Overview
Epidemiology
- Epidemiologic data are limited due to varying diagnostic criteria for the disease.
- Incidence: 5–12 per 100,000 people
- Alcohol-related disease more common in Western countries and Japan:
- Associated with over half of all cases in the United States
- < 5% of heavy drinkers develop chronic pancreatitis.
- Potential cofactors include diet, genetic background, ancestry, type of alcohol, and smoking.
- Predominantly idiopathic in women
Etiology
Common etiologies of chronic pancreatitis are summarized with the “TIGAR-O” mnemonic:
| T | Toxic/metabolic |
|
|---|---|---|
| I | Idiopathic | May be early- or late-onset |
| G | Genetic mutations |
|
| A | Autoimmune |
|
| R | Recurrent acute pancreatitis | The strongest risk factor for developing chronic pancreatitis |
| O | Obstructive |
|
Gene abbreviations:
PRSS1 → cationic trypsinogen:
- Gain-of-function mutation resulting in abnormal trypsin
- Activates digestive enzymes in the pancreas
- Leads to ongoing damage
CFTR → cystic fibrosis transmembrane conductance regulator gene:
- Modifier gene that increases susceptibility to chronic pancreatitis and accelerates progression
- Multiple types of mutations result in different effects on exocrine function
SPINK1 → pancreatic secretory trypsin inhibitor gene:
- Responsible for inhibiting prematurely activated intra-pancreatic trypsin
Pathophysiology
- Mechanism is not well understood.
- 3 proposed theories (result in a loss of acinar, islet, and ductal cell function within the pancreas):
- Acinar cells secrete more proteins, but ductal epithelial cells produce less fluid and bicarbonate → results in viscous fluid → proteins obstruct pancreatic ducts → persistent inflammation → fibrosis, ductal strictures, and atrophy
- Repeated injury from acute pancreatitis → inflammation and necrosis → pancreatic stellate cells activated → fibrosis
- Toxins and genetic factors allow for premature activation of digestive enzymes (trypsin) → auto-digestive injury to glandular tissue
- Pancreatic damage leads to:
- Calcifications
- Exocrine insufficiency
- Decreased lipase, amylase, and protease
- Results in malabsorption and maldigestion
- Endocrine insufficiency
- Destruction of β cells
- Results in decreased insulin production
- Dysplasia and malignancy
Flowchart summarizing how insults to the pancreas lead to pancreatic insufficiency. Note that injury leads to the activation of pancreatic stellate cells and digestive enzymes, resulting in damaged pancreatic tissue, inflammation, fibrosis, and the loss of exocrine and endocrine cell function.
Image by Lecturio.Clinical Presentation
Clinical manifestations
- Recurrent abdominal pain
- Intermittent or constant, severe epigastric pain
- Radiates to the back or in band-like fashion across the abdomen
- May be exacerbated with meals
- Does not necessarily correlate with the severity of changes on imaging
- Nausea and vomiting
- Steatorrhea
- Oily, foul-smelling, and floating stools
- Due to maldigestion of fat
- Weight loss (due to steatorrhea or fear of eating due to pain)
- Rarely, patients may be asymptomatic.
Physical exam
- Signs of malnutrition:
- Decreased subcutaneous fat
- Temporal wasting
- Epigastric abdominal tenderness
Diagnosis
Imaging
- Abdominal computed tomography (CT): best initial test
- Findings:
- Parenchymal and intraductal calcifications
- Pancreatic atrophy
- Dilated pancreatic ducts
- Low sensitivity in patients with early disease
- Findings:
- Magnetic resonance imaging with cholangiopancreatography (MRCP)
- Indicated when CT findings are equivocal, but may be non-diagnostic in early disease
- Findings:
- Ductal strictures and dilations giving a “chain of lakes” or “string of pearls” appearance
- Pancreatic calcifications
- Secretin can be used to help identify subtle changes.
