Summary
Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that typically manifests with obstructive jaundice and mild epigastric pain. It is characterized by lymphoplasmacytic infiltrate, fibrosis, and a strong response to glucocorticoid therapy. There are two subtypes of AIP. Type 1 AIP is the pancreatic manifestation of systemic IgG4-related disease, typically affecting older men, and it is associated with other organ involvement. Type 2 AIP is a pancreas-specific disorder, often seen in younger individuals, with no sex predominance, and it is frequently associated with inflammatory bowel disease, especially ulcerative colitis. The diagnosis is based on a combination of imaging findings (e.g., a sausage-shaped pancreas), serum IgG4 levels, histology, and response to glucocorticoids. The primary goal is to differentiate AIP from pancreatic cancer. Management for symptomatic patients involves inducing remission with glucocorticoids, followed by a tapering schedule. Maintenance therapy may be considered for type 1 AIP to prevent relapse.
Definitions
AIP is a form of pancreatitis characterized by obstructive jaundice, a dense lymphoplasmacytic infiltrate and fibrosis on histology, and a notable response to glucocorticoid therapy. [1][2]
- Type 1 AIP (also called lymphoplasmacytic sclerosing pancreatitis): considered the pancreatic manifestation of IgG4-related disease (IgG4-RD) [1][2]
- Type 2 AIP (also called idiopathic duct-centric pancreatitis or AIP with granulocyte epithelial lesions): often coexists with inflammatory bowel disease [1][3]
Epidemiology
-
Type 1 AIP
- Mean age at diagnosis: > 60 years [2]
- ♂ > ♀ (approx. 3:1) [2]
- Higher prevalence in East Asia (e.g., Japan) [4]
-
Type 2 AIP
- Mean age at diagnosis: 40 years [2]
- ♂ = ♀ [2]
- Higher prevalence in Europe and North America [3][4]
Epidemiological data refers to the US, unless otherwise specified.
Etiology
The exact pathogenesis of AIP is not fully understood and is likely multifactorial.
- Genetic predisposition [2]
-
Potential immunologic triggers [2]
- Autoimmunity: Autoantibodies against pancreatic enzymes (e.g., carbonic anhydrase II, lactoferrin) are often present.
- Molecular mimicry: immune response to pathogens may cross-react with pancreatic antigens
- Prolonged exposure to, e.g., industrial dust, solvents, or oils may contribute.
Clinical features
Common symptoms [1][3]
- Painless obstructive jaundice
- Mild epigastric pain (more common in type 2 AIP)
- Weight loss
- Clinical features of diabetes mellitus
- Signs and symptoms of exocrine pancreatic insufficiency
Subtype-specific features
-
Type 1 AIP [1][3]
- Insidious onset with a relapsing-remitting course
- Other manifestations of IgG4-related disease (e.g., sclerosing cholangitis, sialadenitis, tubulointerstitial nephritis, periaortitis)
-
Type 2 AIP
- Acute onset, often manifesting as recurrent acute pancreatitis [2]
- Associated with inflammatory bowel disease, most commonly ulcerative colitis [4]
Diagnosis
Approach [1][3][5]
- Consider AIP in patients with unexplained pancreatic enlargement or obstructive jaundice.
- Exclude pancreatic ductal adenocarcinoma and other causes of pancreatitis.
- Obtain cross-sectional imaging (CT or MRI).
- Laboratory studies support the diagnosis but are nonspecific.
- Refer for endoscopic ultrasound-guided biopsy if malignancy cannot be excluded or histologic confirmation is needed.
- Assess for clinical and radiological improvement after glucocorticoid therapy once cancer has been ruled out. [2][3]
The diagnosis of AIP is based on pancreatic imaging, serum IgG4 levels, other organ involvement, histopathology, and response to glucocorticoids. [4][5]
Imaging [1]
-
Cross-sectional imaging (CT or MRI)
- Diffuse enlargement: sausage-shaped pancreas with loss of lobular contour [2]
- Focal enlargement: may mimic pancreatic cancer
- Hypovascular enhancement (pancreatic phase) and homogeneous enhancement (delayed phase)
- Capsule-like rim (highly specific for AIP) [2]
-
MRCP or ERCP
- Main pancreatic duct narrowing: long (more than one-third of the duct) or multifocal strictures [2]
- No significant upstream dilatation
- Bile duct stenosis
- FDG-PET: increased uptake in pancreatic and extrapancreatic lesions
Laboratory studies [1]
-
Serum IgG4
- Typically increased in type 1 AIP; normal in type 2 AIP
- Nonspecific; may be mildly elevated in pancreatic cancer
-
Nonspecific studies [1][3]
- ↑ Liver enzymes and total bilirubin
- ↑ Pancreatic enzymes
- Normal or slightly elevated inflammatory markers [3]
-
Type 1 AIP
- Autoantibodies (e.g., ANA, RF, anti-carbonic anhydrase II, and anti-lactoferrin) may be positive.
- Polyclonal hypergammaglobulinemia, peripheral eosinophilia may be seen.
Biopsy [1][4]
-
Indications
- Diagnostic uncertainty after cross-sectional imaging and laboratory studies
- Concern for pancreatic cancer
- Preferred method: endoscopic ultrasound-guided fine-needle biopsy
-
Histopathology
- Type 1 AIP: marked lymphoplasmacytic infiltration, > 10/HPF IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis
- Type 2 AIP: neutrophilic infiltration of the pancreatic duct epithelium, forming granulocytic epithelial lesions [2]
Differential diagnoses
The differential diagnoses listed here are not exhaustive.
Management
General principles [1]
- Refer to gastroenterology for management.
- Glucocorticoids are the primary therapy for induction and maintenance of remission.
- Periodically measure serum IgG4 levels and obtain cross-sectional imaging for early detection of relapse.
Pharmacological treatment [1]
-
Indications [4]
- Symptomatic patients (e.g., obstructive jaundice, epigastric pain, fever)
- Presence of symptomatic extrapancreatic lesions in type 1 AIP
- Asymptomatic patients with IgG4-related sclerosing cholangitis and a persistent pancreatic mass or persistent elevated liver enzymes
-
Induction of remission
- Glucocorticoids (e.g., prednisolone for 2–4 weeks) [3][4]
- Taper by 5 mg every 1–2 weeks over the subsequent 2–3 months. [1]
-
Maintenance therapy [1]
- Indication: patients at high risk of relapse (e.g., diffuse pancreatic enlargement, proximal bile duct lesions, multiple extrapancreatic lesions, and persistently high serum IgG4) [1][3]
- Agent: prednisolone for 3 years [1]
- Not usually necessary in patients with type 2 AIP
-
Relapse management
- Resume glucocorticoids at the initial induction dose. [1][2]
- Alternate agents for patients with resistance to or dependence on glucocorticoids [1][2]
- Rituximab
- Immunomodulators (e.g., azathioprine, 6-mercaptopurine, mycophenolate mofetil)
A lack of response to glucocorticoids can be a sign of an incorrect diagnosis and should prompt further evaluation.
Complications
- Pancreatic exocrine dysfunction [1]
- Pancreatic endocrine dysfunction [1]
- Pancreatic atrophy [2]
- Pancreatic duct stones [2]
We list the most important complications. The selection is not exhaustive.
Prognosis
Relapse is common in patients with type 1 AIP and rare in patients with type 2 AIP. [1]
- Most patients achieve remission with glucocorticoid therapy.
- Patients with repeated relapses are at risk of chronic pancreatitis and pancreatic dysfunction.
- Some patients may achieve spontaneous remission (e.g., those without obstructive jaundice).