Pancreatitis, Autoimmune

Pancreatitis, Autoimmune

 

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis characterized by a diffuse enlargement of the pancreas, narrowing of the pancreatic duct, lymphoplasmacytic infiltration and fibrosis, increased serum IgG4 and response to steroid treatment.

Epidemiology

  • Incidence – rare, 5-6% of patients with chronic pancreatitis
  • Age – most are >50 years at onset
  • Gender – More prevalent in males than females

Pathophysiology

  • Histologic hallmark is collar-like preductal infiltrates composed of lymphocytes and plasma cells termed lymphoplasmacytic sclerosing pancreatitis (LPSP)
    • Other organs may be involved including the gallbladder, bile ducts, kidney, lung and salivary glands
    • IgG4 positive plasma cells have been identified in some patients

Clinical Presentation

  • AIP may coexist in about 40-60% of patients with autoimmune diseases such as Sjögren’s syndrome, primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC), suggesting that common targets in the pancreas or exocrine organs such as the salivary gland or biliary tract may be involved in disease pathogenesis
  • Pancreatic
    • Obstructive jaundice
    • Abdominal pain
    • Diabetes
    • Weight loss
  • Extrapancreatic
    • Pulmonary – discrete nodules, diffuse infiltrate, hilar adenopathy
    • Renal – lesions, mild renal insufficiency

Diagnosis

  • No consensus diagnostic criteria for autoimmune pancreatitis has been established
  • Current diagnostic criteria for autoimmune pancreatitis includes the following:
    • Diagnostic criteria for autoimmune pancreatitis by the Japan Pancreas Society
    • Kim diagnostic criteria for autoimmune pancreatitis (Korea)
    • HISORt diagnostic criteria for autoimmune pancreatitis (Mayo, USA)
    • Diagnostic criteria for autoimmune pancreatitis by the Italian group
  • Although significant differences exist between these criteria, overlaps occur in certain aspects
  • The most comprehensive diagnostic criteria is that from the Japanese group
    • The Japanese diagnostic criteria for AIP require the presence of imaging together with a laboratory and/or a histopathological finding
Diagnostic Criteria for Autoimmune Pancreatitis
Findings on Imaging Radiography

(One Required)

 Serologic and Histologic Findings (One Required)
Cross-Sectional Imaging ERCP or MRCP Serologic Analysis Pancreatic-Biliary Histologic Analysis Nongastrointestinal Histologic Analysis
Diffusely enlarged pancreas Segmental pancreatic ductal narrowing Elevated serum IgG4 level Periductal lymphoplasmacytic infiltration or fibrosis Tubulointerstitial nephritis with immune deposits within tubular basement membranes
Enhanced peripheral rim of hypoattenuation “halo” Focal pancreatic ductal narrowing Elevated serum IgG or gamma globulin level Obliterative phlebitis Pulmonary interstitial lymphoplasmacytic infiltration with IgG4-positive plasma cells*
Low-attenuation mass in head of pancreas Diffuse pancreatic ductal narrowing Presence of ALA, ACA II, ASMA, or ANA IgG4-positive plasma cells in tissue* Chronic sialadenitis with IgG4-positive plasma cells*
Criteria were modified from those of the Japan Pancreas Society. ERCP denotes endoscopic retrograde cholangiopancreatography, MRCP magnetic resonance cholangiopancreatography, ALA antilactoferrin antibody, ACA II anti-carbonic anhydrase II antibody, ASMA anti-smooth muscle antibody and ANA antinuclear antibody.
*The presence of tissue IgG4-positive cells is not necessarily abnormal, but an increased number of infiltrating IgG4-positive plasma cells is abnormal. 
(Used with permission from Finkelberg, 2006, 2674)
  • Imaging
    • Ultrasound/CT/MRI
    • Endoscopic retrograde cholangiopancreatography (ECRP)
  • Laboratory Testing
    • IgG, IgG4 testing
    • Consider autoantibodies testing
      • Antilactoferrin (ALA), anti-carbonic anhydrase (ACA), antismooth muscle (ASMA), antinuclear antibodies (ANA)
  • Histology
    • Characterized by lymphocyte and plasma cell infiltration
    • Important in differentiating AIP from acute and chronic pancreatitis, lymphoma and pancreatic cancer

Differential Diagnosis

  • Pancreatic or biliary cancer
    • Primary sclerosing cholangitis (PSC)
    • Primary biliary cirrhosis (PBC)
    • Inflammatory bowel diseases (ulcerative colitis, Crohn’s disease)
    • Sjögren syndrome
    • Rheumatoid arthritis
    • Autoimmune thyroid diseases

Treatment

  • Steroids
    • Positive response to steroids confirms diagnosis

See Also