- Endoscopic ultrasound (EUS)
- Used if CT and MRI are not diagnostic but there is a high index of suspicion
- Can detect early disease
- Non-specific, and changes can be seen in other patient populations
- Parenchymal abnormalities:
- Hyperechoic foci and stranding
- Lobular contour
- Cysts
- Ductal abnormalities:
- Main duct dilation
- Hyperechoic margins
- Stones
- Endoscopic retrograde cholangiopancreatography (ERCP)
- Not used for diagnosis
- Does not evaluate the parenchyma
- Invasive and expensive
- Reserved for stone removal and stent placement (pancreatic duct structures)
- Not used for diagnosis
Laboratory testing
Laboratory testing is used as an adjunct to imaging.
- Amylase and lipase
- May be elevated, but usually normal in the later stages (due to atrophy and fibrosis of the pancreas → decreased enzyme production)
- No diagnostic value
- Liver function tests: ↑ bilirubin and alkaline phosphatase → pancreatic obstruction
- Triglycerides: fasting level > 1,000 is associated with pancreatitis
- Fecal evaluations
- ↑ 72-hour fecal fat measurement
- ↓ fecal chymotripsin
- Rare diagnostic evaluations:
- ↑ IgG4 → autoimmune pancreatitis
- Genetic testing (for young patients and those with a strong family history)
- Pancreatic function tests
- Can detect early disease, but are expensive and invasive
- Direct function testing: exogenous secretin and cholecystokinin are injected → stimulation of the pancreas → duodenal or pancreatic aspirates are measured for bicarbonate, protease, amylase, and lipase
- Indirect function testing: measurements of chymotrypsin and elastase in fecal samples → exocrine insufficiency
A 50-year-old woman with autoimmune chronic pancreatitis. Endoscopic ultrasound image arrows showing (a) common bile duct stricture, (b) dilated common hepatic duct, (c) reactive lymph node, and (d) homogenous pancreatic body.
Image: “fig2” by Lahey Clinic, Burlington, MA 01805, USA. License: CC BY 3.0
A 50-year-old woman with autoimmune chronic pancreatitis. Arrows in ERCP show common bile duct and main pancreatic duct strictures pre-stent insertion (a and b) and post-stent insertion (c and d).
Image: “fig3” by Lahey Clinic, Burlington, MA 01805, USA. License: CC BY 3.0
Abdominal CT scan showing pancreatic calcifications in chronic pancreatitis (green arrows)
Image: “CT Abdomen” by Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, BDB 380, USA. License: CC BY 3.0
Management
- Lifestyle changes
- Abstinence from alcohol and smoking
- Small, frequent, low-fat meals
- Adequate hydration
- Supplementation of fat-soluble vitamins (A, D, E, K)
- Pancreatic insufficiency management
- Endocrine insufficiency: insulin
- Exocrine insufficiency: pancreatic enzyme replacement
- Pain treatment
- Medications:
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Tricyclic antidepressants
- Long-acting opiates for severe pain
- Invasive measures for intractable pain:
- Celiac nerve block
- ERCP for decompression of blocked pancreatic ducts
- Extracorporeal shock wave lithotripsy of pancreatic stones
- Medications:
- Surgery
- Reserved for patients who fail medical therapy or are suspected to have pancreatic cancer
- Type of surgery depends on the pancreatic duct anatomy, patient’s history, and complications:
- Resection
- Decompression
Complications
- Metabolic:
- Osteopenia and osteoporosis
- Fat-soluble vitamin deficiencies (A, D, E, K)
- Pancreatic diabetes
- Structural:
- Pancreatic pseudocyst formation (encapsulated collection of fluid)
- Usually self-resolves, but may be complicated by infection or rupture
- Can be drained if > 5 cm or symptomatic
- Bile duct and duodenal obstruction from direct compression from a pseudocyst
- Pseudoaneurysm develops when there is erosion of an artery into a pseudocyst (potentially life-threatening!)
