Autoimmune pancreatitis can develop into chronic pancreatitis

Abstract

Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung's and Santorini's ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct.

Figure 1

CT findings in a 67-year-old woman with pancreatic head swelling. (A) CT at diagnosis in May 2005 showing pancreatic head swelling (arrows). (B), (C) CT 27 months later in August 2007 showing pancreatic stone formation and pancreatic atrophy (arrows). Data are reprinted from Ref. [41] with permission from the Journal of Gastroenterology.

Figure 2

ERCP and CT findings in a 69-year-old man with narrowing of both Wirsung’s and Santorini’s ducts. (A) ERCP at diagnosis in April 2001 showing Wirsung and Santorini duct narrowing (arrowheads). (B), (C) CT 105 months later in December 2009 showing pancreatic stone formation and pancreatic atrophy (arrow). Data are reprinted from Ref. [41] with permission from the Journal of Gastroenterology.

Figure 3

Images of AIP exhibiting definite chronic pancreatitis, and findings of AIP demonstrating independent risk factors for progression to chronic pancreatitis. (A) CT image of stones in pancreatic ducts (arrow). (B) CT image of multiple or numerous calcifications distributed throughout the entire pancreas (arrows). CT and ERCP findings of AIP demonstrating independent risk factors for progression to confirmed chronic pancreatitis at diagnosis. (C) CT finding of pancreatic head swelling at AIP diagnosis (arrows). (D) ERP finding of MPD non-narrowing in the pancreatic body at AIP diagnosis (arrowheads). (From Ref. [54]).

Figure 4

Progression rate for AIP to chronic pancreatitis. (A) Kaplan-Meier analysis of the progression rate to confirmed chronic pancreatitis in 73 patients with AIP. (B) Kaplan-Meier analysis of the progression rate to confirmed chronic pancreatitis in AIP based on the risk factors of pancreatic head swelling and MPD non-narrowing in the pancreatic body. Comparison of zero risk factor (n = 6), 1 risk factor (n = 45), and 2 risk factor (n = 21) groups. (From Ref. [54]). ^**P < 0.001 (log-rank test). CP: chronic pancreatitis.

Figure 5

Sequential progression mechanism of AIP to confirmed chronic pancreatitis. (A) Narrowing of both Wirsung’s and Santorini’s ducts (arrows) by pancreatic head swelling causes pancreatic juice stasis in the upstream pancreatic duct. (B) Pancreatic juice stasis results in increased intra-pancreatic duct pressure that is resistant to typical AIP-specific MPD narrowing in the pancreatic body region, leading to MPD non-narrowing in this region (arrowheads). (C) In concert with relapse, these events finally result in severe calcification. (From Ref. [54]).