Pancreatitis, Chronic - Chronic Pancreatitis

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Recurrent episodes of pancreatitis
  • Pancreatitis at early age

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

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.) (Copenhagen study)
  • 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 present in childhood and progress 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
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.

Pancreatic Elastase, Fecal 0080526
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Limitations 

Limited sensitivity in patients with mild to moderate chronic pancreatitis

Chymotrypsin, Fecal 2005160
Method: Quantitative Enzymatic/Spectrophotometry

Limitations 

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

Limitations 

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

General References

Braganza JM, Lee SH, McCloy RF, McMahon MJ. Chronic pancreatitis. Lancet. 2011; 377(9772): 1184-97. PubMed

Chen J, Férec C. Chronic pancreatitis: genetics and pathogenesis. Annu Rev Genomics Hum Genet. 2009; 10: 63-87. PubMed

Espinoza GM, Prost A. Cogan's syndrome and other ocular vasculitides Curr Rheumatol Rep. 2015; 17(4): 24. PubMed

Rosendahl J, Bödeker H, Mössner J, Teich N. Hereditary chronic pancreatitis. Orphanet J Rare Dis. 2007; 2: 1. PubMed

Teich N, Mössner J. Hereditary chronic pancreatitis. Best Pract Res Clin Gastroenterol. 2008; 22(1): 115-30. PubMed

Whitcomb DC. Genetic aspects of pancreatitis. Annu Rev Med. 2010; 61: 413-24. PubMed

Witt H. Genetics of pancreatitis: a guide for clinicians. Dig Dis. 2010; 28(6): 702-8. PubMed

Medical Reviewers

Last Update: September 2016