Elsevier

Digestive and Liver Disease

Volume 43, Issue 9, September 2011, Pages 731-735
Digestive and Liver Disease

Liver, Pancreas and Biliary Tract
Characteristics of autoimmune pancreatitis based on serum IgG4 level

https://doi.org/10.1016/j.dld.2011.03.006Get rights and content

Abstract

Background

Autoimmune pancreatitis is categorized as an IgG4-related autoimmune disease, mostly associated with serological alterations, however characteristics of autoimmune pancreatitis based on serum markers have not been fully evaluated.

Methods

We evaluated demographics, symptoms, imaging and therapeutic outcome in 27 cases of autoimmune pancreatitis stratified by serum IgG4 level.

Results

Twenty patients (74%) had elevated serum IgG4 and 7 (26%) had normal IgG4 levels. Compared to patients with normal serum IgG4 levels, patients with elevated IgG4 had higher incidence of jaundice at onset (14.3% vs. 80%, respectively; P = 0.002), more frequent diffuse pancreatic enlargement at imaging (14.3% vs. 60%, respectively; P = 0.04), significantly higher 18F-2-fluoro-2-deoxy-d-glucose uptake of pancreatic lesions (SUV max: 4.0 vs. 5.7, respectively; P = 0.02), more frequent extrapancreatic lesions (42.9% vs. 85%, respectively; P = 0.03). Response to steroids was recognized regardless of serum IgG4 level, however maintenance therapy was required more frequently amongst patients with elevated compared to normal IgG4 (85.7% vs. 33.3%, respectively; P = 0.04).

Conclusions

Clinical features of autoimmune pancreatitis are different based on level of serum IgG4. Further studies are needed to clarify if normal serum IgG4 cases are a precursor of active type 1 or type 2 autoimmune pancreatitis.

Introduction

Autoimmune pancreatitis (AIP) is an IgG4-related systemic disease with various serological anomalies [1], and there is no global consensus in diagnostic criteria. Although diffuse or segmental narrowing of the main pancreatic duct and swelling of the pancreatic parenchyma are common criteria for diagnosing AIP, conditions including serum markers, histology, extrapancreatic lesions and steroid response are not consistent over the world [2], [3], [4]. A diverse set of serum markers is recommended in different countries: for example, γ-globulin, IgG, IgG4 and autoantibodies are used in Japan; IgG, IgG4 and autoantibodies in Korea; only IgG4 in U.S.A. The recently established international criteria were developed in Asia [2]. Although autoantibody was included in this criterion, γ-globulin was excluded. The sensitivity of γ-globulin (59.1%, cut-off value: 2.0 g/dl) was lower than IgG (72–73%) or IgG4 (80–95%) [5], [6] for diagnosing AIP. Autoantibody has been considered to be a serological marker of autoimmune association and reflects the activity of systemic inflammation in the course of steroid therapy [7]. The sensitivity of various antibodies ranged from 0% [antimitochondria antibody (AMA)] to 75% [antinuclear antibody (ANA) and antilactoferrin] [1], [6]. These serum markers have been selected mainly to differentially diagnose AIP and pancreatobiliary cancer [1], [4], [6].

Two different entities of AIP have been reported, i.e., type 1 AIP [lymphplasmacytic sclerosing pancreatitis (LPSP)] and type 2 AIP [idiopathic duct-centric pancreatitis (IDCP)] [8]. The reported incidences of these diseases vary from one country to the other [9]. Type 1 and type 2 are characterized by differences in age of onset, gender, histology, serum IgG4 level and other organ involvement [9]. Generally, type 2 AIP is less frequent than type 1 [8], especially in the Asian countries, and the response to steroids is unclear [9]. Hence, the differences in sets of serum markers adopted by different countries may reflect differences in serological backgrounds and demographics of AIP patients.

To date the clinical features of AIP stratified by serum markers has not been fully evaluated. We hereby report the different characteristics of AIP by serum IgG4 level.

Section snippets

Patients

Consecutive patients with AIP referred to Shizuoka Cancer Centre were recruited for the present study between April 2006 and May 2010. Patients were diagnosed according to the Asian criteria for AIP (2008) [2]. Both current and former smokers were included in the study. An intake >150 g per week was defined as positive alcohol use.

Clinical images

For the initial diagnosis of AIP, routine abdominal ultrasonography (US), multi-detector computed tomography (MDCT) and endoscopic retrograde cholangiopancreatography

Results

Of 27 patients enrolled, 25 were also diagnosed according to the Japanese criteria (2006) [1], but the remaining two cases were serologically negative and were diagnosed according to the optional condition of Asian criteria with response to steroid therapy [2]. Endoscopic ultrasonography-guided fine needle aspiration biopsy (EUS-FNAB) was performed in 26 cases using 22 gauge needle to exclude pancreatic malignancy. One case of definitive AIP was diagnosed without EUS-FNAB [10], and was negative

Discussion

In Asian countries, AIP occasionally lacks elevated serum IgG4 [17] and a small proportion of the cases are sero-negative [15], [18]. Generally, cases of active AIP with multiple systemic lesions tend to show high level of serum autoantibodies and/or IgG4 (Fig. 1) [7], [19], [20]. Although AIP with minute pancreatic lesions <1 cm in diameter has not been reported, it is possible that AIP at early onset would show minimal change in serological parameters. In the current study, many of the

Conflict of interest statement

None declared.

Acknowledgements

The authors are grateful to Miss. Mayumi Suhara and Miss. Satomi Koizumi for their helpful supports on patients’ care and endoscopic procedures.

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