IgG4 POSITIVE SCLEROSING CHOLANGITIS FOLLOWING AUTOIMMUNE PANCREATITIS

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IgG4 POSITIVE SCLEROSING CHOLANGITIS FOLLOWING
AUTOIMMUNE PANCREATITIS
Ong SL, Garcea G, Puls F, Richards CJ, Mulcahy K,
Grant A, Dennison AR, Berry DP
Department of Hepatobiliary and Pancreatic
Surgery, The Leicester General Hospital,
Leicester, UK
BACKGROUND
Figure 1 MRI scan shows beading appearances of
the intra-hepatic bile ducts
Table 1 Liver functions and CA19.9 level over
time with marked improvement observed following
steroid therapy
Autoimmune pancreatitis (AIP), also known as
sclerosing pancreatitis or lymphoplasmacytic
sclerosing pancreatitis, was first described by
Sarles et al in 1961. It is a unique form of
pancreatitis that accounts for up to 2 of
patients who undergo surgery for a potentially
malignant pancreatic mass. It is associated
with raised serum immunoglobulins, in particular,
elevated IgG4 levels and the presence of a number
of auto-antibodies. The inflammatory process may
involve the biliary tree at intra-hepatic and/or
extra-hepatic levels, leading to sclerosis and
stricture formation, with characteristic
lymphocytic infiltration within the biliary
epithelium. Primary sclerosing cholangitis
(PSC) is the commonest type of autoimmune
cholangitis encountered clinically. However,
similar pathology may occur in conjunction with
AIP, known as AIP-related sclerosing cholangitis.
Unlike PSC, this subtype shows good response to
steroid treatment. Hence, early recognition of
this unique disease entity is essential in order
to commence prompt steroid treatment, avoiding
unnecessary invasive investigations and
interventions, and expediting patient recovery.
Biliary Bypass
Steroid Introduced
Figure 2 Liver biopsy
Marked cholestasis of the hepatic parenchyma
highlighted by intra-cellular and
intra-canalicular bile plugs.
A lymphocytic infiltrate of the portal tracts
with intraepithelial location of lymphocytes is
seen. There is concentric deposition of collagen
around biliary tracts.
Verhoeff van Gieson (EVG) stain highlights the
collagen located in the biliary tracts. The
concentric orientation of fibres around the bile
duct is characteristic for a sclerosing
cholangitis.
CASE REPORT
A 72-year-old gentleman, who had previously
undergone a biliary bypass for AIP-induced
chronic pancreatitis, presented 4 months
following his surgery with symptoms suggestive of
obstructive jaundice and weight loss. The
simultaneous grossly elevated tumour marker,
CA19.9, raised the concern for underlying
malignancy (Table 1). An MRCP was performed,
showing prominent bile ducts throughout the liver
with a beaded appearance, suggesting the
possibility of sclerosing cholangitis (Figure 1).
The patients serum caeruloplasmin and
a1-antitrypsin level were normal and the
hepatitis screen and serum analysis for
auto-antibodies were negative. However, serum IgG
level was elevated at 19.4g/L and within the
sub-classification for serum IgG, the IgG4 level
was markedly raised at 2.94g/L. There was no
monoclonal band detected on serum
electrophoresis. A liver biopsy was taken and
the histological findings were in keeping with
AIP-associated sclerosing cholangitis (Figure 2).
The patient was commenced on oral steroid
treatment leading to a significant improvement to
the jaundice and a concurrent decline of the
CA19.9 level (Table 1).
DISCUSSION

• Steroids in the management of AIP and associated
  sclerosing cholangitis
• Disease remission achieved with 20mg to 40mg of
  oral steroid daily.
• No consensus on an optimal treatment regime.
• Role of long-term steroid to be defined.

AIP and associated sclerosing cholangitis are
often difficult to diagnose due to concern about
underlying malignancy. Cholestasis and spurious
elevation of tumour markers such as CA19.9
reinforce this differential diagnosis. As a
result, patients have frequently been subjected
to surgical exploration. Approximately 25 of
these patients have been reported to develop
recurrent jaundice after biliary bypass surgery.
CONCLUSIONS
AIP-associated sclerosing cholangitis is a
recognised disease entity. However, the
diagnosis is often difficult to reach and
frequently superseded by concerns of underlying
malignancy of the pancreatic and biliary tree.
The presence of elevated tumour markers must be
interpreted in collaboration with radiological
findings as well as serum immunoglobulin level,
in particular, IgG4 level. Early trials with
steroid treatment may prevent patients from
unnecessary surgical or endoscopic procedure to
relieve their jaundice. However, surgical
exploration and decompression of the biliary
system must be considered where the diagnosis is
uncertain and underlying malignancy cannot be
excluded.

• Radiological findings for AIP and associated
  sclerosing cholangitis
• CT or MRI are the commonest imaging modality
  used.
• Focal/diffuse enlargement of the pancreas.
• Diffuse irregular narrowing of the biliary and
• pancreatic ducts.
• Resolution of radiological appearance with
• disease remission.
• Common features of previously reported cases of
  AIP-associated sclerosing cholangitis are
• Presence of elevated serum IgG4 level.
• Lymphocytic and plasmacytic infiltration on
  histology.
• Difficulty in excluding a head of pancreas
  malignancy.
• Good response to steroid therapy.