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.