Autoimmune pancreatitis

Defintion

Autoimmune pancreatitis (AIP) is an uncommon but well-established form of pancreatic inflammation. Unlike other pancreatic diseases, it typically has a dramatic response to glucocorticoid therapy.

Presentation

• Acute pancreatitis
• If untreated, AIP can lead to chronic pain, pancreatic insufficiency, fibrosis, and other complications.

Types

Type 1 AIP

• Type 1 AIP is defined histologically as lymphoplasmacytic sclerosing pancreatitis (LPSP)
  • The International Consensus Diagnostic Criteria (ICDC) defined type 1 AIP as: dense infiltration of plasma cells and lymphocytes, particularly periductal; storiform (a swirling, “cartwheel” pattern) fibrosis; venulitis with lymphocytes and plasma cells, often leading to obliteration of the affected veins; and abundant (>10 cells per high-power field) immunoglobulin G4 (IgG4)-positive plasma cells.
• Type 1 AIP may present as an isolated disorder or as part of an IgG4-related disease (IgG4-RD) syndrome with other organ involvement (OOI).

Type 2 AIP 

• Type 2 AIP is defined histologically as idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocyte epithelial lesions (GELs).
  • The GEL lesions are intraluminal and intraepithelial neutrophils in medium-sized and small ducts as well as in acini, often leading to the destruction and obliteration of the duct lumen
  • IDCP usually has very few IgG4-positive plasma cells (<10 cells/HPF).
• Type 2 AIP appears to be limited to the pancreas and often co-occurs in patients with inflammatory bowel disease (IBD).

Diagnosis

• The discovery of an elevated serum immunoglobulin G4 (IgG4) as a biomarker of AIP helped establish the disorder as distinct from other forms of chronic pancreatitis; although, later studies demonstrated that IgG4 levels are often normal in AIP and that other diseases such as pancreatic cancer may be associated with moderately elevated IgG4 levels.

Imaging

• MRI/CT - Diffusely enlarged pancreas with featureless borders and delayed enhancement with or without a capsule-like rim
• MRCP -  delineate ductal abnormalities
• EUS - can be considered to rule out cancer
  • FNA

Parenchymal imaging	Typical: - Diffuse enlargement with delayed enhancement (sometimes associated with rim-like enhancement)	Indeterminate (including atypical*): - Segmental/focal enlargement with delayed enhancement
D	Ductal imaging (ERP)	Long (greater than one-third length of the main pancreatic duct) or multiple strictures without marked upstream dilatation	Segmental/focal narrowing without marked upstream dilatation (duct size, <5 mm)
S	Serology	IgG4, >2× upper limit of normal value	IgG4, 1 to 2× upper limit of normal value
OOI	Other organ involvement	1 or 2	1 or 2
		1. Histology of extrapancreatic organs Any three of the following: 1. Marked lymphoplasmacytic infiltration with fibrosis and without granulocytic infiltration 2. Storiform fibrosis 3. Obliterative phlebitis 4. Abundant (>10 cells/HPF) IgG4-positive cells 2. Typical radiologic evidence At least one of the following: 1. Segmental/multiple proximal (hilar/intrahepatic) or proximal and distal bile duct stricture 2. Retroperitoneal fibrosis	1. Histology of extrapancreatic organs including endoscopic biopsies of bile duct¶ Both of the following: 1. Marked lymphoplasmacytic infiltration without granulocytic infiltration 2. Abundant (>10 cells/HPF) IgG4-positive cells 2. Physical or radiologic evidence At least one of the following: 1. Symmetrically enlarged salivary/lachrymal glands 2. Radiologic evidence of renal involvement described in association with AIP
H	Histology of the pancreas	LPSP (core biopsy/resection)	LPSP (core biopsy/resection)
		At least 3 of the following: 1. Periductal lymphoplasmacytic infiltrate without granulocytic infiltration 2. Obliterative phlebitis 3. Storiform fibrosis 4. Abundant (>10 cells/HPF) IgG4-positive cells	Any 2 of the following: 1. Periductal lymphoplasmacytic infiltrate without granulocytic infiltration 2. Obliterative phlebitis 3. Storiform fibrosis 4. Abundant (>10 cells/HPF) IgG4-positive cells
Response to steroid (Rt)	Diagnostic steroid trial	Rapid (≤2 weeks) radiologically demonstrable resolution or marked improvement in pancreatic/extrapancreatic manifestations	Rapid (≤2 weeks) radiologically demonstrable resolution or marked improvement in pancreatic/extrapancreatic manifestations

Management

• Indicated in
  • Symptomatic patients
  • Asymptomatic patients with
    • Mass
    • Elevated liver enzymes
    • Progress IgG4-related disease lesions
    • Pancreatic failure
• Treatment
  • Glucocorticoids
    • prednisone at a dose of 40 mg per day for four to six weeks.
      • Repeat imaging near the end of treatment
      • Most patients who are going to respond will have done by then
      • Failure to respond should raise the possibility of an alternative diagnosis
    • Then taper the dose by 5mg per week over 2 months
    • Goal to discontinue entirely
  • Maintenance treatment
    • In patients at high risk of relapse
      • Type 1 AIP with diffuse enlargement of the pancreas
      • More than two OOIs or association with proximal IgG4-SC before treatment
      • Delayed radiologic remission with treatment
      • Persistently high serum IgG4 (>2 times upper limit of normal) after treatment \
    • Low-dose glucocorticoids
    • Immunomodulators (azathioprine or mycophenolate mofetil), or rituximab