 3 years ago, also following metronidazole use, with resolution at discontinuation of the drug. She had concurrently been on omeprazole during both episodes. DISCUSSION Metronidazole is a commonly used antibiotic and is infrequently reported as a cause of DIP. Our review suggests the possibility of a dose-response and duration-response effect between metronidazole use and occurrence of pancreatitis. The most common presenting symptom and sign was moderate to severe epigastric pain and tenderness, accompanied by nausea/vomiting. Symptoms usually start within 2-7 days of starting the medication and usually resolve 2-5 days after discontinuation of therapy and pancreatitis treatment. The most common causative dose was 1-1.5 g/day. Our review also supports findings by Norgaard et al. suggesting that concurrent use of omeprazole potentiates the risk of metronidazole-induced pancreatitis. CONCLUSION Metronidazole is a commonly used antibiotic that may cause metronidazole-induced pancreatitis, especially if patients are concurrently taking PPIs. Awareness needs to be raised amongst clinicians regarding this association, in order to correctly identify etiology of pancreatitis and discontinue metronidazole promptly when suspected as the causative factor.
Collapse
Affiliation(s)
- Ibrahim Youssef
- Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Naba Saeed
- Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, Beaumont Health, Dearborn, Michigan, USA
| | | | - Kara Huevelhorst
- Department of Radiology, Beaumont Health–Dearborn, Dearborn, Michigan, USA
| | - Kais Zakharia
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
| |
Collapse
|
|
6
|
Fousekis FS, Theopistos VI, Katsanos KH, Christodoulou DK. Pancreatic Involvement in Inflammatory Bowel Disease: A Review. J Clin Med Res 2018; 10:743-751. [PMID: 30214645 PMCID: PMC6135003 DOI: 10.14740/jocmr3561w] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 08/21/2018] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a multisystemic disease, and pancreatic manifestations of IBD are not uncommon. The incidence of several pancreatic diseases in Crohn’s disease and ulcerative colitis is more frequent compared to the general population. Pancreatic manifestations in IBD include a wide heterogenic group of disorders and abnormalities of the pancreas and range from mild self-limited diseases to severe disorders. Acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, pancreatic autoantibodies, exocrine pancreatic insufficiency and asymptomatic imaging and laboratory abnormalities are included in related-IBD pancreatic manifestations. Involvement of the pancreas in IBD may be the result of IBD itself or of medications used.
Collapse
Affiliation(s)
- Fotios S Fousekis
- Department of Gastroenterology and Hepatology, Medical School of Ioannina, Greece
| | | | | | | |
Collapse
|
|
7
|
Hung WY, Abreu Lanfranco O. Contemporary review of drug-induced pancreatitis: A different perspective. World J Gastrointest Pathophysiol 2014; 5:405-415. [PMID: 25400984 PMCID: PMC4231505 DOI: 10.4291/wjgp.v5.i4.405] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Revised: 06/17/2014] [Accepted: 07/29/2014] [Indexed: 02/06/2023] Open
Abstract
Although gallstone and alcohol use have been considered the most common causes of acute pancreatitis, hundreds of frequently prescribed medications are associated with this disease state. The true incidence is unknown since there are few population based studies available. The knowledge of drug induced acute pancreatitis is limited by the availability and the quality of the evidence as the majority of data is extrapolated from case reports. Establishing a definitive causal relationship between a drug and acute pancreatitis poses a challenge to clinicians. Several causative agent classification systems are often used to identify the suspected agents. They require regular updates since new drug induced acute pancreatitis cases are reported continuously. In addition, infrequently prescribed medications and herbal medications are often omitted. Furthermore, identification of drug induced acute pancreatitis with new medications often requires accumulation of post market case reports. The unrealistic expectation for a comprehensive list of medications and the multifactorial nature of acute pancreatitis call for a different approach. In this article, we review the potential mechanisms of drug induced acute pancreatitis and provide the perspective of deductive reasoning in order to allow clinicians to identify potential drug induced acute pancreatitis with limited data.
