Guidelines for diagnosis & management of autoimmune pancreatitis

1. Autoimmune pancreatitis
International consensus diagnostic criteria
Samir Haffar M.D.
Assistant Professor of Gastroenterology
Al-Mouassat University Hospital – Damascus – Syria

2. History of autoimmune pancreatitis
Sarle 1961 Idiopathic chronic pancreatitis with elevated γG
Yoshida 1995 Propose concept of autoimmune pancreatitis
Hamano 1995 Increased serum levels of IgG4 in AIP
JPS 2002 Japan Pancreas Society: 1st guidelines of AIP
Kamisawa 2003 Novel entity: IgG4-related sclerosing disease
Chari 2010 Two distinct subtypes: type 1 & type 2
Honolulu consensus
Sarles H et al. Am J Dig Dis 1961 ; 6 : 688 – 698.
Yoshida K et al. Dig Dis Sci 1995 ; 40 : 1561 – 1568.
Hamano H et al. New Engl JMed 1995 ; 344 : 732 – 738.
Japan Pancreas Society. J Jpn Pancreas 2002 ; 17 : 585 – 7.
Kamisawa T et al. J Gastroenterol 2003 ; 203 ; 38 : 982 – 984.
Chari ST et al. Pancreas. 2010 ; 39 : 549 – 554.

3. Increased number of published papers on
autoimmune pancreatitis
Searching in Pubmed up to 2009
Search terms: autoimmune pancreatitis – Limit: field title
Frulloni L et al. World J Gastroenterol 2011 ; 17 : 2076 – 2079.

4. Definition of AIP
Distinct form of pancreatitis characterized by
• Clinic Frequently present with obstructive jaundice
With or without a pancreatic mass
• Histology Lympho-plasmacytic infiltrate & fibrosis
• Treatment Dramatic response to steroids
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

5. Pancreatic presentation of AIP
• Acute Pancreatic mass/obstructive jaundice
Acute pancreatitis
• Chronic Asymptomatic pancreatic mass
Burnt out stage Painless chronic pancreatitis
Steatorrhea with atrophic pancreas
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

6. How is autoimmune pancreatitis found?
• Gastroenterologist
Differential diagnosis of pancreatic or biliary cancers
Differential diagnosis of PSC
• Otolaryngologist, ophthalmologist, or rheumatologist
Sjögren syndrome
• Urologist
Examination for retroperitoneal fibrosis
Okazaki K et al. Pancreas 2009 ; 38 : 849 – 866.

7. When not to suspect AIP?
• Features of cancer Narcotic requiring pain
Marked anorexia/cachexia
Dialated PD/ pancreatic atrophy
• Recurrent pancreatitis without biliary involvement
• Dyspepsia with mild increased of pancreatic enzymes

8. Diagnosis of AIP
Combination of 1 or more of 5 cardinal features
HISORt
Histology
LPSP – IDCP
TCB/resection
Imaging
Parenchyma US – EUS – CT – PET – MRI
Pancreatic Duct ERCP – MRCP
Serology IgG4
Other Organ Involvement IgG4-related diseases – IBD
Response to therapy Steroid trial
LPSP: Lympho-Plasmacytic Sclerosing Pancreatitis
IDCP: Idiopathic Duct-Centric Pancreatitis
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

9. Diagnosis of AIP
Combination of 1 or more of 5 cardinal features
HISORt
Histology
LPSP – IDCP
TCB/resection
Imaging
Parenchyma US – EUS – CT – PET – MRI
Pancreatic Duct ERCP – MRCP
Serology IgG4
Other Organ Involvement IgG4-related diseases – IBD
Response to therapy Steroid trial
LPSP: Lympho-Plasmacytic Sclerosing Pancreatitis
IDCP: Idiopathic Duct-Centric Pancreatitis
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

10. Comparison of type 1 & type 2 AIP
Type 1 Type 2
AIP without GELs AIP with GELs
Age Elderly Young
Gender Predominantly male Equal
Distribution Whole word Western countries
Serum IgG4 Elevated Normal
Histopathology LPSP IDCP
Infiltrating cells IgG4 + plasma cells Granulocytes
Relapse rate High Low
Extra-pancreatic lesions IgG4-related disease IBD (30%)
GEL: Granulocyte Epithelial Lesions
LPSP: Lympho-Plasmacytic Sclerosing Pancreatitis
IDCP: Idiopathic Duct-Centric Pancreatitis
Chari ST et al. Pancreas 2010 ; 39 : 549 – 554.

