Acute pancreatitis causes: Difference between revisions

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==Overview==
==Overview==
Acute pancreatitis may be either idiopathic or caused by [[alcohol]], [[gallstones]], [[trauma]], [[steroids]], [[mumps]], [[autoimmune diseases]], [[ERCP]], [[hypercalcemia]], [[hyperlipidemia]], [[hypertriglyceridemia]] or certain medications.
Acute pancreatitis may be either idiopathic or caused by [[alcohol]], [[gallstones]], [[trauma]], [[steroids]], [[mumps]], [[autoimmune diseases]], [[ERCP]], [[hypercalcemia]], [[hyperlipidemia]], [[hypertriglyceridemia]] or certain medications. Gallstones are the most common cause of acute pancreatitis, followed by chronic alcohol consumption (4-5 drinks daily for ~5 years).<ref name="pmid17079934">{{cite journal| author=Yadav D, Lowenfels AB| title=Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review. | journal=Pancreas | year= 2006 | volume= 33 | issue= 4 | pages= 323-30 | pmid=17079934 | doi=10.1097/01.mpa.0000236733.31617.52 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17079934  }}</ref>  There are numerous primary and secondary causes of acute pancreatitis that must be considered in a patient's work up.


==Causes==
==Causes==
Gallstones are the most common cause of acute pancreatitis, followed by chronic alcohol consumption (4-5 drinks daily for ~5 years).<ref name="pmid170799342">{{cite journal| author=Yadav D, Lowenfels AB| title=Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review. | journal=Pancreas | year= 2006 | volume= 33 | issue= 4 | pages= 323-30 | pmid=17079934 | doi=10.1097/01.mpa.0000236733.31617.52 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17079934  }}</ref> However; there are numerous primary and secondary causes of acute pancreatitis that must be considered in a patient's work up.
=== Synopsis ===
The following table summarizes the most common causes of acute pancreatitis:
{| class="wikitable"
!Cause
!Frequency
!Comment
|-
|Gallstones
|40%
|Gallstones or sludge
|-
|Alcohol
|30%
|4-5 drinks daily for 5 years
|-
|Hypertriglyceridemia
|2-5%
|>1000 mg/dL
|-
|Genetic
|unknown
|Causing recurrent acute or chronic pancreatitis
|-
|Drug-induced
|<5%
|Most commonly Azathioprine, 6-mercaptopurine, Didanosine, Valproid acid, ACEi, mesalamine
|-
|Autoimmune
|<1%
|Presents as Type I or Type II
|-
|ERCP (Iatrogenic)
|5-10% of procedures
|Treated with rectal NSAIDs or temporary pancreatic duct stent placement
|-
|Trauma
|Blunt force trauma to the mid-abodmen
|Blunt force trauma to the mid-abdomen
|-
|Infection
|<1%
|Primarily caused by CMV, Mumps, or EBV. May be caused by Ascaris or Clonorchis
|-
|Surgical
|5-10% of patients on cardiopulmonary bypass
| -
|-
|Obstruction
|Rare
|Caused by Celiac disease, Crohn's disease, and perpetrated by pancreas divisium or sphincter of oddi dysfunction
|}
==== Anatomical causes ====
Sphincter of Oddi dysfunction and pancreas divisium have been traditionally associated with the development of acute pancreatitis; however, recent data suggests otherwise.<ref name="pmid229821832">{{cite journal| author=Coté GA, Imperiale TF, Schmidt SE, Fogel E, Lehman G, McHenry L et al.| title=Similar efficacies of biliary, with or without pancreatic, sphincterotomy in treatment of idiopathic recurrent acute pancreatitis. | journal=Gastroenterology | year= 2012 | volume= 143 | issue= 6 | pages= 1502-1509.e1 | pmid=22982183 | doi=10.1053/j.gastro.2012.09.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22982183  }}</ref> Pancreas divisium has been associated with genetic mutations that may be the true underlying cause of pancreatitis. Alternatively, the presence of the abnormal anatomy alone may not predispose patients to acute pancreatitis; however, in lieu of a genetic mutation may superimpose on the existing anatomical variation to contribute in the pathogenesis of acute pancreatitis.<ref name="pmid22306946">{{cite journal| author=DiMagno MJ, Dimagno EP| title=Pancreas divisum does not cause pancreatitis, but associates with CFTR mutations. | journal=Am J Gastroenterol | year= 2012 | volume= 107 | issue= 2 | pages= 318-20 | pmid=22306946 | doi=10.1038/ajg.2011.430 | pmc=3458421 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22306946  }}</ref>
==== Environmental causes ====
Chronic alcoholism and smoking have been associated with the development of acute pancreatitis. Though alcohol has been proposed to be pathogenic in combination with the presence of an underlying genetic mutation. Alcoholism causing pancreatitis is more common in males than females. This may be due to the propensity of males to consume alcohol more than females, or due to the genetic mutations occurring more commonly in males.<ref name="pmid21029787">{{cite journal| author=Coté GA, Yadav D, Slivka A, Hawes RH, Anderson MA, Burton FR et al.| title=Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis. | journal=Clin Gastroenterol Hepatol | year= 2011 | volume= 9 | issue= 3 | pages= 266-73; quiz e27 | pmid=21029787 | doi=10.1016/j.cgh.2010.10.015 | pmc=3043170 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21029787  }}</ref>
