Chronic pancreatitis is swelling (inflammation) of the pancreas that does not heal and progressively worsens over time, leading to permanent tissue damage.

There are several causes of chronic pancreatitis, including the following:

• Alcohol – most common (80% of cases)
• Idiopathic – nearly 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 diseases – Sjögren syndrome, inflammatory bowel disease, primary biliary cirrhosis most common
• Medications

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 deleterious PRSS1 gene mutations (R122H and N29I) are reported to have a penetrance of 80% for hereditary pancreatitis
  • De novo PRSS1 mutations are also 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) are risk factors for pancreatitis
  • SPINK1 and CFTR may be inherited in an autosomal recessive or multifactorial fashion
  • ~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
  • 15% of individuals with idiopathic pancreatitis have SPINK1 mutations; ~25% of children with idiopathic pancreatitis have SPINK1 mutations
  • SPINK1 mutation N24S increases the risk for pancreatitis 14-fold
  • SPINK1 mutations do not appear to be increased in individuals with hereditary pancreatitis
  • SPINK1 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, which causes acute damage and inflammation to the pancreas
• Chronic recurring release of these enzymes causes permanent damage to the pancreatic exocrine and endocrine functions

Clinical Presentation

• Recurrent bouts of acute pancreatitis, often presenting in childhood and progressing to chronic pancreatitis over time
  • Hereditary pancreatitis is typically 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
• Increased risk of pancreatic cancer (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 Testing

• Recurrent bouts of pancreatitis
• Pancreatitis at an early age

Laboratory Testing

• Pancreatic fecal elastase, fecal chymotrypsin, p-aminobenzoic acid (PABA)
  • Non-invasive; limited sensitivity in patients with mild or moderate chronic pancreatitis
• Consider genetic testing (PRSS1, CFTR, SPINK1) in the following scenarios
  • 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) – use in initial diagnosis but 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
• Familiar hypocalciuric hypercalcemia
• Inflammatory bowel disease
• Pancreatic cancer
• Peptic ulcer disease

Tests generally appear in the order most useful for common clinical situations

General

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• Church NI, Pereira SP, Churchill D, Cairns S, Hatfield AR, Webster GJ. Chronic pancreatitis: diagnosis and management of complications. Gut. 2007; 56 (9) :1189-1190.PubMed
• DiMagno MJ, DiMagno EP. Chronic pancreatitis. Curr Opin Gastroenterol. 2009; 25 (5) :454-459.PubMed
• Keller J, Layer P. Idiopathic chronic pancreatitis. Best Pract Res Clin Gastroenterol. 2008; 22 (1) :105-113.PubMed
• Rosendahl J, Bodeker H, Mossner J, Teich N. Hereditary chronic pancreatitis. Orphanet J Rare Dis. 2007; 2 :1-.PubMed
• Teich N, Mossner J. Hereditary chronic pancreatitis. Best Pract Res Clin Gastroenterol. 2008; 22 (1) :115-130.PubMed
• Thrower E, Husain S, Gorelick F. Molecular basis for pancreatitis. Curr Opin Gastroenterol. 2008; 24 (5) :580-585.PubMed
• Whitcomb DC. Genetic aspects of pancreatitis. Annu Rev Med. 2010; 61 :413-424.PubMed

Pancreatic Cancer
Pancreatitis, Acute