Gut and Liver 2019; 13(4): 385-387 https://doi.org/10.5009/gnl19175 Differentiation of Type 2 Autoimmune Pancreatitis Presenting as Clinical Acute Pancreatitis
Author Information
Tae Hoon Lee
Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University School of Medicine, Cheonan, Korea

Tae Hoon Lee
Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University School of Medicine, 31 Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Korea
Tel: +82-41-570-3662, Fax: +82-41-574-5762, E-mail: thlee9@schmc.ac.kr
© The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Body

Autoimmune pancreatitis (AIP) is known to be a chronic fibrosis-inflammatory disease of the pancreas that responds to steroids. In 1995, Yoshida et al.1 introduced the term AIP to describe an inflammatory pancreatic disease reminiscent of autoimmune hepatitis. Since the establishment of diagnostic criteria for AIP in Japan in 2002, the concept of AIP has been increasingly recognized and nationwide diagnostic criteria have been proposed. Also, in South Korea, since the introduction of the diagnostic criteria of Kim et al.2 in 2006, concern over AIP has increased.

The diagnosis of AIP requires pancreatic parenchymal and ductal imaging, determination of the serum immunoglobulin G4 (IgG4) level, the presence of characteristic pathologic findings, and a response to steroid therapy. The serum IgG4 level is characteristically elevated in type 1 AIP (~66%) but this is not a confirmative diagnostic marker because the serum IgG4 level is elevated in <25% of patients with type 2 AIP.3 Based on an enhanced understanding of its clinical characteristics, AIP is divided into histological type 1 (lymphoplasmacytic sclerosing pancreatitis, LPSP) and type 2 (idiopathic duct-centric pancreatitis, IDCP). LPSP and IDCP share histopathologic and clinical features, and the term AIP came to be used for both diseases; LPSP was termed type 1 AIP and IDCP, type 2 AIP.4

However, definitive diagnosis of type 2 AIP is still difficult because the imaging findings of the pancreatic parenchyma and the steroid response are similar to those of type 1 AIP; therefore, a pathologic diagnosis is required for confirmation. The guidelines of the International Association of Pancreatology (IAP) provide level 1 and 2 diagnostic criteria for type 2 AIP (Table 1).5 A histologic evaluation of the pancreas is also important for diagnosis of type 2 AIP. In patients presenting with obstructive jaundice and/or diffuse pancreatic enlargement/mass, if serology does not indicate type 1 AIP and there is no involvement of other organs, type 2 AIP can be diagnosed by IDCP and the diagnosis confirmed by pancreatic biopsy after exclusion of malignancy. Therefore, until pathologic confirmation of IDCP, use of the term AIP can result in confusion. On this basis, it was recently proposed that the term “AIP” be used only for LPSP (currently type 1 AIP), and “IDCP” only for IDCP (currently type 2 AIP). However, the term “type 2 AIP” is more familiar to physicians.

Over the past decade, type 1 AIP has been investigated extensively in South Korea, but type 2 AIP may be mislabeled as AIP (without subtype specification). Type 2 AIP predominates in Western countries, and has a younger age of onset and no gender deviation.6 Also, in 16% to 30% of cases, type 2 AIP presents together with an inflammatory bowel disease (IBD) such as ulcerative colitis (UC).7,8

Although Oh et al.9 of Gut and Liver is a retrospective single-center study, results showed that the prevalence of type 2 AIP was not low in Korea. In that study, based on clinical, radiologic, and histologic evaluations the subjects were classified as “definite” or “probable” type 2 AIP according to the International Consensus Diagnostic Criteria. Among the 244 patients with AIP, 11.1% had type 2 AIP. All patients who received steroids but not surgical resection showed complete clinical and radiological remission.9 Endoscopic retrograde cholangiopan-creatography and pathologic analysis can provide confirmative information, but the risk of adverse events may preclude further examination of patients with idiopathic pancreatitis, particularly young patients. For this reason, they compared the image findings of computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP). In younger patients with idiopathic pancreatitis, and particularly in cases of a first attack, obtaining a biopsy for diagnostic purposes is associated with a risk of complications.

Clinically, type 1 AIP typically presents as painless obstructive jaundice, and type 2 AIP as acute pancreatitis in ~50% of patients. Therefore, type 2 AIP can be mistakenly classified as idiopathic pancreatitis. Therefore, a histologic evaluation of the pancreas is needed for a definitive diagnosis of type 2 AIP presenting as acute pancreatitis, as its clinical diagnosis is problematic. To diagnose type 2 AIP, attention should be paid to a specific patient subpopulation (e.g., IBD). Type 2 AIP reportedly develops in younger patients (median, 29 years; 70.6% males) and all patients with type 2 AIP require analgesics for pain control. Before their diagnosis with type 2 AIP presenting as acute pancreatitis, nine patients (52.9%) had a medical history of idiopathic acute pancreatitis, and all of them had clinically mild pancreatitis. Also, the frequency of UC as a co morbidity was higher than type 1 (n=8, 47.1%).9

CT and MRCP can provide meaningful diagnostic information for type 2 AIP. Compared with gallstone pancreatitis, CT findings of multifocal lesions, focal mass, capsule-like low-density rim, delayed enhancement, and focal or segmental main pancreatic duct dilatation are more common in cases of type 2 AIP. Indeed, multifocality (35.3% vs 0%, p<0.01), peripancreatic halo (11.8% vs 0%, p=0.01), and delayed enhancement (81.3% vs 0%, p<0.01) are found only in patients with type 2 AIP.9 However, patients with type 1 AIP may have similar features and it might be argued to compare with gallstone pancreatitis which also has its’ characteristics determined by image studies. Therefore, AIP should be diagnosed by stepwise exclusion of other types of pancreatitis and needs pathological diagnosis in type 2 AIP for differentiation.