Collapse
|
|
8
|
Metronidazole-induced pancreatitis. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2010; 2010:523468. [PMID: 20862338 PMCID: PMC2939404 DOI: 10.1155/2010/523468] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/20/2009] [Revised: 06/20/2010] [Accepted: 08/13/2010] [Indexed: 11/27/2022]
Abstract
Case Summary. A 25-year-old caucasian lady presented to the Accident & Emergency department complaining of acute onset severe epigastric pain radiating through to the back with associated nausea and vomiting. A diagnosis of acute pancreatitis was made. Symptoms commenced after the third dose of Metronidazole therapy prescribed for a recurrent periodontal abscess. The patient described a similar episode 10 months previously. On neither occasion were any other medications being taken, there was no history of alcohol abuse and no other gastro-intestinal aetiology could be identified on imaging. Symptoms resolved quickly upon discontinuation of the antibiotic agent. We conclude therefore that Metronidazole can reasonably be identified as the only potential causative agent.
Discussion. The proportion of cases of pancreatitis caused by drugs is estimated to be around 2% in the general population. The exact mechanism of action of Metronidazole induced pancreatitis is unclear but a trigger role for the drug seems likely.
Conclusion. This case provides the eighth report of Metronidazole induced pancreatitis. All of the cases were reported in females and ran a benign course.Early diagnosis, discontinuation of the drug and supportive care will lead to a successful recovery in the majority of cases.
Collapse
|
|
9
|
Abstract
Crohn's disease and ulcerative colitis, together popularly known as inflammatory bowel disease (IBD), are characterized by a number of extraintestinal manifestations. Although infrequent, acute pancreatitis, and less often chronic pancreatitis, may occur as a result of the disease itself or secondary to the medications used in the treatment. The increased incidence of acute pancreatitis in Crohn's disease can be explained based on the high predisposition to cholesterol as well as pigment stones as a result of ileal disease, anatomic abnormalities of the duodenum, immunologic disturbances associated with IBD, and, above all, to the side effects of many medications used in the treatment. Sulfasalazine, 5-aminosalicylic acid, azathioprine, and 6-mercaptopurine are well known to cause acute pancreatitis as a result of a possible idiosyncratic mechanism. Crohn's disease and ulcerative colitis share many clinical manifestations and treatment modalities. Nonspecific elevations of serum pancreatic enzymes in IBD make it difficult to avoid over diagnosis of acute pancreatitis, particularly in patients with Crohn's disease who suffer from abdominal pain often. The IBD-pancreas association is further reflected in many reports of exocrine as well as endocrine pancreatic insufficiency.
Collapse
|
|
10
|
Xin MJ, Chen H, Luo B, Sun JB. Severe acute pancreatitis in the elderly: Etiology and clinical characteristics. World J Gastroenterol 2008; 14:2517-21. [PMID: 18442198 PMCID: PMC2708362 DOI: 10.3748/wjg.14.2517] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the etiology and clinical characteristics of severe acute pancreatitis (SAP) in elderly patients (≥ 60 years of age).
METHODS: We reviewed retrospectively all the SAP cases treated in Xuanwu Hospital in Beijing between 2000 and 2007.
RESULTS: In 169 patients with SAP, 94 were elderly and 16 died. Biliary and idiopathic etiologies were the first two causes that accounted for over 90% of SAP in the elderly. Biliary, hyperlipemic and alcoholic etiologies were the first three causes in the young. The proportion of co-morbidity of cholelithiasis, biliary infection, hypertension and coronary heart disease in the aged was significantly higher than that in their young partners. The scores of APACHE II and Ranson were also significantly higher in the elderly except the CT score. Organ failures were more common in the elderly, but the local pancreatic complications were not different between the two groups. Mortality of the aged was correlated with the severity of SAP, multiple co-morbidity and incidence of multiple organ dysfunction syndrome (MODS). MODS was the main cause of death.
CONCLUSION: The etiology of SAP in the elderly is quite different from that in the young. Biliary and unknown factors are main causes in the aged. The elderly are subject to major organ failures but there is no difference in the occurrence of local pancreatic complications between the elderly and the young. It is crucial to monitor and improve the functions of major organs so as to prevent MODS in the aged with SAP.
