ALL Metrics
-
Views
-
Downloads
Get PDF
Get XML
Cite
Export
Track
Case Report

Case Report: Painless obstructive jaundice caused by IgG4 autoimmune pancreatitis; the role of endoscopic ultrasound in diagnosis

[version 1; peer review: 2 not approved]
PUBLISHED 18 Nov 2020
Author details Author details
OPEN PEER REVIEW
REVIEWER STATUS

Abstract

We report the case of a 60-year-old woman, presenting with painless obstructive jaundice of unknown etiology, who was finally found to suffer from type I autoimmune pancreatitis (AIP). This case emphasizes AIP as a rare cause in the differential diagnosis of obstructive jaundice and the role of endoscopic ultrasound (EUS) in final diagnosis, which is difficult to establish. According to diagnostic criteria, we combined the results from serologic, imaging and histological features (specifically lgG4 levels, computed tomography, magnetic resonance imaging/magnetic resonance cholangiopancreatography and EUS) with cytological results, leading to a final diagnosis. Our patient’s response to corticosteroids was impressive, confirming the diagnosis, leading to complete remission of the disease. Whilst diagnosis of AIP is challenging, the application of diagnostic criteria can lead to correct diagnosis. Therapy is corticosteroid based, with very satisfying outcomes.

Keywords

autoimmune pancreatitis, obstructive jaundice, IgG4-related disease, endoscopic ultrasound, corticosteroids.

Introduction

Autoimmune pancreatitis (AIP) is a rare disease, meaning that clinicians have little experience in diagnosis1. Clinical suspicion is the first step for correct diagnosis, arising from the patient’s demographics and clinical presentation. This case presented here emphasizes the major role of endoscopic ultrasound (EUS) and biopsy in the final diagnosis of AIP, when other diagnostic procedures fail to offer an accurate answer.

Case description

A female patient, 60-years-old, was admitted to the emergency department with painless jaundice. The patient did not have any history of alcohol consumption, drug abuse, or previous liver and biliary or hematologic diseases.

Clinical findings

On clinical examination, the patient’s eyes and skin were yellow. Murphy and Giordano signs were negative. Blood tests showed serum lipase and amylase within normal limits, total bilirubin at 11.2mg/dl [normal range: 0.3–1.5mg/dL] (direct fraction 5.9 mg/dL, indirect fraction 5.3 mg/dL), hematocrit within normal limits, white blood cell count of 5.5 K/μL [normal range: 4.5–11 K/μL], and a normal fasting blood glucose level. Patient’s liver enzymes were elevated (aspartate aminotransferase 109 U/L [normal range 7–40U/L]; alkaline aminotransferase 230U/L [normal range: 5–45U/L]; alkaline phosphatase 238U/L [normal range: 40–150U/L]). Initial ultrasound examination revealed enlargement of the pancreas, with low echogenicity and dilatation of the biliary tree. The diameter of the pancreatic duct was normal (Figure 1).

cc91129b-ea3a-4b72-8fa4-cc6e677efde6_figure1.gif

Figure 1. Initial ultrasound showing diffuse pancreatic enlargement and common bile duct dilatation.

Anterioposterior diameter of pancreatic head was 48.9mm and body up to 23.6mm. Diameter of bile duct was 12.9mm.

Diagnostic assessment

Dynamic computed tomography revealed free peripancreatic fat with no other signs, indicating acute pancreatitis and mild enlargement of the pancreas with homogeneous density and enhancement. There were no signs indicating neoplasm.

For better evaluation of the pancreaticobiliary tree, an magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MPCP) was performed, showing mild pancreatic enlargement. There was no obvious dilatation of pancreatic duct, with stenosis of the final part of common bile duct (Figure 2).

cc91129b-ea3a-4b72-8fa4-cc6e677efde6_figure2.gif

Figure 2. MRI/MRCP showing mild pancreatic enlargement with normal pancreatic duct and narrowing of the final part of common bile duct.

Since MRCP has inferior resolution in the imaging of pancreatic duct, an endoscopic retrograde cholangiopancreatography (ERCP) was performed, which confirmed the MRCP findings, showing no significant prestenotic dilatation of the common bile duct. During the procedure, a dilatation of common bile duct with a balloon-catheter and a plastic stent placement was performed to alleviate the patient from jaundice. Furthermore, tissue-sampling was conducted from the stenosis, with results indicating inflammatory process of the duct wall. The patient was transferred to a tertiary centre, where, in order to obtain a more precise and direct imaging of the pancreas, EUS and EUS elastography was performed, showing a diffusely enlarged gland with hypoechoic, patchy, heterogeneous appearing parenchyma, with regions of stiffness, suggesting AIP. In addition, the presence of a hypoechoic mass in the final part of the intrapancreatic portion of common bile duct was found, which increased the suspicion of cholangiocarcinoma, deteriorating the diagnostic procedure (Figure 3). EUS with fine needle aspiration of the mass, using a 25-gauge needle, was performed. Several inflammatory cells, fibroblasts and traces of fibrous tissue were found in the samples. lgG4 levels were elevated, measuring 250mg/dl [normal range: <140mg/dL]. The combination of clinical, imaging and cytological findings pointed to the diagnosis of AIP.

cc91129b-ea3a-4b72-8fa4-cc6e677efde6_figure3.gif

Figure 3. Endoscopic ultrasound/elastography.

