Autoimmune pancreatitis
Encyclopedia
Autoimmune pancreatitis (AIP) is an increasingly recognized type of chronic pancreatitis
that can be difficult to distinguish from pancreatic carcinoma but which responds to treatment with corticosteroids, particularly prednisone
. It is increasingly regarded as a form of hyper-IgG4 disease.
(IgG), or IgG4, (3) the presence of serum autoantibodies such as anti-nuclear antibody
(ANA), anti-lactoferrin
antibody, anti-carbonic anhydrase
II antibody, and rheumatoid factor
(RF), (4) a diffusely enlarged pancreas, (5) diffuse irregular narrowing of the main pancreatic duct and stenosis of the intrapancreatic bile duct on endoscopic retrograde cholangiopancreatography
(ERCP), (6) rare pancreatic calcification or cyst formation, and (7) marked responsiveness to treatment with corticosteroids. AIP is sometimes associated with other autoimmune disorders, most commonly Sjögren's syndrome
, primary sclerosing cholangitis
(PSC), and inflammatory bowel disease
. AIP occurring in association with an autoimmune disorder has been referred to as “secondary” or “syndromic” AIP.
For diagnosis, criterion I (pancreatic imaging) must be present with criterion II (laboratory data) and/or III (histopathologic findings).
- or CD8
-positive lymphocytes and IgG4-positive plasma cells, and exhibits interstitial fibrosis and acinar cell
atrophy in later stages. at the initial stages, typically, there is a cuff of lymphoplasma cells surrounding the ducts but also more diffuse infiltration in the lobular parenchyma. However, localization and the degree of duct wall infiltration are variable. Whereas histopathologic examination remains the primary method for differentiation of AIP from acute and chronic pancreatitis, lymphoma
, and cancer. By Fine Needle Aspiration (FNA) the dignosis can be made if adequate tissue is obtained. In such cases lymphoplasmacytic infiltration of the lobules are the key finding. Rarely, granulomatous reaction could be observed. It has been proposed that a cytologic smear primarily composed of acini rich in chronic inflammatory cells (lymphocytes, plasma cells), with rare ductal epithelial cells lacking atypia, favors the diagnosis of AIP. The sensitivity and the specificity of these criteria for differentiating AIP from neoplasia are unknown.
In cases of systemic manifestion of AIP, the pathologic features would be similar in other organs.
Computed tomography
(CT) findings in AIP include a diffusely enlarged hypoechoic pancreas or a focal mass that may be mistaken for a pancreatic malignancy. A low-density, capsule-like rim on CT (possibly corresponding to an inflammatory process involving peripancreatic tissues) is thought to be an additional characteristic feature. Magnetic resonance imaging
(MRI) reveals a diffusely decreased signal intensity and delayed enhancement on dynamic scanning. The characteristic ERCP finding is segmental or diffuse irregular narrowing of the main pancreatic duct, usually accompanied by an extrinsic-appearing stricture of the distal bile duct. Changes in the extrapancreatic bile duct similar to those of primary sclerosing cholangitis
(PSC) have been reported.
The role of endoscopic ultrasound
(EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of AIP is not well described, and EUS findings have been described in only a small number of patients. In one study, EUS revealed a diffusely swollen and hypoechoic pancreas in 8 of the 14 (57%) patients, and a solitary, focal, irregular mass was observed in 6 (46%) patients. Whereas EUS-FNA is sensitive and specific for the diagnosis of pancreatic malignancy, its role in the diagnosis of AIP remains unclear.
, or inflammatory bowel disease
. Some of the earliest cases were reported as pancreatic pseudotumor or pseudolymphoma.
for a benign disease which responds well to medical therapy.
Chronic pancreatitis
Chronic pancreatitis is a long-standing inflammation of the pancreas that alters its normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption....
that can be difficult to distinguish from pancreatic carcinoma but which responds to treatment with corticosteroids, particularly prednisone
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
. It is increasingly regarded as a form of hyper-IgG4 disease.
Clinical features
AIP is characterized by the following features: (1) mild symptoms (abdominal pain, weight loss, nausea), usually without acute attacks of pancreatitis, (2) increased serum levels of gamma globulins, immunoglobulin GImmunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
(IgG), or IgG4, (3) the presence of serum autoantibodies such as anti-nuclear antibody
Anti-nuclear antibody
Anti-nuclear antibodies are autoantibodies directed against contents of the cell nucleus....
(ANA), anti-lactoferrin
Lactoferrin
Lactoferrin , also known as lactotransferrin , is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions...
antibody, anti-carbonic anhydrase
Carbonic anhydrase
The carbonic anhydrases form a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons , a reversible reaction that occurs rather slowly in the absence of a catalyst...
II antibody, and rheumatoid factor
Rheumatoid factor
Rheumatoid factor is an autoantibody most relevant in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG. RF and IgG join to form immune complexes that contribute to the disease process...
(RF), (4) a diffusely enlarged pancreas, (5) diffuse irregular narrowing of the main pancreatic duct and stenosis of the intrapancreatic bile duct on endoscopic retrograde cholangiopancreatography
Endoscopic retrograde cholangiopancreatography
Endoscopic retrograde cholangiopancreatography is a technique that combines the use of endoscopy and fluoroscopy to diagnose and treat certain problems of the biliary or pancreatic ductal systems...
