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 (PRSS1, CFTR, SPINK1) if patient has
    • Recurrent, unexplained attacks of acute pancreatitis and positive family history
    • Unexplained chronic pancreatitis and positive family history
    • Unexplained chronic pancreatitis without positive family history 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.

There are several causes of chronic pancreatitis

  • Alcohol – most common (80% of cases)
  • Idiopathic – ~20% of cases
  • Hereditary – rare genetic condition manifesting at early age

Epidemiology

  • Incidence – 3.5-10/100,000 (Europe and U.S.)
  • Age – 30-40 years in chronic forms; 10-20 years in hereditary forms

Risk Factors

Genetics (Hereditary and Idiopathic)

  • Hereditary chronic pancreatitis (HCP) – autosomal dominant disease with variable expression caused by mutations in the PRSS1 (trypsin 1) gene
    • HCP cannot be clinically distinguished from other forms of chronic pancreatitis
  • Two most common PRSS1 gene mutations (R122H and N29I) – reported to have a penetrance of 80% for hereditary pancreatitis
    • De novo PRSS1 mutations found in 10% of idiopathic chronic pancreatitis patients of all ages (as many as 35% of those <25 years)
  • Serine peptidase inhibitor Kazal type 1 (SPINK1) and cystic fibrosis transmembrane regulator (CFTR) genes are risk factors for pancreatitis
    • CFTR and SPINK1 inherited in autosomal recessive or multifactorial fashion
    • CFTR 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 mutations
      • 15% of individuals with idiopathic pancreatitis have SPINK1 mutations
      • ~25% of children with idiopathic pancreatitis have SPINK1 mutations
      • Mutation N24S increases the risk for pancreatitis 14-fold
      • Mutations do not appear to be increased in individuals with hereditary pancreatitis
      • Mutations do not influence disease severity

Pathophysiology

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

Clinical Presentation

  • Recurrent episodes of acute pancreatitis – often presenting in childhood and progressing 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 resulting 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, Hereditary (PRSS1) Sequencing 2002016
Method: Polymerase Chain Reaction/Sequencing

Order in children with pancreatitis or in affected adults with positive family history

Clinical sensitivity 80%

Rare diagnostic errors can occur due to primer site mutations

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

 
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

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

Order in adults with idiopathic pancreatitis if other components of panel have already been performed (eg, CFTR and PRSS1 sequencing)

(See cystic fibrosis topic for full CFTR test recommendations)

Clinical sensitivity 17%

Rare diagnostic errors can occur due to primer site mutations

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

Mutations in CFTR and PRSS1 will not be detected

 
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
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, potasium, 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