Autoimmune Pancreatitis - a diagnostic challenge Dr. Lee Ka Yan Tuen Mun Hospital
Feb 12, 2016
Autoimmune Pancreatitis- a diagnostic challenge
Dr. Lee Ka YanTuen Mun Hospital
Autoimmune Pancreatitis
• Introduction
• A case with autoimmune pancreatitis
• Diagnostic features and criteria
• Differentiation from Pancreatic Cancer
• Summary
Autoimmune Pancreatitis (AIP)• A special type of chronic pancreatitis with distinct
features• pathological• radiological • Immunological
• Extremely difficult to distinguish from malignancy• Obstructive jaundice• Weight loss• Mass in head of pancreas
• Prompts a number of major resections (up to 20% in one Japanese Study)
• Response to steroid treatment, some with complete disease remission
Epidemiology
• Prevalence 4-6% of chronic pancreatitis (as high as 11%, Pearson et al. Pancreas 2003)
• Male predominance• Age > 45 (youngest 10 years old)
• Absence of gallstone or excess alcohol consumption
A case with Autoimmune Pancreatitis
Mr. Lee• M/68
• Presented with obstructive jaundice• Deranged LFT
• TB 80 ALP 352 ALT 355
• USG abdomen • CBD 9mm and prominent IHDs
• ERCP• lower CBD stricture and proximal
dilatation, plastic stent inserted
• MRCP• intrahepatic duct dilatations
• Contrast CT abdomen• Biliary tract obstruction with stent in
common duct
• EUS Pancreas• mildly dilated CBD down to lower end• bulky pancreatic head but no obvious
lesion seen • a 7mm retropancreatic LN
• Ca19.9 – 5.6
Exploratory Laparotomy + Whipple Operation
• PANCREATITIS• Increased IgG4 plasma cell infiltration,
suggestive of autoimmune pancreatitis
• IgG4 600 (0-291)
• ANCA, ANA positive
Pathology
Autoimmune Pancreatitis
Clinical Features• Mild abdominal pain• Obstructive jaundice – 70-80% • Anorexia and weight loss
• Diabetes Mellitus -- up to 76%
Extra-Pancreatic involvement
Chronic sclerosing sialadenitis
Retroperitoneal fibrosis
IgG4-associated Tubulointerstitial
nephritisIgG4-
associated cholangitis
Interstitial pneumonia
Inflammatory aortic
aneurysm
Diagnostic Criteria
• Japan Pancreas Society (JPS) Criteria• 2002 and revised 2006
• Kim Criteria (Korea)
• HISORt Critera (Mayo Clinic)
Kim Criteria (Korea)
Radiological Features – CT
Autoimmune Pancreatitis
Pancreatic Cancer
Diffuse enlargement of pancreas Parenchymal atrophy above stricture
Delayed enhancement of pancreatic mass
Poor enhancement
Diffuse narrowing main pancreatic duct
Single localized stricture
Minimal upstream duct dilatation Marked upstream duct dilatation
Other organs involvement (kidney, retroperitoneal fibrosis)
No other organ involvement
Radiological Features – ERCP/MRCP
- Diffuse or segmental narrowing of main pancreatic duct
Radiological Features – PET-CT
• Intense uptake
• Disappear after steroid treatment
Kim Criteria (Korea)
Laboratory Features
• Serum IgG4 -- raised in up to 94% (Hirano et al.) • >135mg/dl (Hamano et al.)
