(AIP)

ARIEL YUDKOVICH
Introduction
• AIP is a distinct form of chronic pancreatitis characterized
• Clinically by frequent presentation with obstructive jaundice with or
without a pancreatic mass
• Histologically by a lymphoplasmacytic infiltrate and fibrosis
• Therapeutically by a dramatic response to steroids

• When thus defined, AIP has two distinct subtypes

• Type 1 and Type 2.
Type 1 AIP
Pancreatic manifestation of a multi-focal systemic disease, called IgG4-
Related Disease (IgG4-RD)

• IgG4-RD is characterized by:

• Fibro-inflammatory process
• Elevated serum IgG4 levels
• Typical histopathology in pancreas as well as other organs
• Tissue infiltration with IgG4 positive cells
Type 2 AIP
• Pancreas-specific disease that is not associated with elevated serum
IgG4 or infiltration of tissues with IgG4 positive cells
• Presence of “granulocyte epithelial lesions (GEL)” in pancreatic ducts
• Approximately 20 to 30% patients also have IBD
 Histological findings in autoimmune pancreatitis

a Type 2: duct with granulocytic epithelial lesion .

b Type 2: periductal area without IgG4-positive plasma cells.
c Type 1: duct with periductal lymphoplasmacytic infiltration.
d Type 1: periductal accumulation of IgG4-positive plasma cells

Journal of Gastroenterology 2010

European Journal of Gastroenterology and Hepatology
Volume 3, Issue 2 / June 2017
Association with other disorders
AIP can occur as a primary pancreatic disorder or in association with
other disorders with autoimmune etiology including:
• IgG4 cholangitis
• salivary gland disorders
• mediastinal fibrosis
• retroperitoneal fibrosis
• tubulointerstitial disease
• inflammatory bowel disease
Epidemiology
• AIP is rare with estimated prevalence of <1 per 100,000 in the general
population.
• Although uncommon, AIP is a globally recognized disease.
• With large published series from Asia, Europe, and North America.
• Male predominance 3:1 and older than 50 years of age.
• If associated with other autoimmune disorders, it may present at a
younger age.
Pathogenesis of AIP
• Immunologic mechanisms appear to be the cause, given the characteristic
histologic findings of:
• lymphoplasmacytic infiltration (the hallmark of the disease).
• prevalence of hypergammaglobulinemia.
• autoantibodies.
• response to steroids.
• Other antibodies, including antinuclear, anti-smooth muscle, antihuman lactoferrin, and anti-
carbonic anhydrase II antibodies have been described in patients with AIP.
• none of them proved to be specific or sensitive.

• Like other autoimmune diseases, AIP is associated with a particular HLA

serotypes, DRB1 0405 and DQB 0401.
Pathogenesis OF AIP
• Elevated levels of gammaglobulins is a characteristic finding.
• 9 Ig isotypes IgM, IgD, IgE, IgG (four subclasses IgG1, IgG2, IgG3 and IgG4) and IgA
(subclasses IgA1 and IgA2).
• IgG4 accounts for 3 to 6 of total IgG in normal subjects.
• Elevated levels of the IgG4 subclass is a sensitive and specific marker for AIP but
not for:
• pancreas cancer
• chronic pancreatitis
• PSC or PBC.
• With steroid therapy these levels decrease, but do not normalize in most patients
with AIP.
Hypothesis for the pathogenesis of AIP and IgG4-related disease

Journal of Hepatology 61(3) · April 2014

Clinical presentation of AIP
• The most common clinical symptom is obstructive jaundice, which is
painless in 50-70% of patients
• Anorexia and weight loss
• Diabetes Mellitus -- up to 76%
• Mild abdominal pain
.
Diagnosis of AIP
• Autoimmune pancreatitis (AIP) should be considered in the
differential diagnosis of patients presenting with the varied symptoms
referable to the pancreas and biliary tract described above,
particularly in those with other autoimmune conditions.
• Correct diagnosis can help avert the consequences of progressive
disease and unnecessary surgery.
• An important part of the differential diagnosis is distinguishing AIP
from pancreatic cancer.
Diagnosis of AIP
• The diagnostic criteria proposed by the Mayo Clinic ("HISORt") is
most commonly used in the United States it includes the presence of
one or more of the following:
• Diagnostic Histology
• Characteristic Imaging on computed tomography (CT) and/or
pancreatography
• Elevated serum IgG4 levels on Serologic testing
• Other organ involvement (see 'Other manifestations' above)
• Response of pancreatic and extrapancreatic manifestations to glucocorticoid
therapy
AIP characteristic on computed tomography
(CT)
AIP on Endoscopic retrograde
cholangiopancreatography (ERCP)

Endoscopic retrograde cholangiopancreatography in a patient with autoimmune

pancreatitis. The left panel shows a stricture in the common bile duct due to the
surrounding enlarged pancreas (long arrow). The right panel shows a stent that has
been inserted across the narrowed segment (short arrow).
Treatment for AIP
• Glucocorticoids treatment with prednisone at a dosage of 40 mg/day for
four to six weeks followed by a taper of 5 mg/week.
• Toward the end of the four- to six-week induction period, we perform
repeat imaging tests to evaluate for radiologic improvement.
• Failure to respond in this timeframe should raise the possibility of
alternative diagnoses.
• Patients who relapse upon a reduction and/or discontinuation of
glucocorticoids can be managed with a repeat course and/or maintenance
therapy aiming for the minimum glucocorticoid dose that provides a
maintained response (typically in range of 10 mg of prednisone daily).
Treatment for AIP
• An incomplete response and/or relapse is more likely in patients who
have biliary strictures.
• In patients with coexisting immunoglobulin G4-associated cholangitis,
we use azathioprine 2 mg/kg.
• We also consider immunomodulators in AIP patients without IgG4
cholangitis who fail steroid.
International Consensus Diagnostic Criteria (ICDC) for AIP

This algorithm is based on eastern and western experts' opinions to recommend standard treatment of AIP
worldwide. As medical insurance systems are different in each country, it can be tailored depending on local
expertise.

International Association of Pancreatology (IAP) 2016.

SUMMARY
• Autoimmune pancreatitis is a recently described
disorder presenting with mild epigastric discomfort and
jaundice.
• Patients may have associated autoimmune disorders
and autoantibodies.
• Imaging shows diffuse or focal pancreatic enlargement,
and pancreatic duct and bile duct stenoses.
• There is a low level of awareness of AIP, high index of
suspicion inthe correct clinical setting is necessary to
make a diagnosis.
• Steroid therapy is almost always effective
• AIP is clinically important since it is treatable, and may
be mistakenfor pancreatic carcinoma.
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