11. IgG4-related sclerosing disease
Kamisawa T et al. Expert Opin Pharmacother 2011 ; 12 : 2149 – 2159.

12. Lympho-plasmacytic sclerosing pancreatitis (LPSP)
AIP without GEL*
Systemic disease: IgG4-related disease
• Periductal lympho-plasmacytic infiltrate
• Peculiar storiform fibrosis
• Obliterative Venulitis: by lymphocytes & plasma cells
• Abundant IgG4 positive plasma cells: > 10 cells/hpf
Definite diagnosis can be made without histology
* GEL: Granulocyte Epithelial Lesions
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

13. Histopathological findings of AIP / LPSP
H&E staining IgG4 immuno-staining
Infiltration of plasma cells & lymphocytes Abundant infiltration of
‘storiform fibrosis’’ IgG4-positive plasma cells
Shimosegawa T & Kanno A. J Gastroenterol. 2009 ; 44 : 503 – 17.

14. Obliterative venulitis
H&E stain Movat pentachrome stain
Lymphoplasmacytic infiltration
Artery easily found
Fibrosis destroying vein wall
Poorly visualizes obliterative venulitis
resulting in narrowing & occlusion
Law R et al. Clev Clin J Med 2009 ; 76 : 607 – 615.

15. Idiopathic Duct-Centric Pancreatitis (IDCP)
AIP with GEL*
Pancreas-specific disorder
• Periductal lympho-plasmacytic infiltrate
• Peculiar storiform fibrosis
• None or very few IgG4-positive plasma cells: < 10 cells/hpf
• GEL Intra-luminal & intra-epithelial neutrophils
Medium-sized & small ducts as well as acini
Destruction & obliteration of duct lumen
Definite diagnosis requires histological examination
* GEL: Granulocyte Epithelial Lesions
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

16. Idiopathic Duct-Centric Pancreatitis (IDCP)
H&E staining H&E staining
Periductal inflammation Inflammatory cells few in fibrosis
Destruction of pancreatic epithelia Microabscess in intra-lobular duct
Suggested GEL
GEL: Granulocyte Epithelial Lesions
Kusuda T et al. Intern Med 2010 ; 49 : 2569 – 2575.

17. What to biopsy?
Histopathology is diagnostic but not usually available
• Pancreatic biopsy EUS-FNA: not reliable
EUS-TCB: better sen & sp
Surgery
• Papillary biopsy Specific, not very sensitive
• Intraductal BD biopsy Still under debate
• Liver biopsy Not strictly necessary
Maillette de BuyWenniger L et al. Endoscopy 2012 ; 44 : 66 – 73.

18. Diagnosis of AIP
Combination of 1 or more of 5 cardinal features
HISORt
Histology
LPSP – IDCP
TCB/resection
Imaging
Parenchyma US – EUS – CT – PET – MRI
Pancreatic Duct ERCP – MRCP
Serology IgG4
Other Organ Involvement IgG4-related diseases – IBD
Response to therapy Steroid trial
LPSP: Lympho-Plasmacytic Sclerosing Pancreatitis
IDCP: Idiopathic Duct-Centric Pancreatitis
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

19. Ultrasonograpy in AIP
Trans-abdominal transverse US
Diffuse enlargement of pancreas
Minimal decreased echotexture
“sausage-like appearance”
Sahani DV et al. Radiology 2004 ; 233 : 345 – 352.

20. EUS findings in autoimmune pancreatitis
• Diffuse form Diffuse pancreatic enlargement
Chronic pancreatitis Reduced echogenicity
Hyperechoic foci & strands
• Focal form Solitary irregular hypoechoic mass
Pancreatic cancer Upstream dilatation of MPD
Vascular invasion of PV & MV
Real-time tissue elastography
Buscarini E et al. World J Gastroenterol 2011 ; 17 : 2080 – 2085.