• Accuracy 97%• Sensitivity 95%• Specificity 97%
• Autoimmune antibodies
Kim Criteria (Korea)
EUS guided biopsy
• Sensitivity and accuracy >80%
• Lymphoplasmatic infiltrate• Immunostaining – IgG4 positive plasma
cells• Absence of malignant cells
• Avoid unnecessary surgery
Kim Criteria (Korea)
Response to Steroid Therapy
• Moon et al. Gut 2008• 22 patients with clinically suspected AIP
• 2 weeks course of steroid therapy (prednisolone 0.5mg/kg/day)
• FU CT and ERCP/MRCP
• Positive steroid response• Complete resolution or marked improvement
of main pancreatic ductal narrowing +/- reduction in size of pancreatic mass
Response to Steroid Therapy
• Positive steroid response : 15 / 22 patients• gradual taper and stopped• No malignancy
• Negative steroid response : 7 / 22 patients• Pancreatic surgery (except one refused)• All 6 patients -- pancreatic head cancer• Complete resection possible without
operation-related morbidity or mortality
Diagnostic algorithm
Clinical young, minimal weight loss,
mild abdominal pain
RadiologicalLack features of
pancreatic cancer
Extrapancreatic lesions
SerologyIgG4, autoantibodies
Pancreatic biopsyIgG4 Lymphoplasmacytic infiltration
No malignancy cells
Steroid
Responsiveness+ -Continue
Steroid Resection
Summary
• Autoimmune Pancreatitis is a challenging diagnosis to make and is difficult to differentiate from Pancreatic cancer
• Investigate more for possibility of Autoimmune Pancreatitis if features compatible
• Proceed to exploratory laparotomy +/- resection if cannot exclude malignancy
THE END
Diagnostic algorithm
Clinical young, minimal weight loss,
mild abdominal pain
RadiologicalLack features of
pancreatic cancer
Extrapancreatic lesions
SerologyIgG4, autoantibodies
Pancreatic biopsyIgG4 Lymphoplasmacytic infiltration
No malignancy cells
Steroid
Responsiveness+ -Continue
Steroid Resection
JPS Kim HISORt Italian
Imaging * Essential * Essential Not essential Not included
Laboratory Elevated IgG4
Elevated IgG4/IgG or autoantibodies
Elevated IgG4
Not included
Histopathology Marked lympho-plasmacytic infiltration and fibrosis
Lympho-Plasmacytic infiltration and fibrosis
*LPSPIgG4 plasma cells
* Histology or cytology
Response to Steroid
Not included Included Included Included
Other organ involvement
Not included Not included Included Included
HISORt Criteria
Japanese Criteria
Italian Criteria
Results of Surgery
• Hardacre et al. Annuals of Surgery 2003• Surgery for AIP associated with
difficulty in dissecting pancreas from SMV/portal vein
• Significant blood loss operating time
• No difference in LOS and overall complication rate
• 68% reported improved quality of life
• 37% developed DM ; 35% diarrhoea
Radiological Features – USG/EUS
• Hypoechoic• No calcification or cysts
Laboratory Features• Serum IgG4 -- raised in up to 94%
(Hirano et al.) • >135mg/dl (Hamano et al.)
• Accuracy 97%• Sensitivity 95%• Specificity 97%
• >280mg/dl (Ghazale et al.)
• AIP 53% • Pancreatic cancer patient 1%
• Autoimmune antibodies
Treatment
• Steroid• Oral prednisolone 30-40mg/day for 3-4
weeks tapering of various duration +/- maintainence therapy
• No consensus of dosage and duration
• Immunomodulatory medications• Azathioprine• Mycophenolate mofetil
Pathogenesis• Unclear• Autoimmune
• Elevated IgG4 level with lymphoplasmacytic infiltrates involving IgG4-positive plasma cells in affected organs
• Autoantibodies against carbonic anhydrase, lactoferrin and other antigens
• T helper Type 2 (Th2) cells and T regulatory (Tregs) cells predominate the immune reaction
• Strong association with other autoimmune conditions e.g Sjogren’s syndrome, PSC, IBD, SLE, retroperitoneal fibrosis, Hashimoto’s thyroiditis, etc
• Dramatic response to steroid
Gross Pathology
Histopathology• Lymhoplasmacytic sclerosing pancreatitis (LPSP)• Infiltration of IgG4-positive plasma cells (>10/HPF)
Periductal lymphoplasma infiltration with a storiform pattern
fibrosis
Obliterative phlebitis
EUS-guided Trucut Biopsy• Levy et al, Gastrointestinal Endoscopy 2005
• 3 patients with suspected AIP
• Results:• 2 patients -- AIP• 1 patient -- non-specific changes of
chronic pancreatitis
• Managed conservatively with close monitoring
• Avoidance of surgery
EUS-guided Trucut Biopsy
• Advantages• Larger biopsy specimen• EUS with superior resolution that can
improve accuracy of lesion targeting• Risk of seeding is lower than
transabdominal biopsy
• Drawbacks• Technically difficult (especially when
lesion at pancreatic head) due to angulation
• Patchy distributions of AIP may lead to false negative
Infiltration of IgG4-positive plasma cells
• Kamisawa et al. Gastrointestinal Endoscopy 2008 • Biopsy of major duodenal papilla • 10 AIP, 10 pancreatic cancer and 10
papillitis patients
• Immunostaining using anti-IgG4 antibodies• IgG4-positive plasma cells per high-power
field (HPF)
IgG4 plasma cells
Significant10/HPF
Moderate 4-9/HPF
Rare3/HPF
Autoimmune Pancreatitis
8 2(body/tail)
Pancreatic Cancer
0 1 9
Papillitis 0 0 10
Detection Rate Core Biopsy Resection
Bang et al. Pancreas 2008
26% 100%
Zamboni et al. Virchows Arch. 2004
22% 90%
Chari et al. Clin Gastroenterol Hepatol 2006
44% 92%
Sensitivity under influence of specimen size