Some patients with autoimmune pancreatitis (AIP) form pancreatic stones suggestive of transformation into chronic pancreatitis (CP). The present study examined the underlying risk factors and mechanism of AIP progression to confirmed CP. We compared the clinical and laboratory parameters of subjects who progressed to confirmed CP with those of the subjucts who did not in a cohort of 73 type 1 AIP patients. A total of 16 (22%) AIP patients progressed to CP. Univariate analysis revealed that relapse was significantly more frequent in the progression group, and multivariate analysis indicated that pancreatic head swelling (OR 12.7, ) and nonnarrowing of the main pancreatic duct in the pancreatic body (OR 12.6, ) were significant independent risk factors for progression to CP. Kaplan-Meier testing showed that the progression rate to CP was approximately 10% at 3 years and 30% at 10 years in total AIP patients and 30% at 3 years and 60% at 10 years in subjects with both risk factors. AIP with pancreatic head swelling and a history of relapse may cause pancreatic juice stagnation and nonnarrowing of the main pancreatic duct in the pancreatic body, which can progress to advanced stage chronic pancreatitis. 1. Introduction Autoimmune pancreatitis (AIP) has been recognized as a distinctive type of pancreatitis possibly caused by autoimmune mechanisms [1–3]. Recently, AIP was classified into type 1 and type 2 based on the pathological differences, in which type 1 was designated as lymphoplasmacytic sclerosing pancreatitis (LPSP) and type 2 as idiopathic duct centric chronic pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL) [4–7]. Although the International Consensus Diagnostic Criteria (ICDC) [8] first enabled us to diagnose type 1 and type 2 AIP, AIP in Japan has revealed to be type 1 AIP exclusively. Along with this, all AIP patients in our institution have been diagnosed with type 1 by ICDC, and we have focused on the clinical study for type 1 AIP. Accordingly, in this paper, we dealt with type 1 AIP as AIP. AIP is characterized by pancreatic enlargement and irregular narrowing of the main pancreatic duct (MPD), both of which resemble the imaging features of pancreatic cancer [9, 10]. Other characteristic features of AIP include high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue, which are used in serological and pathological AIP diagnosis, respectively [11, 12]. As patients with AIP respond favorably to prednisolone (PSL) therapy, the disease was previously believed to be a nonprogressive condition that
References
[1]
K. Okazaki, K. Uchida, M. Koyabu, H. Miyoshi, and M. Takaoka, “Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease,” Journal of Gastroenterology, vol. 46, no. 3, pp. 277–288, 2011.
[2]
Y. Zen, D. P. Bogdanos, and S. Kawa, “Type 1 autoimmune pancreatitis,” Orphanet Journal of Rare Diseases, vol. 6, article 82, 2011.
[3]
T. Watanabe, K. Yamashita, S. Fujikawa, et al., “Involvement of activation of toll-like receptors and nucleotide-binding oligomerization domain-like receptors in enhanced IgG4 responses in autoimmune pancreatitis,” Arthritis and Rheumatism, vol. 64, pp. 914–924, 2012.
[4]
A. Sugumar, G. Kl？ppel, and S. T. Chari, “Autoimmune pancreatitis: pathologic subtypes and their implications for its diagnosis,” American Journal of Gastroenterology, vol. 104, no. 9, pp. 2308–2310, 2009.
[5]
K. Kawaguchi, M. Koike, K. Tsuruta, A. Okamoto, I. Tabata, and N. Fujita, “Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas,” Human Pathology, vol. 22, no. 4, pp. 387–395, 1991.
[6]
K. Notohara, L. J. Burgart, D. Yadav, S. Chari, and T. C. Smyrk, “Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltration: clinicopathologic features of 35 cases,” American Journal of Surgical Pathology, vol. 27, no. 8, pp. 1119–1127, 2003.
[7]
G. Zamboni, J. Lüttges, P. Capelli et al., “Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens,” Virchows Archiv, vol. 445, no. 6, pp. 552–563, 2004.
[8]
T. Shimosegawa, S. T. Chari, L. Frulloni et al., “International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the international association of pancreatology,” Pancreas, vol. 40, no. 3, pp. 352–358, 2011.
[9]
K. Yoshida, F. Toki, T. Takeuchi, S. I. Watanabe, K. Shiratori, and N. Hayashi, “Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis,” Digestive Diseases and Sciences, vol. 40, no. 7, pp. 1561–1568, 1995.
[10]
S. Kawa, H. Hamano, and K. Kiyosawa, “Pancreatitis,” in The Autoimmune Diseases, N. Rose and I. MacKay, Eds., Academic Press, St. Louis, Mo, USA, 4th edition, 2006.
[11]
H. Hamano, S. Kawa, A. Horiuchi et al., “High serum IgG4 concentrations in patients with sclerosing pancreatitis,” The New England Journal of Medicine, vol. 344, no. 10, pp. 732–738, 2001.
