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, Idiopathic (CFTR, PRSS1, SPINK1) Sequencing 2002005
Method: Polymerase Chain Reaction/Sequencing

Order in idiopathic recurrent pancreatitis to determine genetic predisposition to condition

Clinical sensitivity – 45%

Rare diagnostic errors can occur due to primer site mutations

Regulatory region mutations, deep intronic mutations, and large deletions/duplications will not be detected

 
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

For adults with idiopathic pancreatitis if other components of the panel (CFTR, PRSS1, and SPINKK1) have been sequenced without providing a complete explanation for the pancreatitis

Pancreatitis, Hereditary (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, Idiopathic (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