==== Iatrogenic causes ====
Common iatrogenic causes of pancreatitis include ERCP procedures as well as use of medication. Hundreds of medications have been implicated in causing pancreatitis; however, the most common drugs include:
* Steroid use
* Azathioprine
* 6-Mercaptopurine
* Didanosine
* Valproic acid
* Angiotensin Converting Enzyme inhibitors (ACEi)
* Mesalamine
It is extremely difficult to identify a particular drug which may be responsible for the development of pancreatitis as there are usually multiple possibilities to the underlying etiology of the pancreatitis in patients with comorbidities; however, patients hospitalized for acute pancreatitis are often found to be using one or more drugs associated with the development of the disease.<ref name="pmid26335010">{{cite journal| author=Bertilsson S, Kalaitzakis E| title=Acute Pancreatitis and Use of Pancreatitis-Associated Drugs: A 10-Year Population-Based Cohort Study. | journal=Pancreas | year= 2015 | volume= 44 | issue= 7 | pages= 1096-104 | pmid=26335010 | doi=10.1097/MPA.0000000000000406 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26335010  }}</ref>
==== Genetic causes ====
Several gene mutations have been implicated as a cause of acute pancreatitis, the most common of which include:<ref name="pmid23622139">{{cite journal| author=Whitcomb DC| title=Genetic risk factors for pancreatic disorders. | journal=Gastroenterology | year= 2013 | volume= 144 | issue= 6 | pages= 1292-302 | pmid=23622139 | doi=10.1053/j.gastro.2013.01.069 | pmc=3684061 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23622139  }}</ref>
* CFTR mutation
* PRSS-1
* SPINK-1
* Chymotrypsin C
* Claudin-2
* Calcium sensing receptors
===Common Causes===
===Common Causes===
A common [[mnemonic]] for the causes of pancreatitis spells "I get smashed", an allusion to heavy drinking (one of the many causes):  
A common [[mnemonic]] for the causes of pancreatitis spells "I get smashed", an allusion to heavy drinking (one of the many causes):  
*I - [[idiopathic]]
*I - [[idiopathic]]
*G - [[gallstone]]. Gallstones that travel down the common [[bile duct]] and which subsequently get stuck in the [[Ampulla of Vater]] can cause obstruction in the outflow of pancreatic juices from the pancreas into the [[duodenum]]. The backflow of these digestive juices causes lysis (dissolving) of pancreatic cells and subsequent pancreatitis.
*G - [[gallstone]]. Gallstones that travel down the common [[bile duct]] and which subsequently get stuck in the [[Ampulla of Vater]] can cause obstruction in the outflow of pancreatic juices from the pancreas into the [[duodenum]]. The backflow of these digestive juices causes lysis (dissolving) of pancreatic cells and subsequent pancreatitis.
*E - [[ethanol]] ([[alcoholic beverage|alcohol]])
*E - [[ethanol]] ([[alcoholic beverage|alcohol]]) - Alcohol has been proposed to cause acute pancreatitis in combination with genetic factors. It is more commonly a cause in males than females. This may be due to the propensity of males to chronically abuse alcohol, or by genetic factors more commonly present in males.
*T - [[physical trauma|trauma]]
*T - [[physical trauma|trauma]]
*S - [[steroids]]
*S - [[steroids]] - Commonly used in patients with autoimmune diseases. Type I presents with obstructive jaundice and elevated IgG4 levels. Type II presents in younger patients with no increase in IgG4 levels.
*M - [[mumps]] ([[paramyxovirus]]) and other viruses ([[Epstein-Barr virus]], [[Cytomegalovirus]])
*M - [[mumps]] ([[paramyxovirus]]) and other viruses ([[Epstein-Barr virus]], [[Cytomegalovirus]])
*A - [[autoimmune disease]] ([[Polyarteritis nodosa]], [[Systemic lupus erythematosus]])
*A - [[autoimmune disease]] ([[Polyarteritis nodosa]], [[Systemic lupus erythematosus]])
Line 18: Line 98:
*H - [[hypercalcemia]], [[hyperlipidemia]]/[[hypertriglyceridemia]] and [[hypothermia]]
*H - [[hypercalcemia]], [[hyperlipidemia]]/[[hypertriglyceridemia]] and [[hypothermia]]
*E - [[ERCP]] (''E''ndoscopic ''R''etrograde ''C''holangio-''P''ancreatography - a procedure that combines [[endoscopy]] and [[fluoroscopy]])
*E - [[ERCP]] (''E''ndoscopic ''R''etrograde ''C''holangio-''P''ancreatography - a procedure that combines [[endoscopy]] and [[fluoroscopy]])
*D - [[Medication|drugs]] (''SAND'' - [[steroids]] & [[sulfonamides]], [[azathioprine]], [[NSAIDS]], [[diuretics]] such as [[furosemide]] and [[thiazides]], & [[didanosine]]) and [[duodenal ulcer]]s
*D - [[Medication|drugs]] (''SAND'' - [[steroids]] & [[sulfonamides]], [[azathioprine]], [[NSAIDS]], [[diuretics]] such as [[furosemide]] and [[thiazides]], & [[didanosine]]) and [[duodenal ulcer]]s. Drugs often present with mild pancreatitis and rarely are associated with signs of drug allergy such as rash.


