Diagnosis of Autoimmune Pancreatitis: The Mayo Clinic Experience

doi:10.1016/j.cgh.2006.05.017

Clinical Gastroenterology and Hepatology

Volume 4, Issue 8, August 2006, Pages 1010-1016

https://doi.org/10.1016/j.cgh.2006.05.017 Get rights and content

Background & Aims: The Japan Pancreas Society criteria for diagnosis of autoimmune pancreatitis (AIP) mandate presence of characteristic imaging (diffuse pancreatic enlargement with diffusely irregular, narrow pancreatic duct). AIP has unique histologic features associated with infiltration of tissues of affected organs with abundant IgG4-positive cells. We propose expanded diagnostic criteria for AIP with a cohort of histologically confirmed AIP. Methods: We reviewed the pancreatic imaging findings on computed tomography scans, serum IgG4 levels, other organ involvement, and response to steroids in 29 consecutive patients who met histologic criteria for AIP. Results: Computed tomography scans (n = 22) showed diffuse pancreatic enlargement in 6 (27%) patients; the rest had focal enlargement, distinct mass, normal pancreas, or focal acute pancreatitis. Serum IgG4 level was elevated in 15 of 21 (71%) patients, and other organ involvement (eg, intrahepatic biliary strictures) was noted in 11 of 29 (38%) patients. All 17 patients treated with steroids exhibited resolution/marked improvement of pancreatic/extrapancreatic manifestation. On the basis of this experience we propose that diagnosis of AIP can be made in patients with ≥1 of these criteria: (1) diagnostic histology, (2) characteristic imaging on computed tomography and pancreatography with elevated serum IgG4 level, or (3) response to steroid therapy of pancreatic/extrapancreatic manifestations of AIP. Twenty additional patients met expanded diagnostic criteria for AIP, and their demographic and clinical profile was similar to that of the 29 patients meeting histologic criteria. Conclusions: AIP defined by histological criteria shows a wide spectrum of radiologic features, with characteristic imaging seen only in a minority. Incorporation of additional features into current diagnostic criteria can identify the full spectrum of clinical presentations of AIP.

Section snippets

Methods

The study was approved by the Mayo Foundation Institutional Review Board.

Demographics and presentation

The mean age of the 29 patients was 63 ± 18 years (range, 14–85 years), with 23 (79%) being >50 years of age; majority (83%) were male. Presentation at the onset of symptoms was with obstructive jaundice in 23 (73%) patients, with pancreatic mass in 3, and with new-onset diabetes, steatorrhea, and pancreatitis in 1 each. Abdominal pain was present at onset in 10 of 29 (34.5%) patients but was mild in all, and none required narcotics for pain relief. At diagnosis, which was made weeks to years

Discussion

Unlike usual chronic pancreatitis, AIP is a relatively painless disease, despite histology showing chronic pancreatic inflammation and evidence of pancreatic edema, peripancreatic inflammation, and in some cases pancreatic calculi. Although the most common acute presentation of AIP is with obstructive jaundice, it has protean other manifestations, both pancreatic and extrapancreatic.1, 13, 25, 26, 27, 28, 29 Many patients present during the postacute phase, months to years after initial

References (33)

T. Kamisawa et al.
Treating patients with autoimmune pancreatitisresults from a long-term follow-up study
Pancreatology
(2005)
D. Yadav et al.
Idiopathic tumefactive chronic pancreatitisclinical profile, histology, and natural history after resection
Clin Gastroenterol Hepatol
(2003)
J. Kino-Ohsaki et al.
Serum antibodies to carbonic anhydrase I and II in patients with idiopathic chronic pancreatitis and Sjogren’s syndrome
Gastroenterology
(1996)
T. Kamisawa et al.
Autoimmune pancreatitis is a systemic autoimmune disease
Am J Gastroenterol
(2003)
A. Shinji et al.
Autoimmune pancreatitis is closely associated with gastric ulcer presenting with abundant IgG4-bearing plasma cell infiltration
Gastrointest Endosc
(2004)
T. Kamisawa
IgG4-positive plasma cells specifically infiltrate various organs in autoimmune pancreatitis
Pancreas
(2004)
R.K. Pearson et al.
Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist?
Pancreas
(2003)
K. Suda et al.
Histopathologic characteristics of autoimmune pancreatitis based on comparison with chronic pancreatitis
Pancreas
(2005)
G. Zamboni et al.
Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitisa study on 53 resection specimens and 9 biopsy specimens
Virchows Arch
(2004)
S.M. Weber et al.
Lymphoplasmacytic sclerosing pancreatitisinflammatory mimic of pancreatic carcinoma
J Gastrointest Surg
(2003)

G. Kloppel et al.

Autoimmune pancreatitispathological, clinical, and immunological features

Pancreas

(2003)

S.C. Abraham et al.

Pancreaticoduodenectomy (Whipple resections) in patients without malignancyare they all ‘chronic pancreatitis’?