21. Diffuse form of autoimmune pancreatitis
EUS
Diffuse pancreatic enlargement Parenchymal lobularity
Echopoor echotexture Hyperechoic strands
Loss of interface with splenic vein
Buscarini E et al. World J Gastroenterol 2011 ; 17 : 2080 – 2085.

22. Focal form of autoimmune pancreatitis
EUS Interventional EUS
Focal lesion of pancreatic head FNA: Sen 36% – Sp 33%
Echopoor with hyperechoic strands TCB: Sen 100% – Sp 100%
FNA first then TCB
FNA: Fine Needle Aspiration – TCB: Tru-Cut Biopsy
Mizuno N et al. J Gastroenterol 2009 ; 44 : 742 – 750.
Buscarini E et al. World J Gastroenterol 2011 ; 17 : 2080 – 2085.

23. Focal form of AIP
Real-time tissue elastography
5 AIP – 17 ductal adenocarcinoma – 10 healthy subjects
Stiff pattern of pancreatic mass & surrounding parenchyma
Distinguishes AIP from ductal adenocarcinoma
Dietrich CF et al. Endoscopy 2009 ; 41 : 718 – 720.

24. Localized form of AIP
Localized hypoechoic mass
Hyperechoic inclusions “duct-penetrating sign”
“tortoiseshell pattern”
Okazaki K et al. Pancreas 2009 ; 38 : 849 – 866.

25. Enlarged lymph nodes in hepatic hilum
Buscarini E et al. World J Gastroenterol 2011 ; 17 : 2080 – 2085.

26. EUS nodal features predicting metastasis
• Size: > 1 cm in diameter on short axis
• Hypoechoic appearance
• Round shape
• Smooth border
Identified in esophageal cancer 1
Inaccurate for other cancers including biliopancreatic 2
1 Catalano MF et al. Gastrointest Endosc 1994 ; 40 : 442 – 446.
2 Gleeson FC et al. Gastrointest Endosc 2008 ; 67 : 438 – 443.

27. CT scan in auto-immune pancreatitis
• Diffusely or locally enlarged pancreas
• Distinctive delayed enhancement pattern with various
images depending on activity or stages of disease
• Capsule-like rim: highly specific
Okazaki K et al. Pancreas 2009 ; 38 : 849 – 866.

28. Dynamic CT of AIP
Early imaging Delayed imaging
Swollen pancreas Delayed gradual enhancement
Low density „„capsule-like rim‟‟
Shimosegawa T & Kanno A. J Gastroenterol. 2009 ; 44 : 503 – 17.

29. Dynamic CT in auto-immune pancreatitis
Diffusely enlarged pancreas
Slow and delayed enhancement
Capsule-like rim
Okazaki K et al. Pancreas 2009 ; 38 : 849 – 866.

30. Positron emission tomography in AIP
• Accumulation of FDG in pancreatic & extra-pancreatic
lesions, which disappear shortly after steroid treatment
• Characteristic accumulation pattern & kinetics in
pancreatic & extra-pancreatic lesions after steroid
treatment can be used for diagnosis of disease
FDG: Fluoro Deoxy Glucose
Okazaki K et al. Pancreas 2009 ; 38 : 849 – 866.

31. Whole-body FDG-PET imaging in AIP
Before steroid After steroid
FDG taken to pancreatic body & tail,
FDG disappears shortly after
salivary glands, pulmonary hilar LN
starting steroid treatment
& large pseudotumor of liver
Okazaki K et al. Pancreas 2009 ; 38 : 849 – 866.

32. PET/CT scan image
65-year-old man with autoimmune pancreatitis
Diffuse pancreatic involvement
Increased 18 F-FDG uptake in enlarged pancreas
Bodily KD et al. Am J Roentol 2009 ; 192 : 431 – 437.

33. Magnetic resonance images of AIP
• Diffusely enlarged pancreas with
Low signal on T1-weighted images
Delayed enhancement pattern on dynamic MRI
• Capsule-like rim
Strong fibrosis of peripancreatic lesion: highly specific
Okazaki K et al. Pancreas 2009 ; 38 : 849 – 866.

34. MR imaging of AIP
T2-weighted MRI Gd-enhanced MRI
Swollen pancreas (low signal) „„Capsule-like rim‟‟
„„Capsule-like rim‟‟ (low signal) Depicted more clearly
Shimosegawa T & Kanno A. J Gastroenterol. 2009 ; 44 : 503 – 17.