(ERCP), (6) rare pancreatic calcification or cyst formation, and (7) marked responsiveness to treatment with corticosteroids. AIP is sometimes associated with other autoimmune disorders, most commonly Sjögren's syndrome
Sjögren's syndrome
Sjögren's syndrome , also known as "Mikulicz disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva....
, primary sclerosing cholangitis
Primary sclerosing cholangitis
Primary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...
(PSC), and inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
. AIP occurring in association with an autoimmune disorder has been referred to as “secondary” or “syndromic” AIP.
Diagnostic criteria
In 2002, the Japanese Pancreas Society proposed the following diagnostic criteria for autoimmune pancreatitis:-
- I. Pancreatic imaging studies show diffuse narrowing of the main pancreatic duct with irregular wall (more than 1/3 of length of the entire pancreas).
- II. Laboratory data demonstrate abnormally elevated levels of serum gamma globulin and/or IgG, or the presence of autoantibodies.
- III. Histopathologic examination of the pancreas shows fibrotic changes with lymphocyteLymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
and plasma cellPlasma cellPlasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells which produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system...
infiltrate.
For diagnosis, criterion I (pancreatic imaging) must be present with criterion II (laboratory data) and/or III (histopathologic findings).
Histopathology
Histopathologic examination of the pancreas reveals a characteristic lymphoplasmacytic infiltrate of CD4CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
- or CD8
CD8
CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...
-positive lymphocytes and IgG4-positive plasma cells, and exhibits interstitial fibrosis and acinar cell
Acinar cell
Acinar cell may refer to:* Centroacinar cells of the pancreas* Other acinus cells...
atrophy in later stages. at the initial stages, typically, there is a cuff of lymphoplasma cells surrounding the ducts but also more diffuse infiltration in the lobular parenchyma. However, localization and the degree of duct wall infiltration are variable. Whereas histopathologic examination remains the primary method for differentiation of AIP from acute and chronic pancreatitis, lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
, and cancer. By Fine Needle Aspiration (FNA) the dignosis can be made if adequate tissue is obtained. In such cases lymphoplasmacytic infiltration of the lobules are the key finding. Rarely, granulomatous reaction could be observed. It has been proposed that a cytologic smear primarily composed of acini rich in chronic inflammatory cells (lymphocytes, plasma cells), with rare ductal epithelial cells lacking atypia, favors the diagnosis of AIP. The sensitivity and the specificity of these criteria for differentiating AIP from neoplasia are unknown.
In cases of systemic manifestion of AIP, the pathologic features would be similar in other organs.
CT, MRI, and ERCP
Computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT) findings in AIP include a diffusely enlarged hypoechoic pancreas or a focal mass that may be mistaken for a pancreatic malignancy. A low-density, capsule-like rim on CT (possibly corresponding to an inflammatory process involving peripancreatic tissues) is thought to be an additional characteristic feature. Magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) reveals a diffusely decreased signal intensity and delayed enhancement on dynamic scanning. The characteristic ERCP finding is segmental or diffuse irregular narrowing of the main pancreatic duct, usually accompanied by an extrinsic-appearing stricture of the distal bile duct. Changes in the extrapancreatic bile duct similar to those of primary sclerosing cholangitis
Primary sclerosing cholangitis
Primary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...
(PSC) have been reported.
EUS, and EUS-FNA
The role of endoscopic ultrasound
Endoscopic ultrasound
Endoscopic ultrasound or echo-endoscopy is a medical procedure in endoscopy is combined with ultrasound to obtain images of the internal organs in the chest and abdomen. It can be used to visualize the wall of these organs, or to look at adjacent structures...
(EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of AIP is not well described, and EUS findings have been described in only a small number of patients. In one study, EUS revealed a diffusely swollen and hypoechoic pancreas in 8 of the 14 (57%) patients, and a solitary, focal, irregular mass was observed in 6 (46%) patients. Whereas EUS-FNA is sensitive and specific for the diagnosis of pancreatic malignancy, its role in the diagnosis of AIP remains unclear.
Controversies in nomenclature
As the number of published cases of AIP has increased, efforts have been focused on defining AIP as a distinct clinical and pathologic entity and toward developing some generally agreed upon diagnostic criteria and nomenclature. Terms frequently encountered are autoimmune or autoimmune-related pancreatitis, lymphoplasmacytic sclerosing pancreatitis, idiopathic tumefactive chronic pancreatitis, idiopathic pancreatitis with focal irregular narrowing of the main pancreatic duct, and non-alcoholic duct destructive chronic pancreatitis. There are also a large number of case reports employing descriptive terminology such as pancreatitis associated with Sjögren’s syndrome, primary sclerosing cholangitisPrimary sclerosing cholangitis
Primary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...
, or inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
. Some of the earliest cases were reported as pancreatic pseudotumor or pseudolymphoma.
Treatment
AIP often completely resolves with steroid treatment. The failure to differentiate AIP from malignancy may lead to unnecessary pancreatic resection, and the characteristic lymphoplasmacytic infiltrate of AIP has been found in up to 23% of patients undergoing pancreatic resection for suspected malignancy who are ultimately found to have benign disease. In this subset of patients, a trial of steroid therapy may have prevented a Whipple procedure or complete pancreatectomyPancreatectomy
In medicine, a pancreatectomy is the surgical removal of all or part of the pancreas. Several types of pancreatectomy exist, including pancreaticoduodenectomy , distal pancreatectomy, segmental pancreatectomy, and total pancreatectomy...
for a benign disease which responds well to medical therapy.