Pancreatitis, Autoimmune - Autoimmune Pancreatitis

Primary Author: Ashwood, Edward R., MD.
  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

Criteria for Diagnosis

  • Currently, no consensus diagnostic criteria for AIP has been established; however, several groups have outlined useful diagnostic criteria
  • 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 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
    • RF, anti SS-A, anti SS-B, AMA
    • 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)
  • ECRP/MRCP – may be necessary for equivocal cases

Differential Diagnosis

Autoimmune pancreatitis (AIP) is a rare 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 – >50 years
    • Type 2 – younger than type 1
  • Sex
    • Type 1 – M>F; 2-3:1
    • Type 2 – M:F, equal


  • Type 1 – pancreatic manifestation of multiorgan disease (bile duct, salivary gland, lymph nodes, kidneys, retroperitoneum) named immunoglobulin IgG4 related disease
  • Type 2 – pancreas specific disorder not associated with elevated IgG4
    • ​May be associated with ulcerative colitis


  • Type 1
    • Histologic hallmark is collar-like preductal infiltrates composed of lymphocytes and plasma cells termed lymphoplasmacytic sclerosing pancreatitis (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
    • May be focal or diffuse (duct centric)
      • Focal often resembles pancreatic mass (cancer)
    • Histologic hallmark is idiopathic, duct-centric pancreatitis

Clinical Presentation

  • Constitutional symptoms – weight loss, fatigue
    • Marked anorexia, cachexia suggest carcinoma
  • Pancreatic symptoms
    • Obstructive jaundice – often painless
    • Abdominal pain – not severe
      • Marked pain suggests carcinoma
    • Diabetes
  • Type 1 frequently coexists with another autoimmune disease (eg, chronic sclerosing sialoadenitis, primary sclerosing cholangitis, or primary biliary cirrhosis)
  • Extrapancreatic symptoms in type 1
    • Pulmonary – solid nodular, alveolar interstitial, ground glass opacities, bronchovascular
    • Renal – tubulointerstitial nephritis most common
    • Gastrointestinal – sclerosing cholangitis, retroperitoneal fibrosis
    • Salivary glands – chronic sclerosing sialadenitis
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.

Lipase, Serum or Plasma 0020014
Method: Quantitative Enzymatic

Immunoglobulin G Subclass 4 0050576
Method: Quantitative Nephelometry


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

Immunoglobulin G4 by Immunohistochemistry 2005844
Method: Immunohistochemistry


Chari ST, Smyrk TC, Levy MJ, Topazian MD, Takahashi N, Zhang L, Clain JE, Pearson RK, Petersen BT, Vege SS, Farnell MB. Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol. 2006 Aug;4(8):1010-6; quiz 934. Epub 2006 Jul 14. PubMed

Ikeura T, Manfredi R, Zamboni G, Negrelli R, Capelli P, Amodio A, Caliò A, Colletta G, Gabbrielli A, Benini L, Okazaki K, Vantini I, Frulloni L. Application of international consensus diagnostic criteria to an Italian series of autoimmune pancreatitis. United European Gastroenterol J. 2013; 1(4): 276-84. PubMed

Okazaki K, Kawa S, Kamisawa T, Ito T, Inui K, Irie H, Irisawa A, Kubo K, Notohara K, Hasebe O, Fujinaga Y, Ohara H, Tanaka S, Nishino T, Nishimori I, Nishiyama T, Suda K, Shiratori K, Shimosegawa T, Tanaka M. Japanese clinical guidelines for autoimmune pancreatitis. Pancreas. 2009 Nov;38(8):849-66. PubMed

Shimosegawa T, Chari ST, Frulloni L, Kamisawa T, Kawa S, Mino-Kenudson M, Kim MH, Klöppel G, Lerch MM, Löhr M, Notohara K, Okazaki K, Schneider A, Zhang L; International Association of Pancreatology. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011 Apr;40(3):352-8. PubMed

General References

Dite P, Novotny I, Trna J, Sevcikova A. Autoimmune pancreatitis. Best Pract Res Clin Gastroenterol. 2008; 22(1): 131-43. PubMed

Frulloni L, Amodio A, Katsotourchi AM, Vantini I. A practical approach to the diagnosis of autoimmune pancreatitis. World J Gastroenterol. 2011; 17(16): 2076-9. PubMed

Mihaljevic AL, Calzada-Wack J, Hölzlwimmer G, Tost M, Esposito I. Histopathological features of autoimmune pancreatitis. Minerva Gastroenterol Dietol. 2008; 54(4): 365-74. PubMed

Morselli-Labate AM, Pezzilli R. Usefulness of serum IgG4 in the diagnosis and follow up of autoimmune pancreatitis: A systematic literature review and meta-analysis. J Gastroenterol Hepatol. 2009; 24(1): 15-36. PubMed

O'Reilly DA, Malde DJ, Duncan T, Rao M, Filobbos R. Review of the diagnosis, classification and management of autoimmune pancreatitis. World J Gastrointest Pathophysiol. 2014; 5(2): 71-81. PubMed

Okazaki K, Tomiyama T, Mitsuyama T, Sumimoto K, Uchida K. Diagnosis and classification of autoimmune pancreatitis. Autoimmun Rev. 2014; 13(4-5): 451-8. PubMed

Sah RP, Chari ST. Autoimmune pancreatitis: an update on classification, diagnosis, natural history and management. Curr Gastroenterol Rep. 2012; 14(2): 95-105. PubMed

Sato Y, Notohara K, Kojima M, Takata K, Masaki Y, Yoshino T. IgG4-related disease: historical overview and pathology of hematological disorders. Pathol Int. 2010; 60(4): 247-58. PubMed

Stone JH, Brito-Zerón P, Bosch X, Ramos-Casals M. Diagnostic Approach to the Complexity of IgG4-Related Disease. Mayo Clin Proc. 2015; 90(7): 927-39. PubMed

Sugumar A, Chari ST. Autoimmune pancreatitis. J Gastroenterol Hepatol. 2011; 26(9): 1368-73. PubMed

Medical Reviewers

Last Update: July 2017