Teaching Case

A 60-year-old male, with no relevant history, presents at the Emergency Department (ED) with epigastralgia, jaundice and pruritus. Laboratory analysis revealed conjugated hyperbilirubinemia, hepatic cytolysis and mild hyperglycemia. Inpatient abdominal CT and MRI are presented, as well as an MRI study performed 5 years after hospital discharge.

Contrast-enhanced CT (Fig. 1) and MRI (Fig. 2), performed a few days after, demonstrated a diffusely enlarged and hypodense pancreas at unenhanced images, with delayed enhancement of the parenchyma and absence of its normal lobulation. At MRI, the pancreatic parenchyma was T1-hypointense, moderately T2-hyperintense and showed restriction on diffusion-weighted images. Additionally, a halo was seen surrounding the gland, with low attenuation at CT, hypointensity on T1-WI and T2-WI, and delayed enhancement. No parenchymatous focal lesions were seen and the main pancreatic duct was diffusely narrowed. There was no dilation of the bile ducts nor signs of cholelithiasis, and the gallbladder was physiologically distended. Nevertheless, the gallbladder and the extrahepatic bile ducts revealed diffuse wall enhancement.

The abdominal MRI performed 5 years later (Fig. 3) showed diffuse pancreatic atrophy. Furthermore, marked thickening of the renal pelvis was seen, with delayed enhancement and restricted diffusion.

The imaging findings suggested the diagnosis of Immunoglobulin G4-related disease (IgG4-RD), manifested by autoimmune pancreatitis (AIP) and sclerosing cholangitis (SC).  This hypothesis was confirmed by the elevated serum IgG4 (660,0 mg/dL) and histologic examination after endoscopic ultrasound-guided fine needle biopsy of the pancreas. The patient was treated with oral corticosteroids and antidiabetics, with successful remission of the disease. Recurrence of IgG4-RD was observed 5 years later, with renal involvement and serum IgG4 elevation.

IgG4-RD is a multiorgan immune-mediated fibroinflammatory condition, encompassing AIP, SC, retroperitoneal fibrosis, salivary gland and orbital disease. Previously thought as independent diseases, these manifestations were shown to share several features, namely organ enlargement due to lymphoplasmacytic infiltration by IgG4-positive plasma cells, obliterative phlebitis and fibrosis [1].

Biopsy is the diagnostic gold standard, with additional criteria including elevated serum IgG4 (≥135 mg/dL), characteristic morphological organ changes with multiorgan involvement, and response to corticosteroids [2].

There are no specific symptoms of AIP, with some patients presenting with mild abdominal pain, obstructive jaundice, weight loss and new onset of diabetes mellitus. [2,3]. AIP has two main morphological patterns. Diffuse AIP is the most common, manifested by a “sausage like” pancreas due to the gland’s enlargement and loss of lobulation. Focal AIP typically affects the pancreatic head, resulting in a mass-like appearance, making it more difficult to differentiate from pancreatic carcinoma [4,5,6].

The affected tissue is usually hypoechoic at US, hypoattenuating at unenhanced CT, mildly hyperintense at T2-WI, hypointense on T1-WI and shows delayed enhancement and restricted diffusion.  A specific finding is the presence of a capsule-like halo, probably corresponding to fibroinflammatory tissue, with low attenuation at CT, hypointense signal on T1-WI/T2-WI and delayed enhancement [2].

Obstructive jaundice is common, and it is usually associated with simultaneous SC. Intrahepatic and extrahepatic bile ducts can be affected, showing wall thickening, delayed enhancement and upstream dilatation. Gallbladder involvement occasionally occurs [7,8].

Renal involvement is seen in up to 35% of AIP patients and may present several patterns (generalized renal enlargement, focal parenchymal lesions or renal pelvic lesions), with the affected tissue having low signal on T1-W and T2-W images, with delayed enhancement [10,11].

Corticosteroids are the treatment’s mainstay and remission usually occurs within 4–6 weeks.  A burn-out phase is seen in 15% of patients after treatment, with pancreatic atrophy of the affected segments [9], as it was observed in our patient.

Written informed patient consent for publication has been obtained.

Take home points:

Autoimmune pancreatitis, cholangitis and kidney disease are part of the spectrum of IgG4-related disease.

The diagnosis of AIP is based on raised serum IgG4, clinical, radiological and histopathological findings.