35. ERCP criteria to diagnose AIP
International multicentre study
• 21 physicians from four centers in Asia, Europe & USA
40 ERPs: 20 AIP, 10 chronic pancreatitis, 10 pancreatic cancer
• Phase I → Washout period (3 months) → Phase II
• Key features Long stricture: > 1/3 length of PD
Lack of upstream dilatation: < 5 mm
Multiple strictures
Side branches arising from strictured segment
• Results Sen 71% – Sp 83% – IOA 0.40
Sugumar A et al. Gut 2011 ; 60 : 666 – 670.

36. ERCP criteria to diagnose AIP
International multicentre study
Ability to diagnose AIP based on ERP features alone is limited
Diagnosis improved with knowledge of some key features
Sugumar A et al. Gut 2011 ; 60 : 666 – 670.

37. MRCP in auto-immune pancreatitis
Narrowing of main pancreatic duct (tail)
MRCP not recommended for accurate evaluation of MPD narrowing
Okazaki K et al. Pancreas 2009 ; 38 : 849 – 866.

38. Diagnosis of AIP
Combination of 1 or more of 5 cardinal features
HISORt
Histology
LPSP – IDCP
TCB/resection
Imaging
Parenchyma US – EUS – CT – PET – MRI
Pancreatic Duct ERCP – MRCP
Serology IgG4
Other Organ Involvement IgG4-related diseases – IBD
Response to therapy Steroid trial
LPSP: Lympho-Plasmacytic Sclerosing Pancreatitis
IDCP: Idiopathic Duct-Centric Pancreatitis
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

39. Serum IgG4 & autoimmune pancreatitis
• Normal value 8 – 140 mg/dl
• Initial reports Pathognomonic
• Subsequent reports Characteristic not diagnostic
• Sen & Sp 75% – 93%
• PPV Low (not used alone for dg)
• Level > 2 times ULN is highly specific
Park DH et al. Gut 2009 ; 58 : 1680 – 1689.

40. Serum IgG4 in diagnosing AIP
510 patients
Cutoff > 140 mg/dL: Sen 76% – Sp 93% – PPV 36%
Cutoff > 280 mg/dL: Sen 53% – Sp 99% – PPV 75%
Ghazale A et al. Am J Gastroenterol 2007 ; 102 : 1646 – 1653.

41. Diagnosis of AIP
Combination of 1 or more of 5 cardinal features
HISORt
Histology
LPSP – IDCP
TCB/resection
Imaging
Parenchyma US – EUS – CT – PET – MRI
Pancreatic Duct ERCP – MRCP
Serology IgG4
Other Organ Involvement IgG4-related diseases – IBD
Response to therapy Steroid trial
LPSP: Lympho-Plasmacytic Sclerosing Pancreatitis
IDCP: Idiopathic Duct-Centric Pancreatitis
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

42. Predominantly extra-pancreatic presentation
• Biliary stricture
Resembling: PSC – Pancreatic cancer – Cholangiocarcinoma
• Interstitial nephritis
• Retroperitoneal fibrosis
• Diffuse lymphoanenopathy
• Sjögren‟s syndrome

43. Diagnosis of other organ involvement
• Clinical examination Symmetrical salivary gland enlargement
• Imaging Proximal bile duct stricture
Retroperitoneal fibrosis
Renal or pulmonary lesion
• Histology Lymphoplasmacytic infiltrate
> 10 IgG4 + plasma cells/hpf
Storiform fibrosis
Obliterative phlebitis
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

44. Thickening of bile duct wall in AIP
Three-layer type Parenchymal echo type
Koyama R et al. Pancreas 2008 ; 37 : 259 – 264.

45. Biliary & peripancreatic findings in AIP
Dilated CBD upstream to distal funnel-shaped stenosis
Diffuse thickening of biliary wall
Enlarged lymph nodes in hepatic hilum
Buscarini E et al. World J Gastroenterol 2011 ; 17 : 2080 – 2085.

46. Bile duct wall thickening
“sandwich-pattern”
Intermediate echo-poor layer & echo-rich inner & outer layers
Buscarini E et al. Dig Liver Dis 2010 ; 42 : 92 – 98.

