Pancreatitis, Autoimmune - Autoimmune Pancreatitis


Indications for Testing

Criteria for Diagnosis

  • Currently, no consensus diagnostic criteria for AIP has been established; however, several groups have outlined useful diagnostic criteria  
    • Diagnostic criteria for autoimmune pancreatitis by the Japan Pancreas Society (Okazaki, 2010)
      JPS Diagnostic Criteria for Autoimmune Pancreatitis

      Findings on imaging radiography (one 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 (one required)

      • Serologic analysis
        • Elevated serum IgG4 level
        • Elevated serum IgG or gammaglobulin level
        • Presence of antilactoferrin antibody (ALA), anti-carbonic anhydrase II antibody (ACA II), anti-smooth muscle antibody (ASMA), or antinuclear antibody (ANA)
      • Pancreatic-biliary histologic analysis
        • Periductal lymphoplasmacytic infiltration or fibrosis
        • Obliterative phlebitis
        • IgG4-positive plasma cells in tissue*
      • Nongastrointestinal histologic analysis
        • Tubulointerstitial nephritis with immune deposits within tubular basement membranes
        • Pulmonary interstitial lymphoplasmacytic infiltration with IgG4-positive plasma cells*
        • 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)

      Kim Diagnostic Criteria for Autoimmune Pancreatitis

      Diagnostic Criteria

      • 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

      For diagnosis, criterion I must be present, together with any of criteria II to IV

      HISORt diagnostic criteria for autoimmune pancreatitis (Chari, 2007)

      HISORt Diagnostic Criteria for Autoimmune Pancreatitis



      A. Histology

      Diagnostic (any one)

      • Pancreatic histology showing lymphoplasmacytic sclerosing pancreatitis (LPSP)
      • Lymphoplasmacytic infiltrate with abundant (>10 cells/HPF) IgG4-positive cells in pancreas

      Supportive (any one)

      • 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
      CT: computed tomography; MRI: magnetic resonance imaging; ERCP: endoscopic retrograde cholangiopancreatography; HPF: high power field
      Diagnostic criteria for autoimmune pancreatitis by the Italian Group (Ikeura, 2013)
      Diagnostic Criteria for Autoimmune Pancreatitis by Italian Group
      • Histology and cytology
        • Dense lymphocyte infiltration and destruction of the exocrine glands, “destructive pancreatitis” on histology or rich inflammatory cells on cytology
      • The association with other postulated autoimmune disease
      • Response to the steroid therapy
  • Although significant differences exist among these criteria, overlaps occur in certain aspects
    • The most comprehensive diagnostic criteria for AIP is from the JPS and requires imaging plus laboratory and/or histopathologic findings

Laboratory Testing

  • Initial testing – IgG4, CA19-9, liver enzymes, CBC, amylase and lipase
    • Marked elevation of any of these tests is rare except for IgG4
      • ≥2-fold elevation of IgG4 highly suggestive of AIP
      • IgG4 elevated in <50% of U.S./European patients
    • CA19-9 – elevated in 50% of patients with AIP and does not necessarily indicate malignancy
  • Nonspecific autoantibody testing – most often positive in type 1
    • Nonspecific testing may have already been performed
    • ANA – positive in >50%
    • RF, anti SS-A, anti SS-B, AMA – positive in ~20%
    • ALA, ACA, ASMA
      • Sensitivity of these markers is unknown


  • Characterized by lymphocyte and plasma cell infiltration

Imaging Studies

  • Ultrasound/CT/MRI – typically shows diffuse enlargement of the pancreas (sausage shape)

Differential Diagnosis

Clinical Background

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis characterized by diffuse enlargement of the pancreas, narrowing of the pancreatic duct, lymphoplasmacytic infiltration and fibrosis, and increased serum IgG4. It is currently classified as an IgG4-related disease.


