Autoimmune Pancreatitis with Multiorgan

Manu Nayar
, Richard Charnley
, John Scott
, Beate Haugk
, Kofi Oppong
Departments of
Hepatobiliary and Pancreatic Surgery,
Radiology, and
Cytopathology, Freeman Hospital. Newcastle Upon Tyne, United Kingdom
Context Autoimmune pancreatitis is increasingly being diagnosed as a multiorgan disorder and a small group of patient present a
diagnostic and management dilemma. Case report We report a complicated case of autoimmune pancreatitis with multiorgan
involvement. This is the first reported case of pericardial involvement and agrees with other authors that autoimmune pancreatitis is
a multisystem disorder predominantly affecting the pancreas. Conclusion In such cases more intensive immunosuppressive therapy
may be necessary to get better control of the disease as is apparent from this case.
Autoimmune pancreatitis is a disorder which
predominantly affects the pancreas. Over the past few
years this condition has been extensively studied and
there is an increasing consensus that autoimmune
pancreatitis is in fact a multisystem disorder
predominantly affecting the pancreas. Most patients
respond to steroids but occasionally additional
immunosuppression may be required.
We report a case of pericardial involvement in
autoimmune pancreatitis. The case is also complicated
by the fact that he did not respond to steroids and
required 6-mercaptopurine for control of his disease.
A sixty-year-old gentleman was admitted under the
surgical team with a two week history of abdominal
pain and dark urine in October 2001. There was no
history of jaundice, itching, weight loss or loss of
appetite. He suffered from left leg lymphedema,
Raynauds disease, transient ischemic attacks, ischemic
heart disease and had left sided hydronephrosis. He is a
chronic smoker but does not consume any alcohol. He
had lymph node biopsy performed in 1999. There was
no history of risk factors for liver disease. The positive
findings on examination were jaundice and
lymphedema of his left leg. The liver function tests
revealed a cholestatic pattern: total bilirubin 5.15
mg/dL (reference range: 0-1.11 mg/dL), alanine
transaminase 96 IU/L (reference range: 0-40 IU/L),
alkaline phosphatase 387 IU/L (reference range: 35-
120 IU/L) and gamma-glutamyl transpeptidase 278
IU/L (reference range: 0-50 IU/L). Transabdominal
ultrasound revealed generalised biliary dilatation. The
patient underwent an ERCP, which revealed a lower
common bile duct stricture. A plastic biliary stent was
inserted for drainage. The CA 19-9 was 126 U/mL
(reference range: 0-30 U/mL). The patient had a
computed tomography (CT) scan (Figure 1) performed,
which revealed a 3 cm mass in the head of the
Received December 18th, 2008 - Accepted July 14th, 2009
Key words
Immunoglobulin G; Pancreatic Neoplasms;
Pancreatitis, Chronic
Correspondence Manu Nayar
Freeman Hospital, High Heaton, Newcastle Upon Tyne, NE7 7DN
United Kingdom
Phone: +44-191.233.6161, ext 48755; Fax: +44-191.233.6266
Document URL
Figure 1. CT scan showing 3 cm mass (arrow) in the head of

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JOP. Journal of the Pancreas - - Vol. 10, No. 5 - September 2009. [ISSN 1590-8577]
pancreas. Radial endoscope ultrasound confirmed the
CT finding but also showed that the mass was encasing
the superior mesenteric veinIn view of these findings
a diagnosis of pancreatic cancer was considered. A
laparoscopy guided biopsy of the mass was performed
in March 2002 and this revealed diffuse replacement of
the pancreatic parenchyma by a fibrous stroma with
plasma cell infiltration and storiform fibrosis (Figure
2). The patient continued to be jaundiced and the
tumour marker CA 19-9 increased to 3,265 U/mL. The
decision was made to perform a palliative bypass
surgery for relief of symptoms. The operation
confirmed the CT and the EUS findings and therefore
the patient underwent a gastrojejunostomy,
choledochojejunostomy and a cholecystectomy in
2002. All the biopsies (pancreas, gallbladder, liver and
the lymph node) were reviewed by the specialist
histopathologist and a diagnosis of sclerosing
retroperitonitis was raised (Table 1). Meanwhile the
patient developed a nodular itchy rash during the
intervening period. The skin biopsies confirmed similar
findings. At this point his case was reviewed and a
diagnosis of autoimmune pancreatitis postulated. Total
immunoglobulin G (IgG) and subclass assay was
performed; results were as follows: IgG1, 17.84 g/L
(reference range: 2.2-10.4 g/L); IgG4: 9.48 g/L
(reference range: 2.0-2.4 g/L); IgG2 and IgG3 were
within the normal range. Previous pancreatic histology
was reviewed and was consistent with a diagnosis of
autoimmune pancreatitis.
The patient was started on prednisolone 40 mg od. He
responded very well to treatment but his symptoms
relapsed when the dose was tapered. He was restarted
on the same dose of prednisolone, i.e. 40 mg/day.
Repeat CT scan showed good resolution of the mass.
During this period he was admitted with signs of right
heart failure. He was on prednisolone 30 mg/day as the
treatment dose in this admission. The liver function
tests had worsened and the immunoglobulin G levels
were elevated .The echocardiogram was normal but a
magnetic resonance scan of the heart revealed
pericardial thickening (Figure 3). The patient
underwent a pericardectomy. Intraoperative findings
revealed a thickened pericardium and the surgeon
performed pericardial biopsies. The histopathology
findings revealed fibrous stroma and lymphocytes and
stained strongly for IgG4 (Figure 4). As he had
relapsed twice whilst on steroids we started him on
azathioprine. Unfortunately he did not respond/tolerate
azathioprine and he was started on 6-mercaptopurine.
Over a period of time the immunoglobulin levels and
liver function tests have gradually improved. His
steroid dose was tapered at the rate of 5 mg/week and
Table 1. Histological features at various stages of the disease.
Organs where the biopsies were performed
Lymph node
Fibrosis, chronic inflammatory cell infiltrate
Dense fibrous stroma, plasma cells and lymphocytes
Chronic inflammatory infiltrate
Lymphocytic vasculitis
Fibrous stroma and lymphocytes
Figure 2. Pancreatic core biopsy showing lymphoplasmacytic
sclerosing fibrosis (a.) and storiform fibrosis (b.).
Figure 3. MR scan showing pericardial thickening.