Hypoechoic mass in the distal part of intrapancreatic portion of common bile duct can be seen and diffusely enlarged gland with hypoechoic, patchy, heterogenous appearing parenchyma, with regions of stiffness.

Therapeutic intervention

Prednisolone 40mg daily for a month was given as therapy, leading to clinical and radiological disease remission. MRl one month following treatment revealed almost a normal pancreas (Figure 4), with subsequent normalization of lgG4 levels in serum. Nine months later, during dosage reduction with a taper of 5mg/week, the patient attended the emergency room once again, presenting with painless jaundice. Ultrasound indicated pancreas enlargement, with elevation of IgG4 in serum and [200mg/dL] the relapse of the disease. “Rebound phenomenon” was the most possible scenario. Re-induction/increased dose of steroid therapy to 40mg/daily for a two month period caused the remission of the disease. Α dose reduction rate of 5mg every 1–2 weeks followed, until prednisolone dose reached 15 mg/day. Then the reduction rate was decreased to 2.5mg every 2 weeks, until a dose of 3.0mg/day was reached.

cc91129b-ea3a-4b72-8fa4-cc6e677efde6_figure4.gif

Figure 4. Magnetic resonance imaging one month after treatment reveals almost normal pancreas.

Follow-up and outcomes

Maintenance therapy for three years was decided to prevent disease relapse, since most relapses occur in the first three years after diagnosis2. At the moment, three years later, the patient stays in remission, receiving 3.0mg/day of prednisolone.

Discussion

Autoimmune pancreatitis (AIP) consists of an uncommon type of chronic pancreatitis, accounting for 2–11% of all cases of chronic pancreatitis3. Two subtypes of the disease, defined by their histopathology, are clearly recognized since 20104: lymphoplasmacytic sclerosing pancreatitis, known as Type 1; and idiopathic duct-centric pancreatitis (ICDC), Type 2. Both types are steroid responsive. Type 1 is the pancreatic manifestation of lgG4-related disease. There are many extrapancreatic organs that may be involved, such as the biliary tree and gallbladder, kidneys, retro-peritoneum, prostate, the mesentery, blood vessels, gastrointestinal tract, thyroid, lacrimal glands and orbits, salivary glands, lymph nodes, and lungs5. The biliary tract is the most commonly involved extrapancreatic site, hence the painless jaundice in AIP patients, as in the present case5. The clinical features of AIP depend on the phase,acute or subacute. In the acute phase, the most common clinical presentation for both subtypes of AIP is obstructive jaundice, usually painless. In the subacute phase, AIP imitates chronic pancreatitis due to pancreatic atrophy, leading to steatorrhea. The incidence of diabetes mellitus in patients with AIP is up to 50%6. There are three established patterns of autoimmune pancreatitis depending on pancreatic appearance macroscopically: diffuse, as described in the current case, focal, and multifocal.

Diagnosis of AIP is challenging, and many clinical, imaging and biochemical features overlap with other conditions, such as idiopathic pancreatitis, primary sclerosing cholangitis and malignancies, mainly pancreatic cancer and cholangiocarcinoma. A plethora of diagnostic criteria have been proposed by different groups around the world. The first was proposed by the Japan Pancreas Society in 20027, combining cardinal features, concerning histology, imaging, serology, other organ involvement, and steroid effect3 (Table 1). ICDC is the first universally accepted criterion of AIP because it considers national differences and establishes two types8.

Table 1. Diagnostic criteria in different countries.

