Pancreatitis, Chronic

Diagnosis

Indications for Testing

Laboratory Testing

  • Nonspecific – elevated glucose, hyperlipidemia, or hypercalcemia (see Acute Pancreatitis)
  • Pancreatic fecal elastase, fecal chymotrypsin
    • Non-invasive; limited sensitivity in patients with mild or moderate chronic pancreatitis
  • Consider genetic testing (CFTR, CTRC, PRSS1) if patient has
    • Recurrent, unexplained attacks of acute pancreatitis and family history of pancreatitis
    • Unexplained chronic pancreatitis and family history of pancreatitis
    • Unexplained chronic pancreatitis without family history of pancreatitis, after exclusion of other causes
    • Unexplained pancreatitis episode in children

Imaging Studies

  • Computed tomography (CT) scan, magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP) – used in initial diagnosis; may not be useful in early onset chronic pancreatitis
    • Positive test demonstrates ductal alterations and calcifications
  • If the above tests are negative and high suspicion exists, perform endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasound
  • Consider functional testing – secretin or pancreozymin-secretin

Differential Diagnosis

Clinical Background

Chronic pancreatitis is a progressive, inflammatory disorder in which pancreatic tissue is permanently lost, leading to malnutrition and diabetes.  Causes of chronic pancreatitis include:

  • Alcohol abuse – most common (~75% of cases)
  • Hereditary (eg, cystic fibrosis) – least common
  • idiopathic – ~20% of cases

Epidemiology

  • Incidence – 8/100,000 (Europe and U.S.)
  • Age – 30-40 years in chronic form; 10-20 years in hereditary form

Risk Factors

Genetics (Hereditary and Idiopathic)

  • Hereditary chronic pancreatitis (HCP) – autosomal dominant disease with variable expression caused by mutations in the protease, serine, 1 (trypsin 1, cationic trypsinogen) (PRSS1) gene
    • HCP cannot be clinically distinguished from other forms of chronic pancreatitis
  • PRSS1 (R122H and N29I) gene mutations
    • Penetrance of 80% for hereditary pancreatitis
    • De novo PRSS1 gene mutations found in 10% of idiopathic chronic pancreatitis patients of all ages (as many as 35% of those <25 years)
  • Serine protease inhibitor, Kazal type 1 (SPINK1) and cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7) ABCC7 (CFTR) genes are risk factors for pancreatitis
    • Chymotrypsin C (caldecrin) (CTRC), CFTR, SPINK1 gene mutations inheritance –  autosomal recessive
    • CFTR gene mutations
      • ~30% of individuals with idiopathic pancreatitis have at least one CFTR mutation
      • The presence of two CFTR mutations increases the risk for idiopathic pancreatitis 40-fold
    • SPINK1 gene mutations
      • ~15% of adults with idiopathic pancreatitis have SPINK1 gene mutation(s)
      • ~25% of children with idiopathic pancreatitis have SPINK1 gene mutation(s)
      • Mutation N24S increases the risk for pancreatitis 14-fold
    • CTRC gene mutations
      • ~4% of individuals with idiopathic pancreatitis have CTRC gene mutation(s)

Pathophysiology

  • Exocrine pancreas cells produce digestive enzymes in the inactive form (eg, trypsinogen); these are converted to the active form (eg, trypsin) after reaching the duodenum
  • Pancreatitis leads to the initial release of these enzymes in the active form, causing acute pancreatic damage and inflammation
  • Chronic recurring release of these enzymes causes permanent damage to the exocrine and endocrine functions of the pancreas

Clinical Presentation

  • Recurrent episodes of acute pancreatitis often presents in childhood and progresses to chronic pancreatitis
    • Hereditary pancreatitis – indistinguishable from other forms of chronic pancreatitis  
  • Abdominal pain, nausea, vomiting, weight loss, diarrhea, and oily stools
  • Advanced stages
    • Pain often decreases
    • Malabsorption, diabetes
    • Local complications – pseudocyst formation, biliary and duodenal obstruction, pseudoaneurysm
  • Complications

Treatment

  • Dependent on symptoms
  • Primary
    • Pain control
    • Enzyme supplements/replacement
    • Rehydration
  • Severe cases
    • Surgery for pseudocysts and biliary or duodenal obstruction
    • Removal of pancreas – usually results in permanent, insulin-dependent diabetes

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Pancreatic Elastase, Fecal 0080526
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Screen for exocrine insufficiency in patients with suspected pancreatic disease

Non-invasive test of choice for measuring pancreatic exocrine function

Limited sensitivity in patients with mild to moderate chronic pancreatitis

 
Chymotrypsin, Fecal 2005160
Method: Quantitative Enzymatic/Spectrophotometry
Screen for exocrine insufficiency in patients with suspected pancreatic disease

Patients receiving pancreatic enzymes should discontinue taking the enzymes at least 5 days prior to stool collection

 
Pancreatitis, Panel (CFTR, CTRC, PRSS1, SPINK1) Sequencing 2010876
Method: Polymerase Chain Reaction/Sequencing

Preferred test for individual with history of idiopathic pancreatitis

Clinical sensitivity –  ~50%

Analytical sensitivity –  99%

Regulatory and promoter regions, deep intronic mutations, and large deletions/duplications are not detected

Diagnostic errors can occur due to rare sequence variations

Mutations in currently unknown genes maybe be associated with pancreatitis

 
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Pancreatitis (CTRC) Sequencing 2010703
Method: Polymerase Chain Reaction/Sequencing
Preferred test for individual with history of idiopathic pancreatitis
Clinical sensitivity –  ~50%
Analytical sensitivity –  99%
Pancreatitis (PRSS1) Sequencing 2002016
Method: Polymerase Chain Reaction/Sequencing

Preferred test for individuals with idiopathic pancreatitis who are <20 years of age OR those with two affected first-degree relatives

Pancreatitis (SPINK1) Sequencing 2002012
Method: Polymerase Chain Reaction/Sequencing

For adults with idiopathic pancreatitis if other components of panel (CFTR, CTRC, and PRSS1) have been sequenced without providing a complete explanation for the pancreatitis

Cystic Fibrosis (CFTR) Sequencing 0051110
Method: Polymerase Chain Reaction/Sequencing

May be used to test for mutations causative for mild cystic fibrosis in individuals who present with idiopathic pancreatitis

Amylase, Serum or Plasma 0020013
Method: Quantitative Enzymatic

Aids in diagnosis/prognosis of acute pancreatitis

Lipase, Serum or Plasma 0020014
Method: Quantitative Enzymatic

Prognosis only

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Prognosis only

Comprehensive Metabolic Panel 0020408
Method: Quantitative Ion-Selective Electrode/Quantitative Enzymatic/Quantitative Spectrophotometry

Prognosis only; panel includes albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin, calcium, carbon dioxide, creatinine, chloride, glucose, potassium, protein, sodium, urea nitrogen

Trypsin-Like Immunoreactivity 0070003
Method: Quantitative Radioimmunoassay

Results should be correlated with clinical presentation and other diagnostic data

Macroamylase Determination 2004464
Method: Quantitative Ultrafiltration/Quantitative Enzymatic
Lipid Panel 0020421
Method: Quantitative Enzymatic