  • Incidence – rare, <1/100,000 (including Japan)
  • Age
    • Type 1 – usually 60s
    • Type 2 – usually 50s
  • Sex
    • Type 1 – M>F; 2-3:1
    • Type 2 – M:F, equal


  • Type 1 – elevated IgG4-associated systemic disease (bile duct, salivary gland, lymph nodes, kidneys, retroperitoneum)
  • Type 2 – not associated with elevated IgG4; systemic organ disease includes only inflammatory bowel disease to this point


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

Clinical Presentation

  • Constitutional symptoms – weight loss, fatigue
  • Pancreatic symptoms
    • Obstructive jaundice
    • Abdominal pain
    • Diabetes
  • Type 1 frequently coexists with another autoimmune disease (eg, chronic sclerosing sialoadenitis, primary sclerosing cholangitis, or primary biliary cirrhosis)
  • Extrapancreatic
    • Pulmonary – solid nodular, alveolar interstitial, ground glass opacities, bronchovascular
    • Renal – tubulointerstitial nephritis most common
    • Gastrointestinal – sclerosing cholangitis, retroperitoneal fibrosis
    • Salivary glands – chronic sclerosing sialadenitis

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
Test Name and Number Recommended Use Limitations Follow Up
Amylase, Serum or Plasma 0020013
Method: Quantitative Enzymatic
Evaluate for presence of pancreatitis     
Lipase, Serum or Plasma 0020014
Method: Quantitative Enzymatic
Evaluate for presence of pancreatitis     
Aspartate Aminotransferase, Serum or Plasma 0020007
Method: Quantitative Enzymatic
Evaluate liver function     
Alanine Aminotransferase, Serum or Plasma 0020008
Method: Quantitative Enzymatic
Evaluate liver function     
Immunoglobulin G Subclass 4 0050576
Method: Quantitative Nephelometry

Aid in diagnosis of autoimmune pancreatitis

Elevated IgG4 must be interpreted in conjunction with clinical, histopathologic and radiographic findings

IgG4 levels decline with resolution of inflammation

Cancer Antigen-GI (CA 19-9), Body Fluid 0020746
Method: Quantitative Electrochemiluminescent Immunoassay

Screening for pancreatic cancer when evidence of pancreatic disease exists

Immunoglobulin G4 by Immunohistochemistry 2005844
Method: Immunohistochemistry

Aid in diagnosing autoimmune pancreatitis

Stained and returned to client pathologist for interpretation; consultation available if needed

Additional Tests Available
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
CBC with Platelet Count 0040002
Method: Automated Cell Count

Evaluate for presence of infection

Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflex to ANA, IgG by IFA 0050080
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Aids in initial diagnosis of connective tissue disease

Reflex pattern – if ANA are detected by ELISA, then ANA by IFA titer will be added

ANA ELISA screen is designed to detect antibodies against dsDNA, histone, SS-A (Ro), SS-B (La), Smith, snRNP/Sm, Scl-70, Jo-1, centromere, and an extract of lysed HEp-2 cells

ANA ELISA assays have been reported to have lower sensitivities for antibodies associated with nucleolar and specked ANA-IFA patterns

Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflexes to ANA, IgG by IFA and to dsDNA, RNP, Smith, SSA 52, SSA 60, and SSB Antibodies, IgG 0050317
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Aids in initial diagnosis of connective tissue disease

Reflex pattern – if ANA IgG is detected by ELISA, then ANA IgG by IFA (using HEp-2 substrate) will be added; if ANA, IgG by IFA is confirmed positive with a titer of 1:40 or greater, then a titer and pattern will be reported; in addition, samples positive for ANA, IgG by IFA will reflex to double-stranded DNA (dsDNA) antibody, IgG by ELISA, RNP (U1) (Ribonucleic Protein) (ENA) antibody, IgG, Smith (ENA) antibody, IgG, SSA 52 and 60 (Ro) (ENA) antibodies, IgG, and SSB (La) (ENA) antibody, IgG. If double-stranded DNA (dsDNA) antibody, IgG by ELISA is detected, then double-stranded DNA (dsDNA) antibody, IgG by IFA (using Crithidia luciliae) will be added

Rheumatoid Factors, IgA, IgG, and IgM by ELISA 0051298
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Quantitative Enzyme-Linked Immunosorbent Assay.

May aid in prognostication for rheumatoid arthritis

Rheumatoid arthritis panel is preferred for the workup of suspected rheumatoid arthritis or undifferentiated inflammatory arthritides

Mitochondrial M2 Antibody, IgG (ELISA) 0050065
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Differentiate AIP from PBC

F-Actin (Smooth Muscle) Antibody, IgG 0055248
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

F-actin antibodies have greater sensitivity and specificity for autoimmune disease than anti-smooth muscle antibodies