- Pancreatic ascites due to disruption of the pancreatic duct
- Pancreatic pseudocyst formation (encapsulated collection of fluid)
- Inflammatory:
- Splenic or portal vein thrombosis due to inflammation surrounding the veins
- Pancreatic ductal adenocarcinoma from chronic inflammation (higher risk in hereditary forms of pancreatitis)
Differential Diagnosis
- Cholelithiasis: presence of gallstones within the gallbladder. May be asymptomatic or present with colicky right upper quadrant abdominal pain, nausea, and vomiting. Biliary tract stones are visualized by ultrasound or CT. Treatment involves diet modification, pain control, and cholecystectomy for symptomatic individuals. Symptoms and imaging will differentiate this condition from chronic pancreatitis.
- Perforation of the intestine: injury of the bowel wall, resulting in subsequent release of gastrointestinal contents into the peritoneum. Patients may present with acute chest or abdominal pain and display evidence of peritonitis. Computed tomography will show extraluminal gas. Management usually involves antibiotics and surgery. Physical exam and imaging will differentiate this condition from chronic pancreatitis.
- Chronic mesenteric ischemia: caused by inadequate blood flow through the mesenteric vessels, resulting in ischemia of the bowel wall. Patients present with episodic, postprandial abdominal pain, and may lose weight due to food aversion. Computed tomography angiography is used for diagnosis, and treatment may include conservative measures or revascularization. Imaging will differentiate this condition from chronic pancreatitis.
- Peptic ulcer disease: a gastric (or duodenal) mucosal defect resulting from gastric acid hypersecretion or impaired bicarbonate secretion. Patients may have dyspepsia, postprandial pain, early satiety, nausea, or evidence of bleeding. Diagnosis is made with upper endoscopy. Management includes lifestyle changes, Helicobacter pylori treatment, and proton pump inhibitors. The history and endoscopic findings will differentiate this condition from chronic pancreatitis.
- Pancreatic cancer: a malignancy of the pancreas tissue. Patients may be asymptomatic at first, but can later develop vague, chronic epigastric pain; weight loss; steatorrhea; and jaundice. Diagnosis is made with abdominal imaging, biopsy, and tumor markers. Treatment depends on the cancer type and staging. Chronic pancreatitis patients (particularly those with hereditary forms) are at risk for pancreatic cancer.
References
- Forsmark, C.E., Freeman, S.D., and Lewis, M.D. (2020). Etiology and pathogenesis of chronic pancreatitis in adults. In Grover, S. (Ed.), Uptodate. Retrieved October 27, 2020, from https://www.uptodate.com/contents/etiology-and-pathogenesis-of-chronic-pancreatitis-in-adults
- Freedman, S.D., Forsmark, C.E. (2020). Chronic pancreatitis: Clinical manifestations and diagnosis in adults. In Grover, S. (Ed.), Uptodate. Retrieved October 27, 2020, from https://www.uptodate.com/contents/chronic-pancreatitis-clinical-manifestations-and-diagnosis-in-adults
Freedman, S.D. (2018). Treatment of chronic pancreatitis. In Grover, S. (Ed.), Uptodate. Retrieved October 28, 2020, from https://www.uptodate.com/contents/treatment-of-chronic-pancreatitis - Huffman, J.L., Obideen, K., and Wehbi, M. (2019). Chronic pancreatitis. In Andad, B.S. (Ed.), Medscape. Retrieved October 27, 2020, from https://emedicine.medscape.com/article/181554-overview#a5
- Brock, C., Nielsen, L. M., Lelic, D., & Drewes, A. M. (2013). Pathophysiology of chronic pancreatitis. World Journal of Gastroenterology, 19(42), 7231–7240. https://doi.org/10.3748/wjg.v19.i42.7231
- Kasper, D.L., Fauci, A.S., Longo, D.L., Bruanwald, E., Hauser, S.L., and Jameson, J.L. (2007). Harrison’s principles of internal medicine (16th edition.). New York: McGraw Hill Education.