[12]
H. Hamano, S. Kawa, Y. Ochi et al., “Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis,” The Lancet, vol. 359, no. 9315, pp. 1403–1404, 2002.
[13]
M. Takayama, H. Hamano, Y. Ochi et al., “Recurrent attacks of autoimmune pancreatitis result in pancreatic stone formation,” American Journal of Gastroenterology, vol. 99, no. 5, pp. 932–937, 2004.
[14]
S. Kawa, H. Hamano, Y. Ozaki et al., “Long-term follow-up of autoimmune pancreatitis: characteristics of chronic disease and recurrence,” Clinical Gastroenterology and Hepatology, vol. 7, supplement 1, pp. S18–S22, 2009.
[15]
K. Takuma, T. Kamisawa, T. Tabata, et al., “Short-term and long-term outcomes of autoimmune pancreatitis,” European Journal of Gastroenterology & Hepatology, vol. 23, pp. 146–152, 2011.
[16]
K. Suzuki, S. Itoh, T. Nagasaka, H. Ogawa, T. Ota, and S. Naganawa, “CT findings in autoimmune pancreatitis: assessment using multiphase contrast-enhanced multisection CT,” Clinical Radiology, vol. 65, no. 9, pp. 735–743, 2010.
[17]
R. P. Sah, R. Pannala, S. T. Chari et al., “Prevalence, diagnosis, and profile of autoimmune pancreatitis presenting with features of acute or chronic pancreatitis,” Clinical Gastroenterology and Hepatology, vol. 8, no. 1, pp. 91–96, 2010.
[18]
H. Takada, T. Nakazawa, H. Ohara et al., “Role of osteopontin in calcification in autoimmune pancreatitis,” Digestive Diseases and Sciences, vol. 54, no. 4, pp. 793–801, 2009.
[19]
T. Nakazawa, H. Ohara, H. Sano et al., “Difficulty in diagnosing autoimmune pancreatitis by imaging findings,” Gastrointestinal Endoscopy, vol. 65, no. 1, pp. 99–108, 2007.
[20]
T. Nishino, F. Toki, H. Oyama, K. Shimizu, and K. Shiratori, “Long-term outcome of autoimmune pancreatitis after oral prednisolone therapy,” Internal Medicine, vol. 45, no. 8, pp. 497–501, 2006.
[21]
F. Maire, Y. Le Baleur, V. Rebours et al., “Outcome of patients with type 1 or 2 autoimmune pancreatitis,” American Journal of Gastroenterology, vol. 106, no. 1, pp. 151–156, 2011.
[22]
M. Maruyama, N. Arakura, Y. Ozaki, et al., “Risk factors for pancreatic stone formation in autoimmune pancreatitis over a long-term course,” Journal of Gastroenterology, vol. 47, pp. 553–560, 2012.
[23]
T. Shimosegawa, K. Kataoka, T. Kamisawa et al., “The revised Japanese clinical diagnostic criteria for chronic pancreatitis,” Journal of Gastroenterology, vol. 45, no. 6, pp. 584–591, 2010.
[24]
M. Otsuki, J. B. Chung, K. Okazaki et al., “Asian diagnostic criteria for autoimmune pancreatitis: consensus of the Japan-Korea Symposium on Autoimmune Pancreatitis,” Journal of Gastroenterology, vol. 43, no. 6, pp. 403–408, 2008.
[25]
J. R. Haaga, R. J. Alfidi, and M. G. Zelch, “Computed tomography of the pancreas,” Radiology, vol. 120, no. 3, pp. 589–595, 1976.
[26]
K. Okazaki, S. Kawa, T. Kamisawa, T. Shimosegawa, and M. Tanaka, “Japanese consensus guidelines for management of autoimmune pancreatitis: I. Concept and diagnosis of autoimmune pancreatitis,” Journal of Gastroenterology, vol. 45, no. 3, pp. 249–265, 2010.
[27]
K. Okazaki, S. Kawa, T. Kamisawa et al., “Japanese clinical guidelines for autoimmune pancreatitis,” Pancreas, vol. 38, no. 8, pp. 849–866, 2009.
[28]
I. Nishimori, A. Tamakoshi, S. Kawa et al., “Influence of steroid therapy on the course of diabetes mellitus in patients with autoimmune pancreatitis: findings from a nationwide survey in Japan,” Pancreas, vol. 32, no. 3, pp. 244–248, 2006.
[29]
S. Kawa and H. Hamano, “Clinical features of autoimmune pancreatitis,” Journal of Gastroenterology, vol. 42, supplement 18, pp. 9–14, 2007.
[30]
P. A. Hart, T. Kamisawa, W. R. Brugge, et al., “Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis,” Gut. In press.
[31]
K. Hirano, M. Tada, H. Isayama, et al., “High alcohol consumption increases the risk of pancreatic stone formation and pancreatic atrophy in autoimmune pancreatitis,” Pancreas, vol. 42, no. 3, pp. 502–505, 2012.
