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
    • Noninvasive
    • Limited sensitivity in patients with mild or moderate chronic pancreatitis
  • Consider genetic testing (CFTR, CTRC, PRSS1, SPINK1) 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

  • CT scan, 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 in U.S. (Yadav, 2013)
  • 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 by ELISA 0080526
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Chymotrypsin, Fecal 2005160
Method: Quantitative Enzymatic/Spectrophotometry

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

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

Pedersen T, Andersen N, Pedersen G, Worning H. Chronic pancreatitis in Copenhagen. A retrospective study of 64 consecutive patients Scand J Gastroenterol. 1982; 17(7): 925-31. 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

Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013; 144(6): 1252-61. PubMed

Medical Reviewers

Last Update: July 2017