Am J Surg Pathol

(2003)

K. Notohara et al.

Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltrationclinicopathologic features of 35 cases

Am J Surg Pathol

(2003)

T. Kamisawa et al.

A new clinicopathological entity of IgG4-related autoimmune disease

J Gastroenterol

(2003)

T. Kamisawa et al.

Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis

Gut

(2003)

T. Kamisawa et al.

Lymphoplasmacytic sclerosing pancreatitis is a pancreatic lesion of IgG4-related systemic disease

Am J Surg Pathol

(2004)

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We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP.
We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054–3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818–1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427–0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose.
Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.
IgG4-related cholangitis – a mimicker of fibrosing and malignant cholangiopathies
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IgG4-related cholangitis (IRC) is the major hepatobiliary manifestation of IgG4-related disease (IgG4-RD), a systemic fibroinflammatory disorder. The pathogenesis of IgG4-RD and IRC is currently viewed as multifactorial, as there is evidence of a genetic predisposition while environmental factors, such as blue-collar work, are major risk factors. Various autoantigens have been described in IgG4-RD, including annexin A11 and laminin 511-E8, proteins which may exert a partially protective function in cholangiocytes by enhancing secretion and barrier function, respectively. For the other recently described autoantigens, galectin-3 and prohibitin 1, a distinct role in cholangiocytes appears less apparent. In relation to these autoantigens, oligoclonal expansions of IgG4⁺ plasmablasts are present in patients with IRC and disappear upon successful treatment. More recently, specific T-cell subtypes including regulatory T cells, follicular T helper 2 cells, peripheral T helper cells and cytotoxic CD8⁺ and CD4⁺ SLAMF7⁺ T cells have been implicated in the pathogenesis of IgG4-RD. The clinical presentation of IRC often mimics other biliary diseases such as primary sclerosing cholangitis or cholangiocarcinoma, which may lead to inappropriate medical and potentially invalidating surgical interventions. As specific biomarkers are lacking, diagnosis is made according to the HISORt criteria comprising histopathology, imaging, serology, other organ manifestations and response to therapy. Treatment of IRC aims to prevent or alleviate organ damage and to improve symptoms and consists of (i) remission induction, (ii) remission maintenance and (iii) long-term management. Glucocorticosteroids are highly effective for remission induction, after which immunomodulators can be introduced for maintenance of remission as glucocorticosteroid-sparing alternatives. Increased insight into the pathogenesis of IRC will lead to improved diagnosis and novel therapeutic strategies in the future.
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Diagnosis and management of autoimmune pancreatitis during pregnancy. Autoimmune pancreatitis is a rare and life-threatening condition with increased maternal and fetal morbidity and mortality. Autoimmune pancreatitis may result in a mass-forming lesion in the pancreas resembling pancreatic cancer; therefore, meticulous and careful investigations must be done to avoid misdiagnosing autoimmune pancreatitis as pancreatic cancer. Since autoimmune pancreatitis improves dramatically to steroid therapy, accurate diagnosis of autoimmune pancreatitis can avoid unnecessary procedures, surgeries, and pancreatic resection. A case of a pregnant lady in her third trimester was presented with abdominal pain, nausea, and vomiting. On examination, there was tenderness in both epigastric and right hypochondrium associated with elevated serum amylase, liver transaminases, alkaline phosphatase, gamma-glutamyl transpeptidase, and immunoglobulin G4. Both abdominal ultrasound and magnetic resonance cholangiopancreatography showed a pancreatic head lesion with dilation in both pancreatic duct and common bile duct. Steroid was initiated that resulted in rapid and dramatic responsiveness. Acute pancreatitis is uncommon during pregnancy, and autoimmune pancreatitis is a very rare form of acute pancreatitis; therefore, a clear and rapid assessment, diagnosis, and management plan are necessary to avoid maternal and fetal morbidity and mortality.
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Proper assessment of disease activity and prediction of relapse are crucial for the management of autoimmune pancreatitis (AIP). The M-ANNHEIM-AiP-Activity-Score (MAAS) has been proposed to determine disease activity and predict relapse in German and Swedish patients with AIP. MAAS is calculated using six categories: pain report, pain control, exocrine insufficiency, endocrine insufficiency, imaging, and complications. This study aimed to clarify the usefulness of MAAS to predict relapse in Japanese patients with type 1 AIP.
We retrospectively analyzed 117 patients with type 1 AIP undergoing initial and maintenance steroid treatments at our institute between April 2006 and March 2021. AIP was diagnosed according to the Japanese Diagnostic Criteria for AIP 2018. We examined the association of MAAS with relapse during and after maintenance treatment.
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Original articleDiagnosis of Autoimmune Pancreatitis: The Mayo Clinic Experience

Section snippets

Methods

Demographics and presentation

Discussion

Pancreatology

Clin Gastroenterol Hepatol

Gastroenterology

Am J Gastroenterol

Gastrointest Endosc

IgG4-positive plasma cells specifically infiltrate various organs in autoimmune pancreatitis

Pancreas

Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist?

Pancreas

Histopathologic characteristics of autoimmune pancreatitis based on comparison with chronic pancreatitis

Pancreas

Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitisa study on 53 resection specimens and 9 biopsy specimens

Virchows Arch

Lymphoplasmacytic sclerosing pancreatitisinflammatory mimic of pancreatic carcinoma

J Gastrointest Surg

Autoimmune pancreatitispathological, clinical, and immunological features

Pancreas

Pancreaticoduodenectomy (Whipple resections) in patients without malignancyare they all ‘chronic pancreatitis’?

Am J Surg Pathol

Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltrationclinicopathologic features of 35 cases

Am J Surg Pathol

A new clinicopathological entity of IgG4-related autoimmune disease

J Gastroenterol

Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis

Gut

Lymphoplasmacytic sclerosing pancreatitis is a pancreatic lesion of IgG4-related systemic disease

Am J Surg Pathol

Original article
Diagnosis of Autoimmune Pancreatitis: The Mayo Clinic Experience