Autoimmune pancreatitis

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis associated with autoimmune manifestations on clinical, histological and laboratory grounds ¹.

Distinguishing this entity from other forms of chronic pancreatitis (such as alcohol) is important as steroid treatment is effective both in reversing morphologic changes but also to return pancreatic function to normal ².

Definition

Type of chronic pancreatitis characterised by a heterogenous autoimmune inflammatory process in which prominent lymphocytic infiltration with associated fibrosis of the pancreas causes organ dysfunction.

Diagnostic criteria have been established ^3,8, see Diagnostic criteria for autoimmune pancreatitis.

Epidemiology

The condition is rare, with an exact incidence unknown but with increasing number cases reported in the literature ³. It is thought to account for 5-11% of chronic pancreatitis cases.

Age of presentation is variable, and there appears to be a male predilection (male to female ratio is 2:1) ³.

Clinical presentation

Clinical presentation is also variable, including ^3,7:

• jaundice
• weight loss
• new onset diabetes
• extrapancreatic manifestations, with lymphocytic infiltration
  • inflammatory bowel disease
  • pulmonary involvement
  • renal involvement
  • biliary tree
  • salivary glands
• abdominal pain and acute pancreatitis are unusual

Sometimes serum amylase and lipase are raised as well as raised Alkaline phosphatase.

Raised IgG and antinuclear antibody levels seen in greater than 50% of cases.

Pathology

Cause unknown though there is a strong basis for an autoimmune process where antibody reaction against carbonic anhydrase and lactoferrin has been postulated ⁹. 

Macroscopic findings 

Diffusely indurated and firm pancreas, with some patients demonstrating a focal mass.

Histological Hallmarkhallmark

Collar like periductal infiltrate composed of lymphocytes and plasma cells ⁴, with the lymphocytes being CD 8+ and CD 4+ T lymphocytes.

Clusters of inflammatory cells also seen in the walls of small veins and nerves as well as medium and large sized vessels.

Interlobular septa are thickened by a proliferation of myofibroblasts and infiltrated by lymphocytes and plasma cells.

Other organs can also be involved with a lymphocytic infiltrate: GB, biliary tree, kidney, lung and salivary glands more commonly.

Associations

• IgG4 related sclerosing disease ^11-12
• rheumatoid arthritis
• Sjögren syndrome
• inflammatory bowel disease (IBD)
• sclerosing cholangitis
• In Japanese: haplotypes DRB1 and DQB1

Radiograhphic features

CT

• diffuse or focal enlargement of the pancreas with loss of definition of pancreatic clefts
• minimal peripancreatic fat stranding, with inflammatory thickening confined to the peripancreatic region not extending into the mesentery, anterior pararenal fascia or lateroconal fascia
• peripancreatic rim of low attenuation "halo" ⁵
• when focal involvement - typically head and uncinate process and may be iso to hypo to pancreatic tissue
• pancreas can appear normal
• pancreatic dilatation may be seen as can biliary dilatation

Contrast enhancement is helpful as autoimmune pancreatitis demonstrates reduced enhancement during the pancreatic phase (~40 seconds) but near normal enhancement at portal venous phase (70 seconds) ⁶.

Other sites also seen to be involved:

• peripancreatic lymph-nodes >1 cm
• kidney: inflammatory pseudotumours: hypoattenuating lesions
• retroperitoneal fibrosis: with periaortic soft tissue
• pleural effusions
• CBD: strictures
• mediastinal nodes

MRI

MRI demonstrates diffuse pancreatic enlargement  ^5,10.

• T1: decreased signal intensity
• T2: minimal increase in signal intensity
• C+ (Gd): delayed parenchymal enhancement on dynamic imaging.

MRCP: multiple intrahepatic duct strictures and common bile duct; diffuse narrowing of the main pancreatic duct

ERCP

Can be normal.

Biliary duct abnormalities are common with strictures of the CBD and short intrahepatic duct strictures representing PSC.

Diffuse irregularity and narrowing of the main pancreatic duct (as distinct from pancreatic carcinoma).

Treatment and prognosis

Treatment is with steroids usually leads to resolution both of morphological changes and a return to normal pancreatic function, with remission seen in 98% of cases ⁷. The condition is however also frequently self limiting, with spontaneous remission rate of up to 74% ⁷.

Relapse rates high, seen in 24% of patients treated with steroids. The rate is higher in untreated patients ⁷.

Autoimmune pancreatits accounts for 2-6% of patients who undergo pancreatic resection because they are suspected of having pancreatic cancer ^5,10.

Etymology

It was first described in 1995 by Yoshida et al¹.

Differential diagnosis

For the diffuse form consider:

• lymphoma
• plasmacytoma
• pancreatic metastases
• diffuse infiltrative pancreatic ductal adenocarcinoma

In these conditions, the pancreas is heterogeneously enhancing and an irregular pancreatic contour is seen.

For the focal form consider:

• pancreatic ductal adenocarcinoma
  • adenocarcinomas tend to have minimal enhancement both on pancreatic (late arterial, ~40 seconds) and hepatic phase imaging, whereas autoimmune pancreatitis demonstrates near normal enhancement during hepatic phase (portal venous, ~70 seconds) ⁶