DISCUSSION
IgG4-SC has been classified into four types based on the location of the
stenosis in the bile duct. Of them, type 1 (stenosis located at the
distal CBD) is mostly associated with AIP and presents with features of
obstructive jaundice, abdominal pain, weight loss, steatorrhea and
new-onset diabetes mellitus. 8-10 The IgG4-SC should
be distinguished from primary sclerosing cholangitis (PSC), pancreatitis
and cholangiocarcinoma which have similar manifestations. In AIP,
pancreatic imaging shows diffuse pancreatic enlargement and irregular
narrowing of the pancreatic duct. Similarly, serum CA 19-9 and CEA
levels can be used to rule out cholangiocarcinoma.10,
11 PSC is a progressive and chronic disease. It has a poor prognosis
and does not respond to steroid therapy.
AIP is the commonest systemic manifestation of the IgG4-SC. However, up
to 18% of the patients can have extra-pancreatic manifestations such as
sialadenitis, dacryocystitis, retroperitoneal fibrosis, and involvement
of lung, kidney and aorta.12 Very few cases of
exclusive IgG4-SC in the absence of the pancreatitis have been
reported.10 The case being presented here is one of
those.
An important biomarker frequently used in the diagnosis of the IgG4-RD
is serum IgG4 level. The exact mechanism of increased IgG4 levels in
IgG4-SC is not clear. It might directly mediate the inflammation or
could be produced by anti-inflammatory cytokines.13,
14 But, the definitive diagnosis of IgG4-SC is based on the HISORt
criteria (Histology, Imaging, Serology, Other organ involvement and
Response to therapy).9, 13
The histopathological (H) analysis of the resection specimen shows three
diagnostic hallmarks: lymphoplasmacytic infiltration, obliterative
phlebitis and storiform fibrosis.15 Cholangiogram or
computed tomography (CT) scan of the abdomen (I) is used to identify the
strictures at any point in the biliary tree.9, 16Serological study (S) is positive when the levels of IgG4 in serum are
elevated (>1.4 g/l). Involvement of other organs (O) and
response to steroid therapy (Rt), which shows the normalization of liver
enzymes or the resolution of stricture (radiologically), are the other
components of HISORt criteria.16 Either (H and Rt) or
(S and I) are required for the definitive diagnosis.17In our case, serum IgG4 level was increased (S), CT scan showed the
stricture in the distal CBD (I) and the patient responded to steroid
therapy (Rt), thus confirming the diagnosis of IgG4-SC.
The treatment of choice in IgG4-SC is a steroid, which has been proven
to induce quicker and consistent remission. Clinical recovery,
improvement in bile duct strictures in radiological study and
normalization in liver function tests are detected within weeks of
steroid therapy.16, 18 The patients need to be
monitored for relapse during the steroid therapy or thereafter, which is
treated with immunomodulatory drugs, in addition to the
steroid.16, 19 The three-year follow-up of the patient
being presented here showed remission on clinical, radiological and
biochemical grounds.
It is critical for physician to be aware of IgG4-SC without involvement
of pancreas as this condition can be easily misdiagnosed. Due to its
rarity and poor recognition, there have been cases where it was
erroneously treated as cholangiocarcinoma with surgical
resection.10, 20 Thus, IgG4-SC should also be
suspected in all cases of unexplained biliary strictures to prevent
unnecessary surgical interventions.