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JOP. Journal of the Pancreas - - Vol. 10, No. 5 - September 2009. [ISSN 1590-8577]
is now maintained on prednisolone 10 mg/day and 6-
mercaptopurine 75 mg/day.
Autoimmune pancreatitis has been described as a
primary pancreatic disorder and also in association
with other diseases of presumed autoimmune aetiology
including sclerosing cholangitis, primary biliary
cirrhosis, retroperitoneal fibrosis, rheumatoid arthritis,
sarcoidosis, and Sjögren’s syndrome [1]. The diagnosis
of autoimmune pancreatitis is based on a combination
of clinical, radiological, serological and histological
findings [2]. The mean age of presentation is in the
sixth decade with the age range between 30 to 80 years.
They classical present with a pancreatic mass in the
head of the pancreas [3] as in our patient. They may
also present with jaundice, abdominal pain, weight loss
and diabetes mellitus. In confirmed cases of
autoimmune pancreatitis effort should be made to look
for other systemic extra pancreatic manifestations of
the disease. Imaging is required to arrive at the
Immunology of Autoimmune Pancreatitis
Thought the exact cause of autoimmune pancreatitis is
uncertain immunological mechanisms play a vital role.
This theory is consolidated by many findings including
prevalence of hypergammaglobulinemia, auto
antibodies, specific immune mediated histological
changes and response to steroids. The immunoglobulin
subclass, IgG4, has found to be significantly raised in
this condition as compared to other autoimmune
disorders and a positive stain can be found in up to 85
% of the tissues [4]. The trigger for the IgG4 elevation
and its pathogenetic role in autoimmune pancreatitis
are unknown but one should interpret this with caution
as IgG4 can be elevated in certain malignancies. The
association of autoimmune pancreatitis with other
similar conditions, i.e. retroperitoneal fibrosis, has
resulted in the hypothesis that this could indeed be an
IgG4 related sclerosing process.
Though autoimmune pancreatitis should be considered
in all patients with a pancreatic mass it still remains a
rare disorder. The clinician should have a low threshold
for diagnosis as early treatment results in spontaneous
resolution of signs and symptoms.
As mentioned earlier when encountering a case of
autoimmune pancreatitis with elevated levels of
gammaglobulins, IgG, and IgG4, an effort should be
made to detect other systemic extrapancreatic
abnormalities. There is evidence that early
administration of steroid therapy is helpful in patients
with autoimmune pancreatitis and retroperitoneal
fibrosis. Our case is unusually complex as there are a
number of organs (i.e. pancreas, lymph node, liver,
gallbladder, retroperitoneum, skin and pericardium)
were involved at different times of the disease process.
Moreover, this is the second reported case of
pericardial involvement in autoimmune pancreatitis in
literature. Sugimoto et al. reported a case describing
constrictive pericarditis as an initial manifestation of
hyper-IgG4 disease [5].
The overall prognosis is said to be good as the disease
is self limiting in majority of the cases with or without
long term pancreatic dysfunction. There have been
numerous reports on dramatic response to steroids but
spontaneous response is also seen without treatment
[6]. Some patients may require low dose maintenance
There is very little data in the literature regarding use
of other immunosuppresives [7]. Response to steroids
in our patient was not sustained on discontinuation
necessitating the use of azathioprine and 6-
In conclusion, this case is unique because of the
involvement of a number of organs in a single
individual, i.e. lymph node, liver, pancreas, gall
bladder, skin and the pericardium. A selected group of
patients will have extensive multisystem disease that
may not respond to steroids and early
immunosuppression with alternative agents should be
considered. This case also reinforces the observations
by various authors that autoimmune pancreatitis is
probably an IgG4 related diffuse autoimmune disease.
Acknowledgement All the authors have been actively
involved in the management of the patient and the
preparation of the manuscript
Conflict of interest There are no conflicts of interests
to report
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Figure 4. Pericardial biopsy with a strongly positive IgG4 stain.

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