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