Autoimmune pancreatitis: proposal of IgG4-related sclerosing disease

Abstract

Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of presumed autoimmune etiology. Many new clinical aspects of AIP have been clarified during the past 10 years, and AIP has become a distinct entity recognized worldwide. However, its precise pathogenesis or pathophysiology remains unclear. As AIP dramatically responds to steroid therapy, accurate diagnosis of AIP is necessary to avoid unnecessary surgery. Characteristic dense lymphoplasmacytic infiltration and fibrosis in the pancreas may prove to be the gold standard for diagnosis of AIP. However, since it is difficult to obtain sufficient pancreatic tissue, AIP should be diagnosed currently based on the characteristic radiological findings (irregular narrowing of the main pancreatic duct and enlargement of the pancreas) in combination with serological findings (elevation of serum gamma-globulin, IgG, or IgG4, along with the presence of autoantibodies), clinical findings (elderly male preponderance, fluctuating obstructive jaundice without pain, occasional extrapancreatic lesions, and favorable response to steroid therapy), and histopathological findings (dense infiltration of IgG4-positive plasma cells and T lymphocytes with fibrosis and obliterative phlebitis in various organs). It is apparent that elevation of serum IgG4 levels and infiltration of abundant IgG4-positive plasma cells into various organs are rather specific to AIP patients. We propose a new clinicopathological entity, "IgG4-related sclerosing disease", and suggest that AIP is a pancreatic lesion reflecting this systemic disease.

Fig. 1a–f

Radiological findings of patients with autoimmune pancreatitis. a Diffuse enlargement of the pancreas showing delayed enhancement on computed tomography scan. b A hypointense capsule-like rim surrounding the swollen pancreas on a T2-weighted magnetic resonance image. c Diffuse hypoechoic swollen pancreas with hyperechoic spots on US. d Diffuse irregular narrowing of the main pancreatic duct on endoscopic retrograde pancreatography. Degree of narrowing varies. e Stenosis of the lower bile duct and segmental narrowing of the main pancreatic duct of the pancreatic head on endoscopic retrograde cholangiopancreatography. Upstream dilatation of the distal pancreatic duct is less noted than with pancreatic cancer. f After steroid therapy, both stenosis of the bile duct and narrowing of the main pancreatic duct (e) improved

Fig. 2a–c

Histological findings of the pancreas of patients with autoimmune pancreatitis. a Prominent periductal and interlobular fibrosis with a dense lymphoplasmacytic infiltration and acinar destruction (hematoxylin-eosin stain) b Pancreatic duct narrowed by periductal nonocclusive fibrosis and lymphoplasmacyticinfiltration (elastica-van Gieson stain) c Obliterative phlebitis of the pancreatic veins with prominent lymphoplasmacytic infiltrate and fibrosis (elastica-van Gieson stain)

Fig. 3a–e

IgG4-immunostaining of various organs of patients with autoimmune pancreatitis. Dense infiltration of IgG4-positive plasma cells was detected in the pancreas (a), periportal area of the liver (b), salivary gland (c), lymph node (d), and associated retroperitoneal fibrous mass (e)

Fig. 4

Schematic illustration showing the relationship between IgG4-related sclerosing disease, autoimmune pancreatitis, sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis, and pseudotumor