Autoimmune Pancreatitis

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Diagnosis and reasoning

Jaundice is not a common symptom in adults, and should always raise concern of underlying serious disease. Key to the evaluation of these patients is determining if the jaundice is medical (i.e. hepatic or intra-hepatic) or surgical (post-hepatic) in origin; note that the associated epigastric pain radiating to the back favors the latter. The characteristics of the pain also suggest several likely causative etiologies - most prominently, acute pancreatitis or gallstone disease. His initial investigations should include a liver profile (including serum bilirubin levels), serum amylase and lipase, and an ultrasound scan of the abdomen. The liver profile reveals the presence of direct (i.e. conjugated) hyperbilirubinemia and markedly elevated alkaline phosphatase (ALP) levels, further suggesting that this is obstructive jaundice. In addition, the ultrasound scan shows no evidence of gallstones; however, the pancreas is found to be diffusely hypoechogenic. Diffuse hypoechogenicity of the pancreas is most closely associated with pancreatic inflammation (i.e. acute pancreatitis); however, both serum amylase and lipase are within normal parameters. Pancreatic malignancy can also give rise to this sonographic appearance; thus further imaging via contrast computerized tomography (CECT) is essential. The CECT study in turn reveals the presence of a 'sausage-shaped' pancreas with delayed rim enhancement, an unusual finding which is strongly suggestive of an entirely different etiology - autoimmune pancreatitis (AIP). While the above imaging findings are typical of AIP, they alone are insufficient for diagnose the condition; the International Consensus Diagnostic Criteria (ICDC) require the presence of concomitant serological or histological evidence as well. A serum immunoglobulin G4 (IgG4) assay is a good next step; this is found to be elevated more than twice the upper limit of normal, which the ICDC considers to be strongly suggestive of type 1 AIP. Thus, per the ICDC criteria, he should be started on corticosteroids (to which AIP is exquisitely responsive), and reassessed after 2 weeks; improvement of his clinical symptoms and biochemical parameters after this period will provide the final piece of evidence necessary to clinch the diagnosis. While patients with acute pancreatitis are usually kept nil per oral, this is not generally indicated in uncomplicated AIP; neither are antibiotic therapy or pancreatic duct sphincterotomy required.


Discussion

Autoimmune pancreatitis (AIP) is a rare, chronic inflammatory disease of the pancreas, which can occur independently, or as part of a systemic fibroinflammatory syndrome involving the biliary system, salivary glands, and lymph nodes. The overall prevalence of AIP in the United States is unclear; in Japan, this is estimated at 0.82 per 100,000 persons; the disease shows a male predilection. AIP is classified into two subtypes - type 1 and type 2; the former is believed to be the pancreatic manifestation of a multiorgan disease, with histology revealing a lymphoplasmacytic sclerosing pancreatitis (LPSP), and elevated immunoglobulin G4 (IgG4) levels being present. Type 2 AIP is a disease specific to the pancreas, is not associated with IgG4, and demonstrates a very different histological pattern, with neutrophilic infiltration; this is also termed idiopathic duct-centric pancreatitis (IDCP). Note also that recent studies have highlighted an increased risk of malignancy in patients with IgG4-related disease - particularly colon cancer, lung cancer and lymphoma; there may also be a slightly increased risk of pancreatic malignancy. Obstructive jaundice is the most common presentation of AIP; these patients may also present with acute pancreatitis, or complaining of recurrent or chronic abdominal pain. Note that severe pain is uncommon, as is significant weight loss. Extrapancreatic manifestations may also be present; these include Sjögren syndrome, lung nodules, interstitial nephritis, and retroperitoneal fibrosis. Histological studies are the traditional gold standard of diagnosis; endoscopic ultrasound (EUS) in conjunction with fine needle aspiration (FNA) or tru-cut biopsy is the least invasive technique in this regard. However, in clinical practice, most cases of AIP are first diagnosed by radiologists who recognize suggestive imaging findings on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) films. These include a 'sausage-like' appearance of the pancreas, which is due to the diffuse enlargement of the entire gland; and delayed enhancement and/or rim enhancement, due to pancreatic inflammation, edema, and fibrosis. Note that in certain patients, a focal swelling of the pancreas may be seen instead, mimicking a malignancy. While EUS may also reveal diffuse hypoechoic pancreatic enlargement, bile duct wall thickening and peripancreatic hypoechoic margins, these findings are not specific enough to establish the diagnosis. In addition, endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP) may reveal characteristic changes of the pancreatic duct and biliary tree - particularly long stricture formation without significant associated upstream duct dilatation. Antibody studies are also of diagnostic value; serum IgG4 levels >140 mg/dL have been shown to have a sensitivity of 76% and specificity of 93% for the diagnosis of AIP. Given the variety of investigations available, numerous diagnostic criteria have been formulated over the years; these include the Mayo clinic criteria (HISORt criteria), Japanese Pancreas Society criteria, and Korean criteria. At the time of writing, the International Consensus Diagnostic Criteria (ICDC) are the most recent, having been formulated in 2010. These make use five key features of AIP (imaging characteristics of the pancreatic parenchyma and duct, antibody studies, extrapancreatic organ involvement, pancreatic histology, and response to corticosteroids) to determine the subtype present, and classify the diagnosis as either 'probable' or 'definite'. AIP is highly sensitive to corticosteroid therapy, with most patients showing a response within the first 2 weeks, and the majority eventually achieving complete remission. Note that steroids should only be started once pancreatic malignancy has been ruled out; furthermore, failure of response should prompt consideration of an alternate etiology. In patients refractory to steroids, azathioprine, mycophenolate mofetil, cyclophosphamide and rituximab have all been tried, but there is limited data on their efficacy. Overall, AIP appears to have a good prognosis; long-term survival in patients with both type 1 and type 2 is similar to that of age and gender matched controls.


Take home messages

  1. AIP is a rare, chronic inflammatory disease affecting the pancreas; it can occur as part of a systemic fibroinflammatory syndrome.
  2. The International Consensus Diagnostic Criteria (ICDC) are the current international standard for the diagnosis of AIP.
  3. Corticosteroids are the mainstay of therapy, but should only be commenced once pancreatic malignancy has been excluded.

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