47. Thickening of IHBD
Trans-abdominal US
Parenchymal-echo type thickening
Koyama R et al. Pancreas 2008 ; 37 : 259 – 264.

48. Thickening of bile duct wall
• Acute cholangitis More or less symmetric
• Primary sclerosing cholangitis Asymmetric
• Secondary sclerosing cholangitis Symmetric
European Foundation of Societies of Ultrasound in Medicine & Biology.
Barreiros AP et al. European Course Book – Ultrasound of the biliary sydtem – 2011.

49. Thickening of bile duct wall/Acute cholangitis
More or less symmetrical thickening of bile duct walls
European Foundation of Societies of Ultrasound in Medicine & Biology.
Barreiros AP et al. European Course Book – Ultrasound of the biliary sydtem – 2011.

50. Thickening of bile duct wall/PSC
Asymmetric thickening of bile duct walls
Benign strictures & alternating dilatations
European Foundation of Societies of Ultrasound in Medicine & Biology.
Barreiros AP et al. European Course Book – Ultrasound of the biliary sydtem – 2011.

51. Secondary causes of sclerosing cholangitis
Distinguishing PSC from SSC may be challenging
Choledocholithiasis
Recurrent pyogenic cholangitis
Cholangiocarcinoma
AIDS cholangiopathy
Diffuse intrahepatic metastasis
Eosinophilic cholangitis
Hepatic inflammatory pseudo-tumor
Histocytosis X
IgG4-associated cholangitis
Intra-arterial chemotherapy
Ischemic cholangitis
Portal hypertensive biliopathy
Recurrent pancreatitis
Surgical biliary trauma
Chapman R et al. Hepatology 2010 ; 51 : 660 – 678.

52. AIP with common bile duct involvement
Stenosis of the distal CBD
ERCP hallmark of AIP
Buscarini E et al. Dig Liver Dis 2010 ; 42 : 92 – 98.

53. Cholangiography in PSC & AIP
PSC AIP
Kawa S et al. J Gastroenterol 2010 ; 45 : 355 – 369.

54. Does ERC distinguish IgG4-associated cholangitis
from PSC or cholangiocarcinoma?
• 17 physicians from USA, Japan, & UK
• Unaware of clinical data
• 40 ERCs IgG4-associated cholangitis: 20 patients
PSC: 10 patients
Cholangiocarcinoma: 10 patients
• Results Sensitivity: 45%
Specificity: 88%
Inter-observer agreement: 0.18
IAC may be misdiagnosed with PSC or cholangiocarcinoma
Kalaitzakis E et al. Clinical Gastroenterol Hepatol 2011 ; 9 : 800 – 803.

55. ERC in IgG4-associated cholangitis & PSC
IgG4-associated cholangitis PSC
Difficulty to distinguish IAC from PSC based on ERC
de BuyWenniger LM et al. Endoscopy 2012 ; 44 : 66 – 73.

56. In all patients with possible PSC,
we suggest measuring serum IgG4 levels
to exclude IgG4-associated sclerosing cholangitis
AASLD practice guidelines: Diagnosis & management of PSC.
Chapman R et al. Hepatology 2010 ; 51 : 660 – 678.

57. HISORt criteria for diagnosis of AIP-SC
H Lymphoplasmacytic sclerosing cholangitis on resection:
Bile duct LP infiltrate, > 10 IgG4 + cells/hpf, storiform fibrosis, phlebitis
I One or more strictures involving IH, EH, or intrapancreatic BD
Bile duct Fleeting/migrating biliary strictures
S IgG4 > 2 ULN value
O Pancreas: Classic features of AIP on imaging or histology
Suggestive imaging findings: mass, stricture, atrophy
Retroperitoneal fibrosis
Renal: single/multiple parenchymal low-attenuation lesions
Salivary/lacrimal gland enlargement
Rt Normalization of liver enzyme or resolution of BD stricture
Definitive dg Group A: diagnostic histology on resection or TCB
Group B: typical imaging of AIP + serology
Probable dg Group C: ≥ 2 of suggestive pancreatic imaging, S, OOI & Rt
Ghazale A et al. Gastroenterology 2008 ;134 :706 – 715.