===Causes by Organ System===
===Causes by Organ System===

Revision as of 17:10, 25 November 2016

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]

Overview

Acute pancreatitis may be either idiopathic or caused by alcohol, gallstones, trauma, steroids, mumps, autoimmune diseases, ERCP, hypercalcemia, hyperlipidemia, hypertriglyceridemia or certain medications. Gallstones are the most common cause of acute pancreatitis, followed by chronic alcohol consumption (4-5 drinks daily for ~5 years).[1] There are numerous primary and secondary causes of acute pancreatitis that must be considered in a patient's work up.

Causes

Gallstones are the most common cause of acute pancreatitis, followed by chronic alcohol consumption (4-5 drinks daily for ~5 years).[2] However; there are numerous primary and secondary causes of acute pancreatitis that must be considered in a patient's work up.

Synopsis

The following table summarizes the most common causes of acute pancreatitis:

Cause Frequency Comment
Gallstones 40% Gallstones or sludge
Alcohol 30% 4-5 drinks daily for 5 years
Hypertriglyceridemia 2-5% >1000 mg/dL
Genetic unknown Causing recurrent acute or chronic pancreatitis
Drug-induced <5% Most commonly Azathioprine, 6-mercaptopurine, Didanosine, Valproid acid, ACEi, mesalamine
Autoimmune <1% Presents as Type I or Type II
ERCP (Iatrogenic) 5-10% of procedures Treated with rectal NSAIDs or temporary pancreatic duct stent placement
Trauma Blunt force trauma to the mid-abodmen Blunt force trauma to the mid-abdomen
Infection <1% Primarily caused by CMV, Mumps, or EBV. May be caused by Ascaris or Clonorchis
Surgical 5-10% of patients on cardiopulmonary bypass -
Obstruction Rare Caused by Celiac disease, Crohn's disease, and perpetrated by pancreas divisium or sphincter of oddi dysfunction