In conclusion, type 2 AIP is not rare in South Korea and should be suspected in young UC patients who present with clinical acute pancreatitis of unknown etiology. Also, larger nationwide studies involving pathologic findings are required to improve the diagnosis of AIP.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

ACKNOWLEDGEMENTS

This work was supported by the Soonchunhyang University Research Fund.

Tables

International Association of Pancreatology Criteria for Type 2 Autoimmune Pancreatitis5

CriterionLevel 1Level 2
Parenchymal imagingTypical: diffuse enlargement with delayed enhancement (sometimes associated with rim-like enhancement)Indeterminate (including atypical): segmental/focal enlargement with delayed enhancement
Parenchymal imagingLong (>1/3 length of the main pancreatic duct) or multiple strictures without marked upstream dilatationSegmental/focal narrowing without marked upstream dilatation (duct size, <5 mm)
Other organ involvementClinically diagnosed inflammatory bowel disease
Histology of the pancreas (core biopsy/resection)IDCP, both of the following:Both of the following:
(1) Granulocytic infiltration of duct wall (GEL) with or without granulocytic acinar inflammation(1) Granulocytic and lymphoplasmacytic acinar infiltrate
(2) Absent or scant (0–10 cells/HPF) IgG4-positive cells(2) Absent or scant (0–10 cells/HPF) IgG4-positive cells
Response to steroidDiagnostic steroid trial
Rapid (≤2 weeks) radiologically demonstrable resolution or marked improvement in manifestations

IDCP, idiopathic duct-centric pancreatitis; HPF, high-power field; IgG4, immunoglobulin G4.

References
  1. Yoshida K, Toki F, Takeuchi T, Watanabe S, Shiratori K, Hayashi N. Chronic pancreatitis caused by an autoimmune abnormality: proposal of the concept of autoimmune pancreatitis. Dig Dis Sci 1995;40:1561-1568.
    Pubmed CrossRef
  2. Kim KP, Kim MH, Kim JC, Lee SS, Seo DW, Lee SK. Diagnostic criteria for autoimmune chronic pancreatitis revisited. World J Gastroenterol 2006;12:2487-2496.
    Pubmed KoreaMed CrossRef
  3. Hart PA, Krishna SG, Okazaki K. Diagnosis and management of autoimmune pancreatitis. Curr Treat Options Gastroenterol 2017;15:538-547.
    Pubmed CrossRef
  4. Zhang L, Chari S, Smyrk TC, et al. Autoimmune pancreatitis (AIP) type 1 and type 2: an international consensus study on histopathologic diagnostic criteria. Pancreas 2011;40:1172-1179.
    Pubmed CrossRef
  5. Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas 2011;40:352-358.
    Pubmed CrossRef
  6. Petzold G, Ellenrieder V, Neesse A. Autoimmune pancreatitis in Germany: rare but relevant. Digestion 2017;96:185-186.
    Pubmed CrossRef
  7. Kamisawa T, Chari ST, Giday SA, et al. Clinical profile of autoimmune pancreatitis and its histological subtypes: an international multicenter survey. Pancreas 2011;40:809-814.
    Pubmed CrossRef
  8. Sah RP, Chari ST, Pannala R, et al. Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis. Gastroenterology 2010;139:140-148.
    Pubmed CrossRef
  9. Oh D, Song TJ, Moon SH, et al. Type 2 autoimmune pancreatitis (idiopathic duct-centric pancreatitis) highlighting patients presenting as clinical acute pancreatitis: a single-center experience. Gut Liver 2019;13:461-470.
    Pubmed CrossRef
Tables

International Association of Pancreatology Criteria for Type 2 Autoimmune Pancreatitis5

CriterionLevel 1Level 2
Parenchymal imagingTypical: diffuse enlargement with delayed enhancement (sometimes associated with rim-like enhancement)Indeterminate (including atypical): segmental/focal enlargement with delayed enhancement
Parenchymal imagingLong (>1/3 length of the main pancreatic duct) or multiple strictures without marked upstream dilatationSegmental/focal narrowing without marked upstream dilatation (duct size, <5 mm)
Other organ involvementClinically diagnosed inflammatory bowel disease
Histology of the pancreas (core biopsy/resection)IDCP, both of the following:Both of the following:
(1) Granulocytic infiltration of duct wall (GEL) with or without granulocytic acinar inflammation(1) Granulocytic and lymphoplasmacytic acinar infiltrate
(2) Absent or scant (0–10 cells/HPF) IgG4-positive cells(2) Absent or scant (0–10 cells/HPF) IgG4-positive cells
Response to steroidDiagnostic steroid trial
Rapid (≤2 weeks) radiologically demonstrable resolution or marked improvement in manifestations

IDCP, idiopathic duct-centric pancreatitis; HPF, high-power field; IgG4, immunoglobulin G4.

Search for
Article
Archives