RECAP: Autoimmune Pancreatitis - PowerPoint Presentation

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RECAP: Autoimmune Pancreatitis

Type 2: Idiopathic duct-centric pancreatitis

GELs: granulocite, ephitelial lesions

IgG-4 Related Diseases

Various

organ

manifestations of a fibro-inflammatory

condition

c

haracterized by

tumefactive lesions

recognised as a

systemic condition

in 2003

Linked by the

same histopathological characteristics

and

elevated serum IgG4

concentrations.

Multiple immune-mediated

mechanism contribute to the fibro-inflammatory process, being autoimmunity and infectious agents potential triggers of a Th-2 and T-reg response.

Pathophysiology

Stone J, Zen Y. IgG4-Related Disease N Engl J Med 2012;366:539-51.

IgG-4 Related Diseases

IgG-4 Related Pancreato-biliary Diseases

Majority of patients are men (60-73%), > 60 years

Prevalence 0,2-0,8/100.000

Lack of familiarity!

Up to 40% of patients have

allergic diseases

(atopy, eczema, asthma, chronic sinusitis)

30%

normal

serum IgG-4 concentrations

IgG-4 related

sclerosing cholangitis

associated with AIP in 47–92% of pt

IgG-4 Pancreatitis

Clinical presentation Acute vs Chronic symptoms Painless obstructive jaundice 33–60% Steatorrhea - exocrine functional abnormalities in up to 80% Abdominal pain 32% Back pain and weight loss 15% Serologic marker:  titers of g-globulin (>2000 mg/dL)  IgG (>1800 mg/dL)  IgG4 (>140 mg/dL)

Serum IgG4 >140 mg/dL

86% SN, 96% SP

IgG-4 Pancreatitis

Imaging features Enlarged pancreas “sausage-like appareance” 50-70% Focal masses 30% Soft tissue hypoenhancing rim Narrowing of main pancreatic duct “Duct-penetrating” sign at secretin-MRCP

IgG4 Pancreatitis: DD

IgG-4 Pancreatitis

Role of EUS-FNA Histological proof of the disease: GOLD STANDARD Exclusion of carcinoma Discrimination of type 1 from type 2 AIP

IgG4-positive plasma cells> 10/hpf

Diffuse lymphoplasmacytic

infiltration and storiform fibrosis

IgG-4 Pancreatitis

Hystology is the GOLD STANDARD:

Diffuse

lymphoplasmacytic

infiltration with mild-moderate

eosinophilia

Obliterative flebitis

and

storiform fibrosis

IgG4 immunostaining:

> 50 IgG4 plasma cells/HPF for surgical specimens

> 10 IgG4 plasma cells/HPF for biopsy samples

Ratio

IgG4

-positive/

IgG

-positive plasma cells > 40%

Storiform Fibrosis

IgG-4 Pancreatitis: diagnosis

The MAYO Clinic HISORt criteria

IgG-4 Cholangitis

Clinical presentation

70%

obstructive jaundice with pruritus and abdominal pain

Asymptomatic

jaundice less common than AIP

7-10%

cirrhosis

manifestation (hepatic failure, ascites, hepatic encephalopathy or variceal bleeding)

Serologic marker:



titers of g-globulin (>2000 mg/dL)



IgG (>1800 mg/dL)



IgG4 (>140 mg/dL)



reumatoid factor, antinucleus antibody

IgG-4 Cholangitis

Imaging features Isolated intrapancreatic CBD strictures Localized hilar hepatic lesion (strictures or masses) Intense and diffuse extension of bile duct wall homogeneous thickening (often circular) IDUS: inflamed submucosa and preserved epithelium, circular symmetric wall thickening

IgG-4 Cholangitis DD

IDUS:

eccentric wall thickening with an irregular luminal surface, disruption of the bile duct wall layered structure, and a hypoechoic mass with irregular margins

IgG-4 Cholangitis DD

IDUS: all bile duct layers inflamed, bile duct epithelium severely damaged, disappearance of the three layersImaging: diverticulum-like out-pouching, and beaded - tree appearance

INDUCTION 0,6-1 mg/kg oral prednisolone TAPERING 5 mg/wk reduction MAINTENANCE: 2,5-5 mg/die oral prednisolone or AZA Pancreatic enzyme supplementation (pancrelipasis) for exocrine insufficiency if: steatorrhoea, weight loss, metabolic bone disease, vitamin deficiency Oral hypoglicemic agents or insulin for diabetes mellitus Biliary stenting in obstructive jaundice (case-by-case)

Therapy

Outcomes

Spontaneous resolution in up to 30%

Response to steroid therapy in 90% to 95% with improvement of imaging findings and serology within 2 weeks + symptoms regression

New onset diabetes mellitus usually improves with corticosteroid therapy

Chronic pancreatitis

in about 10%

Very rarely

progression to cirrhosis in IgG-4 cholangitis

Outcomes

Response to steroid therapy in 90% to 95% of both parenchymal and ductal changes

Before (A) steroid therapy and after (B)

Suspect!May have acute or chronic manifestationTypical imaging findings (CT/MRI)Mandatory is exclusion of carcinomaCharacteristic histopathological appearance: histology is the GOLD STANDARDNot always elevated IgG and IgG-4 levelsSystemic disease: look for biliary and retroperitoneal involvement

TAKE HOME MESSAGES

Stone J, Zen Y. IgG4-Related Disease N Engl J Med 2012; 366: 539-51. Kamisawa T, Zen Y. Advances in IgG4-related pancreatobiliary diseases. Lancet Gastroenterol Hepatol 2018; 3: 575–85. Sandrasegaran K, Menias C. Imaging in Autoimmune Pancreatitis and Immunoglobulin G4–Related Disease of the Abdomen. Gastroenterol Clin N Am. 2018. Article in press.

Bibliografia