Japanese criteria
(2006)
HISORTs (2006)Korean criteria (2007)Asian criteria (2008)
A: ImagingDiffuse or segmental
narrowing of the MPD;
diffuse or localized
enlargement of the
pancreas
Typical imaging features:
diffusely enlarged gland with
delayed rim enhancement;
diffusely irregular and
attenuated MPD
Atypical imaging features:
focal pancreatic mass, focal
pancreatic duct stricture
Diffuse enlargement of
pancreas and diffuse
or segmental irregular
narrowing of MPD
Typical imaging features:
diffusely enlarged gland with
delayed rim enhancement,
diffusely irregular and
attenuated MPD
Atypical imaging features:
focal pancreatic mass, focal
pancreatic duct stricture
B: SerologyHigh serum γ globulin,
IgG, IgG4, or the
presence of antibodies
Elevated serum IgG4 levelElevated levels of IgG
and/or IgG4 or detected
autoantibodies
High level of IgG or IgG4 or
detected autoantibodies
C: HistologyInfiltration of
lymphocytes and plasma
cells
Lymphoplasmatic infiltrate
with storiform fibrosis showing
abundant (>10cells/HPF) IgG4-
positive cells
Fibrosis and
lymphoplasmatic
infiltration
Lymphoplasmatic infiltration
with fibrosis, with abundant
IgG4-positive cell infiltration
D: Other organ
involvement
Not includedBiliary stricture, parotid/
lacrimal gland involvement,
mediastinal lymphadenopathy,
retroperitoneal fibrosis
IncludedNot included
E: Steroid
effect
Not includedIncludedIncludedIncluded
Definitive
diagnosis
Criterion A + B
Criterion A + C
Criterion A + B
Criterion A + C
Criterion A + B
Criterion A + E
Criterion A + B
Criterion A + C
Criterion A + D
Criterion A + E
Criterion A + B
Criterion A + C
Histology shows the
presence of lymphoplasmatic
sclerosing pancreatities

MPD, main duct dilation; This table was adapted from Cai and Tan9 under a Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Exclusion of malignancy is crucial for the clinician to choose either conservative or surgical treatment. Focal pattern is most difficult to distinguish from cancer, especially ductal adenocarcinoma (PDAC)10, for which there is no pathognomonic biomarker, including lgG4 levels and CA 19-92,11. The mistaken diagnosis of AIP as PDAC, or vice versa, can result in unnecessary or life-threatening surgery or delayed treatment. Among diagnostic procedures (Table 2), EUS-FNA consists of a sensitive method for detecting/excluding pancreatic cancer, as in our case12.

Table 2. Advantages and disadvantages of imaging modalities.

ImagingImaging findingsAdvantageDisadvantageWhen to select
UltrasoundDiffuse enlargement,
hypoechoic pancreas
Low price,
noninvasive, easy to
operate.
Low specificity.Initial imaging.
Computed tomography (CT)Diffuse/focal pancreatic
enlargement, late
enhancement,
hypoattenuating halo
Non-invasive, easy to
operate, differentiate
AIP from pancreatic
cancer and other
pancreatitides.
Low sensitivity
in evaluation of
pancreatic and bile
duct.
Evaluate pancreatic
parenchyma, exclude
other pancreatitides/
cancer.
Magnetic resonance imagingHypointense signal on
T1 weighted images and
relatively T2 hyperintense
signal
Noninvasive showing
pancreatic fibrosis.
Less sensitivity
in pancreatic
parenchyma
evaluation than CT.
Evaluate pancreatic
parenchyma.
Magnetic resonance
cholangiopancreatography
Diffused narrow or
segmental stenosis of
main pancreatic duct,
the pancreatic segment
of common bile duct
stricture, proximal bile
duct dilatation, gallbladder
enlargement
Noninvasive, obtaining
high quality images of
the pancreatobiliary
tree.
Less sensitivity in
pancreatic/biliary
duct evaluation, no
treatment in case
of jaundice.
Evaluate the bile duct,
pancreatic duct and
bile duct stricture.
Endoscopic retrograde
cholangiopancreatography
Diffuse, irregular narrowing
of the main pancreatic duct
Better evaluate
pancreatic and biliary
duct, treatment
simultaneously,
especially in case of
jaundice.
Invasive.Evaluating bile and
pancreatic duct and
bile duct stricture,
treatment for
jaundice.
Endoscopic ultrasound-fine
needle aspirate
Diffusely enlarged gland
(“sausage-shaped”) with
hypoechoic, patchy,
heterogenous appearing
parenchyma.
Less invasive than
surgery in tissue-
sampling.
Invasive. May not
get adequate
tissue.
Get the pancreatic
tissue sample.
Positron emission
tomography
Uptake of
fluorodeoxyglucose in
organs other than the
pancreas.
Other organ
involvement is easily
detected.
ExpensiveEvaluate other organ
involvement, exclude
malignant tumor

This table was adapted from Cai and Tan9 under a Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The prognosis of AIP is generally good and complications rare. Our patient remains free from symptoms three years after diagnosis with a successful treatment of relapse. However, the role of AIP as a predisposing factor for pancreatic cancer needs to be investigated. Internists should keep in mind AIP as a rare entity in the diagnostic spectrum of pancreatic diseases and when high clinical suspicion exists, based on clinical presentation, demographics and patient’s history, should consider this diagnosis. Diagnosis can be made according to ICDC 20118. Clinicians, pathologists and radiologists have to be aware of this recently recognized entity13, to suspect and timely diagnose it, to give patient the appropriate steroid therapy, avoiding inappropriate pancreatic resections, which lead to increased morbidity and mortality.