58. IgG4-associated cholecystitis
Another clue in diagnosis of autoimmune pancreatitis
Leise MD et al. Dig Dis Sci 2011 ; 56 : 1290 – 1294.

59. Duodenal papilla in AIP
IgG4 immuno-staining of papilla in 19 AIP & 100 controls
Sensitivity 53% – 100 % specificity
Endoscopic view of papilla IgG4 immuno-staining
Swollen duodenal papilla 50 IgG4-positive cells/HPF
Kubota K et al. Gastrointest Endosc 2008 ; 68 : 1204 – 1208.
Moon SH et al. Gastrointest Endosc 2010 ; 71 : 960 – 966.

60. AIP with idiopathic retroperitoneal fibrosis
CECT scan CECT scan slightly inferior
Diffusely enlarged pancreas Bilateral peri-pelvic lesions
Low-density rim Left peri-renal lesions
Fukukura Y et al. Am J Roentgenol 2003 ; 181: 993 – 995.

61. Retroperitoneal fibrosis
Transverse CT scan at level of origin of IMA
Circumferential thickening of aortic wall
with peri-aortic soft tissue
Sahani DV et al. Radiology 2004 ; 233 : 345 – 352.

62. AIP with renal involvement
Contrast-enhanced axial CT
Multiple well-defined round lesions in both kidneys
Bodily KD et al. AJR 2009 ; 192 : 431 – 437.

63. Diagnosis of AIP
Combination of 1 or more of 5 cardinal features
HISORt
Histology
LPSP – IDCP
TCB/resection
Imaging
Parenchyma US – EUS – CT – PET – MRI
Pancreatic Duct ERCP – MRCP
Serology IgG4
Other Organ Involvement IgG4-related diseases – IBD
Response to therapy Steroid trial
LPSP: Lympho-Plasmacytic Sclerosing Pancreatitis
IDCP: Idiopathic Duct-Centric Pancreatitis
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

64. Steroid trial in AIP
Mass in pancreatic body Long narrowing of MPD
0.6 – 1 mg/kg of oral prednisolone/day for 2 weeks
Mass markedly reduced Almost normal MPD
2-week steroid trial may be helpful to confirm diagnosis of AIP
Moon SH et al. Gut 2008 ; 57 : 1704 – 1712.

65. IgG4-associated sclerosing cholangitis
Before treatment After 12 weeks of steroid therapy
IH strictures mimicking PSC Resolution of IH strictures
Ghazale A et al. Gastroenterology 2008 ;134 :706 – 715.

66. Inflammatory pseudo-tumor
Before steroid therapy After steroid therapy
Nodular lesion of inflammatory
Nodular lesion disappeared
pseudo-tumor
Kawa S et al. J Gastroenterol 2010 ; 45 : 355 – 369.

67. Caution regarding steroid trial
• Not to be used as substitute for thorough search
for etiology
• Do not use it if there is no objective way to define
response

68. Challenges to diagnosing AIP
• Closely mimics other well known diseases
Pancreatic cancer & PSC: need high index of suspicion
• Rare compared to diseases it mimics
2 – 3 % of patients suspected to have pancreatic cancer
• No single test is diagnostic
Histology is diagnostic but rarely available
• Heavy price of misdiagnosis
AIP mistaken for cancer results in major surgery
Cancer mistaken for AIP results in delay in surgery

69. Diagnostic criteria for AIP
Lack of universally accepted criteria
Dg criteria References
Japan Japan Pancreas Society. J Jpn Pancreas 2002;17:585-7.
Okazaki K et al. J Gastroenterol 2006;41 626-31.
Okazaki K et al. Pancreas 2009;38: 849-866.
Pearson RK et al. Pancreas 2003;27:1-13.
Italy
Frulloni L et al. Am J Gastroenterol 2009;104:2288-94.
Korea Kim KP et al. World J Gastroenterol 2006;12:2487-96.
US (Mayo Clinic) Chari ST et al. Clin Gastroenterol Hepatol 2006;4:1010-6.
HISORt Chari ST et al. Clin Gastroenterol Hepatol 2009;7:1097-2003.
Asia Otsuki M et al. J Gastroenterol 2008;43:403-408.
Germany Schneider A & Löhr JM. Internist (Berlin) 2009;50:318-330.