Collapse
|
|
11
|
Javier Romero Ganuza F. Pancreatitis asociada a metronidazol. GASTROENTEROLOGIA Y HEPATOLOGIA 2008; 31:264-5. [DOI: 10.1157/13117906] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
|
|
12
|
Affiliation(s)
- Anil R Balani
- Division of Gastroenterology, Hepatology and Nutrition, Winthrop University Hospital, Mineola, New York 11501, USA
| | | |
Collapse
|
|
13
|
Badalov N, Baradarian R, Iswara K, Li J, Steinberg W, Tenner S. Drug-induced acute pancreatitis: an evidence-based review. Clin Gastroenterol Hepatol 2007; 5:648-61; quiz 644. [PMID: 17395548 DOI: 10.1016/j.cgh.2006.11.023] [Citation(s) in RCA: 362] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The diagnosis of drug-induced acute pancreatitis often is difficult to establish. Although some medications have been shown to cause acute pancreatitis with a large body of evidence, including rechallenge, some medications have been attributed as a cause of acute pancreatitis merely by a single published case report in which the investigators found no other cause. In addition, some medications reported to have caused acute pancreatitis have obvious patterns of presentation, including the time from initiation to the development of disease (latency). There also appear to be patterns in the severity of disease. After reviewing the literature, we have classified drugs that have been reported to cause acute pancreatitis based on the published weight of evidence for each agent and the pattern of clinical presentation. Based on our analysis of the level of evidence, 4 classes of drugs could be identified. Class I drugs include medications in which at least 1 case report described a recurrence of acute pancreatitis with a rechallenge with the drug. Class II drugs include drugs in which there is a consistent latency in 75% or more of the reported cases. Class III drugs include drugs that had 2 or more case reports published, but neither a rechallenge nor a consistent latency period. Class IV drugs were similar to class III drugs, but only 1 case report had been published. Our analysis allows an evidence-based approach when suspecting a drug as causing acute pancreatitis.
Collapse
Affiliation(s)
- Nison Badalov
- Division of Gastroenterology, Maimonides Medical Center, Mount Sinai School of Medicine, Brooklyn, New York 11235, USA
| | | | | | | | | | | |
Collapse
|
|
14
|
Abstract
Amiodarone, a class III antiarrhythmic drug, is one of the most effective drugs used in the treatment of ventricular and paroxysmal supraventricular tachyarrhythmia. Adverse effects of amiodarone including pulmonary toxicity, hepatotoxicity, aggravation of arrhythmia, and thyroid diseases are well understood. A 66-year old woman with acute pancreatitis was admitted to our hospital with the complaint of epigastralgia radiating to both flanks for two months. Her symptoms and elevation of pancreatic enzymes did not respond to conventional medical treatment of pancreatitis for 18 d. No known causal factors for pancreatitis such as biliary tract stone, hypertriglyceridemia and alcohol consumption could be identified. Under the suspicion of amiodarone-induced acute pancreatitis, amiodarone was substituted by propafenone. Her symptoms soon alleviated and serum lipase level declined. Three months after hospital discharge, the abdominal pain did not recur. Amiodarone was approved to treat recurrent ventricular fibrillation or sustained ventricular tachyarrhythmia that has been resistant to other medications since 1986. Pancreatitis is a very rare adverse effect associated with the use of amiodarone, and only four cases of amiodarone-induced pancreatitis have been reported in literature. We report a patient who developed acute pancreatitis during amiodarone therapy.
Collapse
Affiliation(s)
- Yen-Yuan Chen
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan, China
| | | | | |
Collapse
|
|
15
|
Abstract
Dermatologists use a variety of systemic drugs, some of which can cause severe adverse reactions and even fatalities. Ivermectin, a well-tolerated drug, can cause severe neurological side effects, whereas metronidazole, in high cumulative doses, has been associated with convulsions and rarely with hepatotoxicity. Dapsone is associated with frequent hematologic side effects, such as methemoglobinemia, hemolysis, and anemia. Although hepatotoxicity is rare and usually mild and reversible with the new antifungal agents, severe cutaneous reactions (such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and anaphylaxis) have been reported. Even a relatively safe drug such as acyclovir has been reported to be the cause of renal failure and neurotoxicity. Retinoids can cause not so benign "benign" intracranial hypertension. Methotrexate can cause not only liver toxicity, but also myelosuppression and pancytopenia, which may be acute and life threatening. Nephrotoxicity is a well-recognized side effect of cyclosporine, whereas thrombotic thrombocytopenic purpura, which is associated with high morbidity and mortality, is less well known. Dermatologists should be familiar with these and other severe adverse reactions of the most popular and most used systemic medications of our trade.
