Autoimmune Pancreatitis

Diagnosis

Indications for Testing

• Painless obstructive jaundice
• Chronic or recurrent abdominal pain
• Pancreatic mass
• Decrease in pancreatic function resulting in hyperglycemia or steatorrhea
• Acute pancreatitis

Criteria for Diagnosis

• Several diagnostic criteria have been developed, relying primarily on imaging and histology, and incorporating additional information about other organs involved and response to steroids
  • Serum IgG4 elevations – helpful in diagnosis of type 1 AIP (~66% will have elevations)
    • Not helpful for type 2 AIP (only ~25% have elevated serum IgG4)
  • Although significant differences exist among these criteria, overlaps occur in certain aspects
• The most comprehensive diagnostic criteria for AIP is from the new international consensus – requires imaging plus laboratory and/or histopathologic findings
  • HISORt (histology, imaging, serology, other organ involvement, and response to therapy) diagnostic criteria for autoimmune pancreatitis (Chari, 2006)

    HISORt Diagnostic Criteria for Autoimmune Pancreatitis

    Group	Criteria
    A. Histology	Diagnostic (any 1) Pancreatic histology showing LPSP Lymphoplasmacytic infiltrate with abundant (>10 cells/HPF) IgG4-positive cells in pancreas Supportive (any 1) Lymphoplasmacytic infiltrate with abundant (>10 cells/HPF) IgG4-positive cells in involved extrapancreatic organ Lymphoplasmacytic infiltrate with fibrosis in pancreas
    B. Imaging	Typical imaging features CT/MRI – diffusely enlarged gland with delayed (rim) enhancement ERCP – diffusely irregular and attenuated main pancreatic duct Atypical imaging features Pancreatitis, focal pancreatic mass, focal pancreatic duct stricture, pancreatic atrophy, pancreatic calcification
    C. Serology	Elevated serum IgG4 level
    D. Other organ involvement	Hilar/intrahepatic biliary strictures, persistent distal biliary stricture, parotid/lacrimal gland involvement, mediastinal lymphadenopathy, retroperitoneal fibrosis
    E. Response to steroid therapy	Resolution/marked improvement of pancreatic/extrapancreatic manifestation with steroid therapy
    F. Diagnosis	Group A, diagnostic histology alone Group B, typical imaging features and elevated serum IgG4 Group C, unexplained pancreatic disease with serology or other organ involvement and response to steroid
    Source: Chari, 2006 CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; HPF, high power field; LPSP, lymphoplasmacytic sclerosing pancreatitis; MRI, magnetic resonance imaging

  • Diagnostic criteria for autoimmune pancreatitis by the Japan Pancreas Society (Okazaki, 2009)

    • Findings on imaging radiography (1 required)
      • Cross-sectional imaging
        • Diffusely enlarged pancreas
        • Enhanced peripheral rim of hypoattenuation “halo”
        • Low-attenuation mass in head of pancreas
      • Endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP)
        • Segmental pancreatic ductal narrowing
        • Focal pancreatic ductal narrowing
        • Diffuse pancreatic ductal narrowing
    • Serologic and histologic findings (1 required)
      • Serologic analysis
        • Elevated serum IgG4 level
        • Elevated serum IgG or gammaglobulin level
        • Presence of antilactoferrin antibody (ALA), anticarbonic anhydrase II antibody (ACA II), antismooth muscle antibody (ASMA), or antinuclear antibody (ANA)
      • Pancreatic-biliary histologic analysis
        • Periductal lymphoplasmacytic infiltration or fibrosis
        • Obliterative phlebitis
        • IgG4-positive plasma cells in tissue (the presence of tissue IgG4-positive cells is not necessarily abnormal, but an increased number of infiltrating IgG4-positive plasma cells is abnormal)
      • Nongastrointestinal histologic analysis
        • Tubulointerstitial nephritis with immune deposits within tubular basement membranes
        • Pulmonary interstitial lymphoplasmacytic infiltration with IgG4-positive plasma cells (the presence of tissue IgG4-positive cells is not necessarily abnormal, but an increased number of infiltrating IgG4-positive plasma cells is abnormal)
        • Chronic sialadenitis with IgG4-positive plasma cells (the presence of tissue IgG4-positive cells is not necessarily abnormal, but an increased number of infiltrating IgG4-positive plasma cells is abnormal)
  • Kim diagnostic criteria for autoimmune pancreatitis (Kim, 2006)
    • For diagnosis, criterion I must be present, together with any of criteria II to IV
    • Criterion I. Pancreatic imaging (essential)
      • Diffuse enlargement of pancreas and
      • Diffuse/segmental irregular narrowing of main pancreatic duct
    • Criterion II. Laboratory finding
      • Elevated levels of IgG or IgG4 or
      • Detected autoantibodies
    • Criterion III. Histopathology
      • Fibrosis and lymphoplasmacytic infiltration
    • Criterion IV. Response to steroid

