Pancreatitis, Chronic

Diagnosis

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 (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

• Alcohol abuse
• Autoimmune pancreatitis
• Biliary obstruction
• Gallbladder stone disease
• Hereditary hyperparathyroidism
• Familial hypocalciuric hypercalcemia
• Inflammatory bowel disease
• Pancreatic cancer
• Peptic ulcer disease

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

• Heavy alcohol use
• Hereditary disorders of the pancreas
  • Cystic fibrosis – most common inherited disorder leading to chronic pancreatitis
• Hypercalcemia
• Hyperlipidemia
• Chronic renal failure
• Autoimmune disease – Sjögren syndrome, inflammatory bowel disease, primary biliary cirrhosis
• Medications – valproate, phenacetin, thiazides, estrogens, azathioprine
• Miscellaneous – gall stones, transplantation, vascular disease

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
  • Increased risk of pancreatic cancer – up to 40% lifetime risk

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

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
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