70. Why an international consensus on AIP?
• ERP Routinely used in Japan (mandatory criterion)
AIP diagnosed without ERP in the West
• Biopsy Core biopsy for diagnosis by Mayo Clinic group
Not routinely used elsewhere
• 2 types Asian & American criteria diagnose type 1
Italian criteria have mixture of types 1 & 2
Criteria applied worldwide
Safely diagnose AIP
Avoid misdiagnosis of AIP as pancreatic cancer or PSC
Chari ST et al. Pancreas. 2010 ; 39 : 549 – 554.
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

71. Honolulu consensus conference on AIP 1
AIP International Cooperative Study Group
Honolulu, Hawaii: November 4, 2009
33 international experts – Categorization into type 1 & type 2
International consensus diagnostic criteria for AIP 2
14th congress of International Association of Pancreatology
Fukuoka, Japan: July 11 – 13, 2010
14 international experts – Consensus opinion of working group
1 ChariST et al. Pancreas. 2010 ; 39 : 549 – 554.
2 Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

72. Level 1 & level 2 criteria for type 1 AIP
Criterion Level 1 Level 2
Histology of pancreas LPSP (TCB or resection) LPSP (TCB)
At least 3 of 4 At least 2 of 4
Parenchyma imaging Typical Indeterminate/atypical*
Diffuse enlargement Segmental/focal enlargement
Delayed enhancement rim Delayed enhancement
Ductal imaging Long stricture (>1/3 MPD) Segmental/focal narrowing
(ERP) or multiple strictures without dilatation (< 5 mm)
without dilatation (< 5mm)
Serology IgG4: > 2 ULN IgG4: 1 – 2 ULN
OOI a: histology (3 of 4) a: histology (LP & >10 /hpf)
a or b b: radiology (bile duct, RPF) b: clinic (salivary, lachrymal)
radiology (renal lesion)
Response to therapy Rapid (≤ 2 wk) radiological resolution/marked improvement
LPSP: Lympho-Plasmacytic Sclerosing Pancreatitis
* Atypical parenchymal imaging: low-density mass, ductal dilatation, distal atrophy
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

73. Diagnosis of definitive & probable type 1 AIP
Diagnosis Basis for dg Imaging evidence Collateral evidence
Histology Typical/indeterminate LPSP (level 1 H)
Imaging Typical/indeterminate Any non-D level 1/ level 2
Definitive ≥ 2 from level 1(+level 2 D)
Response to steroid Indeterminate Level 1 S/O or
Level 1 D + level 2 S/O/H
Probable Indeterminate Level 2 S/O/H + Rt
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

74. Level 1 & level 2 criteria for type 2 AIP
Criterion Level 1 Level 2
Histology of pancreas ICDP: both of the following Both of the following:
(TCB or resection) 1- GEL G acinar inflamation 1- LP & G acinar infiltrate
2- Scanty to no IgG4 + cells 2- Scanty to no IgG4 + cells
Parenchyma imaging Typical Indeterminate/atypical*
Diffuse enlargement Segmental/focal enlargement
Delayed enhancement rim Delayed enhancement
Ductal imaging Long stricture (>1/3 of MPD) Segmental/focal narrowing
(ERP) or multiple strictures without dilatation (< 5 mm)
without dilatation (< 5mm)
OOI – Clinically diagnosed IBD
Response to therapy Rapid (≤ 2 wk) radiological resolution/marked improvement
after negative workup for cancer including EUS-FNA
GEL: Granulocyte Epithelial Lesions
IDCP: Idiopathic Duct-Centric Pancreatitis
Atypical parenchymal imaging: low-density mass, ductal dilatation, distal atrophy
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

75. Diagnosis of definitive & probable type 2 AIP
Diagnosis Imaging evidence Collateral evidence
Definitive Typical/indeterminate Histologically confirmed IDCP (level 1 H)
or clinical IBD + level 2 H + Rt
Probable Typical/indeterminate Level 2 H / clinical IBD + Rt
Shimosegawa T et al. Pancreas 2011 ; 40 : 352 – 358.

76. References

77. Thank You