• Initial testing
  • Liver enzymes
    • May show an obstructive pattern
  • Lipase
    • May be elevated
    • Nonspecific marker for pancreatic damage
  • CBC
    • Useful in evaluation for malignancy
    • Does not provide information for diagnosis of AIP
  • Serum IgG4
    • ≥2-fold elevation of IgG4 highly suggestive of AIP
    • IgG4 elevated in ~66% of patients (Hart, 2015)
  • CA19-9 – elevated in 50% of patients with AIP
    • Also elevated in malignancy, but not specific for malignancy

• Characterized by lymphocyte and plasma cell infiltration
  • Important in differentiating AIP from acute and chronic pancreatitis, lymphoma, and pancreatic cancer

• Endoscopic ultrasound – diffusely irregular and attenuated main pancreatic duct
• Computed tomography (CT)/magnetic resonance imaging (MRI) – typically shows diffuse enlargement of the pancreas (sausage shape)
• Endoscopic retrograde cholangiopancreatography (ECRP)/magnetic resonance cholangiopancreatography (MRCP) – may be necessary for equivocal cases

• Pancreatic cancer
• Cholangiocarcinoma
• ​Idiopathic pancreatitis
• Primary sclerosing cholangitis
• Primary biliary cholangitis

• Prevalence – 0.82/100,000 in Japan (no U.S. or European data available) (Martins, 2017)
• Age (Martins, 2017)
  • Type 1 AIP – mean age 61.4
  • Type 2 AIP – mean age 39.9
• Sex (Martins, 2017)
  • M>F, 3:1

• Type 1 AIP
  • Pancreatic manifestation of immunoglobulin IgG4-related disease, a multiorgan disease
  • LPSP
• Type 2 AIP
  • Pancreas specific disorder not associated with elevated IgG4
  • Idiopathic duct-centric pancreatitis (IDCP)
  • ​May be associated with inflammatory bowel disease, especially ulcerative colitis

• Type 1 AIP
  • Histologic hallmark is collar-like preductal infiltrates composed of lymphocytes and plasma cells termed LPSP
    • Other organs involved – gallbladder, bile ducts, kidney, lung, and salivary glands most common
    • IgG4-positive plasma cells have been identified in some patients
• Type 2 AIP
  • May be focal or diffuse (duct centric)
    • Focal often resembles pancreatic mass (cancer)
  • Histologic hallmark is idiopathic, duct-centric pancreatitis

• Constitutional symptoms – weight loss, fatigue
  • Marked anorexia, cachexia suggest carcinoma
• Pancreatic symptoms
  • Obstructive jaundice – often painless
  • Abdominal pain – not severe
    • Marked pain suggests carcinoma
  • Hyperglycemia
  • Steatorrhea
• Type 2 AIP may have coexisting inflammatory bowel disease
• Type 1 AIP frequently has multiorgan involvement