Anatomical causes

Sphincter of Oddi dysfunction and pancreas divisium have been traditionally associated with the development of acute pancreatitis; however, recent data suggests otherwise.[3] Pancreas divisium has been associated with genetic mutations that may be the true underlying cause of pancreatitis. Alternatively, the presence of the abnormal anatomy alone may not predispose patients to acute pancreatitis; however, in lieu of a genetic mutation may superimpose on the existing anatomical variation to contribute in the pathogenesis of acute pancreatitis.[4]

Environmental causes

Chronic alcoholism and smoking have been associated with the development of acute pancreatitis. Though alcohol has been proposed to be pathogenic in combination with the presence of an underlying genetic mutation. Alcoholism causing pancreatitis is more common in males than females. This may be due to the propensity of males to consume alcohol more than females, or due to the genetic mutations occurring more commonly in males.[5]

Iatrogenic causes

Common iatrogenic causes of pancreatitis include ERCP procedures as well as use of medication. Hundreds of medications have been implicated in causing pancreatitis; however, the most common drugs include:

  • Steroid use
  • Azathioprine
  • 6-Mercaptopurine
  • Didanosine
  • Valproic acid
  • Angiotensin Converting Enzyme inhibitors (ACEi)
  • Mesalamine

It is extremely difficult to identify a particular drug which may be responsible for the development of pancreatitis as there are usually multiple possibilities to the underlying etiology of the pancreatitis in patients with comorbidities; however, patients hospitalized for acute pancreatitis are often found to be using one or more drugs associated with the development of the disease.[6]

Genetic causes

Several gene mutations have been implicated as a cause of acute pancreatitis, the most common of which include:[7]

  • CFTR mutation
  • PRSS-1
  • SPINK-1
  • Chymotrypsin C
  • Claudin-2
  • Calcium sensing receptors

Common Causes

A common mnemonic for the causes of pancreatitis spells "I get smashed", an allusion to heavy drinking (one of the many causes):