Although diagnosis of AIP is challenging, respect to the established diagnostic criteria helps to have a definite and patient-safe result. When a clinical/radiological or other suspicion exists, clinicians should follow diagnostic algorithms to rule out other pathologies, especially pancreatic and billiard cancer. In our case, based on clinical presentation, the preferable diagnosis was malignancy, but imaging features of CT, ERCP and MRI/MRCP were not indicating this. EUS imaging deteriorated the diagnostic procedure, as it showed a hypoechoic mass, which is highly suspicious for malignancy, specifically cholangiocarcinoma. Finally, the combination of histological results, obtained after EUS biopsy, and elevated IgG4 levels established AIP diagnosis. In the current literature, the important role of EUS in the diagnosis of AIP has been highlighted. Our case emphasizes the role of EUS/elastography and EUS biopsy in diagnosis of the disease.

Exclusion of malignancy is crucial for the clinician to choose either conservative or surgical treatment. The misdiagnosis of AIP, especially focal pattern, as pancreatic duct adenocarcinoma, or the reverse, can result in medical malpractice. Sometimes biopsy is necessary, as in the present case and EUS is an ideal method for tissue sampling.

Glucocorticoids are the cornerstone in the therapeutic approach of AIP and effectiveness of steroid treatment consists of a major diagnostic criterion. Therapeutic goal of AIP is to achieve clinical, serologic and radiological remission of the disease.

Consent

Written informed consent for publication of clinical details and clinical images was obtained from the patient.

Data availability

All data underlying the results are available as part of the article and no additional source data are required.

Comments on this article Comments (0)

Version 1
VERSION 1 PUBLISHED 18 Nov 2020
Comment
Author details Author details
Competing interests
Grant information
Copyright
Download
 
Export To
metrics
Views Downloads
F1000Research - -
PubMed Central
Data from PMC are received and updated monthly.
- -
Citations
CITE
how to cite this article
Voidila S, Sideris P, Letsas C et al. Case Report: Painless obstructive jaundice caused by IgG4 autoimmune pancreatitis; the role of endoscopic ultrasound in diagnosis [version 1; peer review: 2 not approved]. F1000Research 2020, 9:1344 (https://doi.org/10.12688/f1000research.27017.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
track
receive updates on this article
Track an article to receive email alerts on any updates to this article.

Open Peer Review

Current Reviewer Status: ?
Key to Reviewer Statuses VIEW
ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 1
VERSION 1
PUBLISHED 18 Nov 2020
Views
8
Cite
Reviewer Report 23 Mar 2021
Zaheer Nabi, Asian Institute of Gastroenterology, Hyderabad, Telangana, India 
Not Approved
VIEWS 8
This is a case report entitled “Painless obstructive jaundice caused by IgG4 autoimmune pancreatitis; the role of endoscopic ultrasound in diagnosis”. The authors reported a classic case of autoimmune pancreatitis (AIP) presenting as obstructive jaundice. I have the following comments ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Nabi Z. Reviewer Report For: Case Report: Painless obstructive jaundice caused by IgG4 autoimmune pancreatitis; the role of endoscopic ultrasound in diagnosis [version 1; peer review: 2 not approved]. F1000Research 2020, 9:1344 (https://doi.org/10.5256/f1000research.29841.r80533)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Views
14
Cite
Reviewer Report 08 Mar 2021
Shin Miura, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan 
Not Approved
VIEWS 14
This paper is a case report of autoimmune pancreatitis (AIP). AIP is a disease for which diagnostic criteria have been established and is a common disease for specialists in our area. Many papers on autoimmune pancreatitis have already been reported. ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Miura S. Reviewer Report For: Case Report: Painless obstructive jaundice caused by IgG4 autoimmune pancreatitis; the role of endoscopic ultrasound in diagnosis [version 1; peer review: 2 not approved]. F1000Research 2020, 9:1344 (https://doi.org/10.5256/f1000research.29841.r80531)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.

Comments on this article Comments (0)

Version 1
VERSION 1 PUBLISHED 18 Nov 2020
Comment
Alongside their report, reviewers assign a status to the article:
Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
Sign In
If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password.

The email address should be the one you originally registered with F1000.

Email address not valid, please try again

You registered with F1000 via Google, so we cannot reset your password.

To sign in, please click here.

If you still need help with your Google account password, please click here.

You registered with F1000 via Facebook, so we cannot reset your password.

To sign in, please click here.

If you still need help with your Facebook account password, please click here.

Code not correct, please try again
Email us for further assistance.
Server error, please try again.