Collapse
Affiliation(s)
- Edith Orion
- The Dermatology Unit, Kaplan Medical Center, Rechovot 76100, Israel.
| | | | | |
Collapse
|
|
16
|
Nørgaard M, Ratanajamit C, Jacobsen J, Skriver MV, Pedersen L, Sørensen HT. Metronidazole and risk of acute pancreatitis: a population-based case-control study. Aliment Pharmacol Ther 2005; 21:415-20. [PMID: 15709992 DOI: 10.1111/j.1365-2036.2005.02344.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Use of metronidazole has been suggested to be associated with an increased risk of acute pancreatitis in case reports. AIM To examine this issue within a proper epidemiological design. METHODS We identified 3083 incident cases of acute pancreatitis from Hospital Discharge Registries in three Danish counties and 30 830 matched population controls. From prescription databases, we extracted information on use of metronidazole with or without concomitant use of proton-pump inhibitors and/or amoxicillin, macrolides or tetracycline. RESULTS Adjusted odds ratios for acute pancreatitis in study subjects who redeemed a prescription for metronidazole within 30, 31-180, or 181-365 days before hospitalization or index date among controls were 3.0 [95% confidence interval (CI): 1.4-6.6], 1.8 (95% CI: 1.2-2.9) and 1.1 (95% CI: 0.6-1.8), respectively. Among subjects with a concomitant prescription for proton-pump inhibitors and/or amoxicillin, macrolides or tetracycline within 30, 31-180, or 181-365 days before hospitalization, or index date among controls, adjusted odds ratios were 8.3 (95% CI: 2.6-26.4), 2.7 (95% CI: 1.4-5.5), and 1.7 (95% CI: 0.6-4.8), respectively. CONCLUSION Metronidazole may increase the risk of acute pancreatitis. However, the risk seems mainly to increase when metronidazole is used in combination with other drugs used for Helicobacter pylori eradication.
Collapse
Affiliation(s)
- M Nørgaard
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus C, Denmark.
| | | | | | | | | | | |
Collapse
|
|
17
|
Daher EDF, Brunetta DM, de Silva Júnior GB, Puster RA, Patrocínio RMDSV. Pancreatic involvement in fatal human leptospirosis: clinical and histopathological features. Rev Inst Med Trop Sao Paulo 2004; 45:307-13. [PMID: 14762628 DOI: 10.1590/s0036-46652003000600002] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Hyperamylasemia has been reported in more than 65% of patients with severe leptospirosis, and the true diagnosis of acute pancreatitis is complicated by the fact that renal failure can increase serum amylase levels. Based on these data we retrospectively analyzed the clinical and histopathological features of pancreas involvement in 13 cases of fatal human leptospirosis. The most common signs and symptoms presented at admission were fever, chills, vomiting, myalgia, dehydratation, abdominal pain and diarrhea. Trombocytopenia was evident in 11 patients. Mild increased of AST and ALT levels was seen in 9 patients. Hyperamylasemia was recorded in every patient in whom it was measured, with values above 180 IU/L (3 cases). All patients presented acute renal failure and five have been submitted to dialytic treatment. The main cause of death was acute respiratory failure due to pulmonary hemorrhage. Pancreas fragments were collected for histological study and fat necrosis was the criterion used to classify acute pancreatitis. Histological pancreatic findings were edema, mild inflammatory infiltrate of lymphocytes, hemorrhage, congestion, fat necrosis and calcification. All the patients infected with severe form of leptospirosis who develop abdominal pain should raise the suspect of pancreatic involvement.
Collapse
Affiliation(s)
- Elizabeth De Francesco Daher
- Hospital Universit rio Walter Cant dio, Departamento de Medicina Cl nica, Faculdade de Medicina, Universidade Federal do Cear , Fortaleza, CE, Brasil.
| | | | | | | | | |
Collapse
|
|
18
|
Feola DJ, Thornton AC. Metronidazole-induced pancreatitis in a patient with recurrent vaginal trichomoniasis. Pharmacotherapy 2002; 22:1508-10. [PMID: 12432979 DOI: 10.1592/phco.22.16.1508.33691] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Recurrent acute pancreatitis associated with metronidazole developed in a 49-year-old woman who was taking the drug as treatment for vaginal trichomoniasis. The lack of alternative effective therapies for trichomoniasis governed the decision to rechallenge the patient with metronidazole despite a vague history of this reaction on a previous occasion. Six reports of this reaction are found in the literature. The patient was admitted to the hospital 12 hours after taking a single dose of metronidazole. Severe epigastric pain and elevated amylase and lipase concentrations led to the diagnosis of acute pancreatitis, although results of an abdominal ultrasound were unremarkable. The patient made a full recovery. Although this reaction occurs infrequently, this case report illustrates the need to develop additional therapies for treatment of trichomoniasis.
Collapse
Affiliation(s)
- David J Feola
- Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, USA
| | | |
Collapse
|
|
19
|
Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2001; 10:173-88. [PMID: 11499857 DOI: 10.1002/pds.547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
|