Causes by Organ System

Cardiovascular Cholesterol embolism, Polyarteritis nodosa
Chemical / poisoning Scorpion sting, Snake bite, Zinc, Ethanol
Dermatologic No underlying causes
Drug Side Effect Asparaginase, Azathioprine, Bexarotene, Bumetanide, Didanosine, Diuretics, Enfuvirtide, Ethanol, Exenatide, Frusemide, Isotretinoin, Linagliptin, Liraglutide, Mesalazine, Metronidazole, NSAIDS, Olsalazine, Oxyphenbutazone, Pentamidine, Sitagliptin, Steroids, Sulfonamides, Thiazide, Valproic acid
Ear Nose Throat No underlying causes
Endocrine Primary hyperparathyroidism
Environmental No underlying causes
Gastroenterologic Bile duct cysts,Cholangiocarcinoma, Choledochal cyst, Choledocholithiasis, Cholelithiasis, Duodenal ulcer, Gallstones , Gastric ulcer, Long common duct, Pancreas divisum, Pancreas duct obstruction, Pancreatic abnormalities, Pancreatic cancer, Pancreatic cysts , Peptic ulcer , Reye syndrome, Hereditary pancreatitis, Cystic fibrosis
Genetic Apolipoprotein C-II deficiency, Cystic fibrosis, Familial hypertriglyceridaemia, Familial partial lipodystrophy type 1 , Hereditary pancreatitis, Lipoprotein lipase deficiency
Hematologic No underlying causes
Iatrogenic Abdominal surgery , Endoscopic retrograde cholangiopancreatography, Ischemia from bypass surgery, Reye's syndrome
Infectious Disease Ascaris blocking pancreatic outflow, Campylobacter jejuni, Chinese liver fluke, Coxsackie B virus, Cytomegalovirus, Epstein-Barr virus , HIV-1 disease, Human enterovirus B, Varicella zoster, Mumps, Mycoplasma pneumoniae, Teniasis, Varicella-zoster virus
Musculoskeletal / Ortho No underlying causes
Neurologic No underlying causes
Nutritional / Metabolic Hypercalcaemia, Hyperlipidemia, Hypertriglyceridemia, Lipoprotein lipase deficiency, Apolipoprotein C-II deficiency, Familial hypertriglyceridaemia, Familial partial lipodystrophy type 1
Obstetric/Gynecologic No underlying causes
Oncologic Cholangiocarcinoma, Pancreatic cancer
Opthalmologic No underlying causes
Overdose / Toxicity Asparaginase, Azathioprine, Bexarotene, Bumetanide, Didanosine, Diuretics, Enfuvirtide, Ethanol, Exenatide, Frusemide, Linagliptin, Liraglutide, Mesalazine, Metronidazole, NSAIDS, Olsalazine, Oxyphenbutazone, Sitagliptin, Steroids, Sulfonamides, Thiazide, Valproic acid
Psychiatric No underlying causes
Pulmonary Cystic fibrosis
Renal / Electrolyte No underlying causes
Rheum / Immune / Allergy Autoimmune disease , Polyarteritis nodosa, Sytemic lupus erythematosus
Sexual Cystic fibrosis
Trauma Abdominal trauma , Pancreatic trauma
Urologic No underlying causes
Dental No underlying causes
Miscellaneous Excessive alcohol, Hypothermia, Idiopathic, Repeated marathon running

Causes in Alphabetical Order


References

  1. Yadav D, Lowenfels AB (2006). "Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review". Pancreas. 33 (4): 323–30. doi:10.1097/01.mpa.0000236733.31617.52. PMID 17079934.
  2. Yadav D, Lowenfels AB (2006). "Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review". Pancreas. 33 (4): 323–30. doi:10.1097/01.mpa.0000236733.31617.52. PMID 17079934.
  3. Coté GA, Imperiale TF, Schmidt SE, Fogel E, Lehman G, McHenry L; et al. (2012). "Similar efficacies of biliary, with or without pancreatic, sphincterotomy in treatment of idiopathic recurrent acute pancreatitis". Gastroenterology. 143 (6): 1502–1509.e1. doi:10.1053/j.gastro.2012.09.006. PMID 22982183.
  4. DiMagno MJ, Dimagno EP (2012). "Pancreas divisum does not cause pancreatitis, but associates with CFTR mutations". Am J Gastroenterol. 107 (2): 318–20. doi:10.1038/ajg.2011.430. PMC 3458421. PMID 22306946.
  5. Coté GA, Yadav D, Slivka A, Hawes RH, Anderson MA, Burton FR; et al. (2011). "Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis". Clin Gastroenterol Hepatol. 9 (3): 266–73, quiz e27. doi:10.1016/j.cgh.2010.10.015. PMC 3043170. PMID 21029787.
  6. Bertilsson S, Kalaitzakis E (2015). "Acute Pancreatitis and Use of Pancreatitis-Associated Drugs: A 10-Year Population-Based Cohort Study". Pancreas. 44 (7): 1096–104. doi:10.1097/MPA.0000000000000406. PMID 26335010.
  7. Whitcomb DC (2013). "Genetic risk factors for pancreatic disorders". Gastroenterology. 144 (6): 1292–302. doi:10.1053/j.gastro.2013.01.069. PMC 3684061. PMID 23622139.
  8. 8.0 8.1 "JAMA Network | JAMA Internal Medicine | Glucagonlike Peptide 1–Based Therapies and Risk of Hospitalization for Acute Pancreatitis in Type 2 Diabetes MellitusA Population-Based Matched Case-Control StudyGLP-1 and the Risk of Acute Pancreatitis". Retrieved 2013-02-26.

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