Chronic Pancreatitis, Pancreatic Cysts, and Pancreatic Neoplasms: Chronic Pancreatitis and Cysts: Autoimmune Types

0:00Welcome to Board Pearls. This is episode three of five of the Chronic Pancreatitis, Pancreatic Cysts, and Pancreatic Neoplasms chapter, in the Pancreatic and Biliary Disease module. This episode is autoimmune pancreatitis, the autoimmune cause in the TIGAR-O system, which imitates cancer and melts away with steroids. The first patient is an older man with painless jaundice, and his case shows what type one looks like and which clues outside the pancreas give it away, why an immunoglobulin G4, IgG4, level can't settle it, how the HISORt and international consensus criteria protect a patient from having a cancer treated with steroids, how much prednisone to give and for how long, what no response means, and who relapses and what keeps them in remission. The second patient is a younger woman with ulcerative colitis, and her case shows type two, a different disease with a different course.

0:53Here's the patient. A sixty-seven-year-old man has noticed yellow eyes and dark urine for two weeks. He has no abdominal pain. He's lost two kilograms. Both of his submandibular glands are swollen and firm. His bilirubin is six, and his alkaline phosphatase is four times normal. His computed tomography, CT, shows a diffusely enlarged, sausage-shaped pancreas with a thin, low-density rim around it, and a narrowed distal bile duct. His serum IgG4 is two and a half times the upper limit of normal.

1:25Painless jaundice, a sausage-shaped pancreas with a rim, swollen salivary glands, and a high IgG4 point to type one autoimmune pancreatitis, not the cancer his age and jaundice suggest. Autoimmune pancreatitis is the autoimmune category of TIGAR-O, and it matters most because it mimics pancreatic cancer and responds to steroids. An older man with painless jaundice and weight loss is the textbook picture of adenocarcinoma, which is exactly why this diagnosis has to be made carefully.

1:57His picture matches type one closely. Type one is lymphoplasmacytic sclerosing pancreatitis, the pancreatic form of IgG4-related disease. It typically affects people aged sixty to seventy, with men outnumbering women three to one, and it most often presents with painless obstructive jaundice. Severe pain usually points to another diagnosis, because IgG4-driven fibroinflammation compresses rather than destroys tissue. Imaging shows a diffusely enlarged, sausage-shaped gland, with a low-density, capsule-like rim in about thirty percent, or a focal mass that mimics adenocarcinoma. On endoscopic retrograde cholangiopancreatography, ERCP, the pancreatic duct is irregular and not dilated, without the double-duct sign of adenocarcinoma, in which both the pancreatic and bile ducts dilate upstream of a single point in the head. He fits type one on almost every feature.

2:54His salivary glands are part of the diagnosis, because type one is a systemic disease. Involvement of other organs is the diagnostic clue: IgG4-associated cholangitis, orbital pseudotumor, salivary gland enlargement, retroperitoneal fibrosis, periaortitis, kidney infiltrates, and lymphadenopathy. Its absence doesn't exclude the diagnosis, but its presence is highly supportive. His salivary glands are swollen, and his narrowed distal bile duct could be IgG4-associated cholangitis rather than a tumor in the head.

3:29His IgG4 supports the diagnosis but can't settle it. Serum IgG4 is raised in sixty to seventy percent of patients with type one, but a mild elevation, less than twice normal, occurs in up to about ten percent of patients with pancreatic adenocarcinoma, so a single raised value doesn't establish the diagnosis. His level of two and a half times normal, with other organs involved and classic imaging, supports it as one of several elements. A patient with a focal head mass, no sausage shape, no rim, no other organ involvement, and an IgG4 one and a half times normal fits cancer just as well, and that patient gets tissue and the criteria, not steroids on the strength of the IgG4.

4:12Formal criteria protect him from steroids given for a cancer. The HISORt criteria are histology, imaging, serology, other organ involvement, and response to steroids, and the international consensus diagnostic criteria weigh the same five elements slightly differently. They're strict because both diseases can cause a focal mass and obstructive jaundice, and steroids given to an undiagnosed cancer would delay resection and worsen its outcome. He has classic imaging, a high IgG4, and other organ involvement, and his biopsy shows a dense lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and more than ten IgG4-positive plasma cells per high-power field.

4:57His histology also separates the two types. Type one shows prominent storiform fibrosis, which is whorled collagen with an embedded infiltrate of lymphocytes and plasma cells; obliterative phlebitis, the infiltrate destroying vein walls; more than ten IgG4-positive plasma cells per high-power field; and no granulocytic epithelial lesion. Type two is the reverse: less storiform fibrosis, rare phlebitis, fewer than ten IgG4-positive cells, and the granulocytic epithelial lesion, neutrophils infiltrating the duct epithelium, which is its histologic hallmark. His biopsy confirms type one.

5:36With cancer excluded, he starts steroids promptly, because the inflammation won't stay reversible. Both types respond to prednisone, forty milligrams a day for four weeks, followed by a taper of five milligrams a week, without routine maintenance. Steroids suppress the fibroinflammatory infiltrate, which is reversible early but progresses to fixed fibrosis if it's left untreated. A clinical and biochemical response within two weeks is part of the diagnostic criteria, and failure to respond prompts re-evaluation for adenocarcinoma rather than more steroids. At two weeks his bilirubin has fallen from six to two, and his imaging is improving.

6:14His response doesn't mean cure, because his disease is chronic. Type one relapses in about thirty to fifty percent, because IgG4-related disease is a chronic, systemic plasma-cell disorder that one treated flare doesn't remove. Rituximab, an anti-CD20 antibody that depletes the B-cell precursors of plasma cells, is the steroid-sparing agent of choice for relapsing or steroid-intolerant type one disease. For a relapse treated with steroids alone, the alternative is prednisone plus azathioprine, six-mercaptopurine, or mycophenolate, overlapping with prednisone for at least eight weeks during the taper, so the immunomodulator is working before the steroid is withdrawn.

6:56His relapse follows that pattern. Eight months after his taper, his jaundice returns and his IgG4 rises. He's treated with prednisone for the flare and rituximab to keep him in remission. Had he tolerated steroids badly, he'd have moved to rituximab directly.

7:13The second patient shows that type two is a different disease. A forty-four-year-old woman with ulcerative colitis has had three attacks of acute pancreatitis in two years, with a focal enlargement of her pancreatic tail, a normal serum IgG4, and no other organ involvement. She most likely has type two autoimmune pancreatitis, also called idiopathic duct-centric pancreatitis. It affects people aged forty to fifty, men and women equally, and presents most often with recurrent acute pancreatitis or a pancreatic mass. It's confined to the pancreas, without systemic IgG4 elevation, and it's associated with inflammatory bowel disease, usually ulcerative colitis, in about thirty percent. So her normal IgG4 doesn't argue against it.

7:59Her biopsy and her course both follow from the type. Her biopsy shows the granulocytic epithelial lesion with fewer than ten IgG4-positive cells per high-power field. She gets the same induction with prednisone. But type two relapses infrequently, because the injury centered on the duct isn't driven by a circulating plasma-cell clone, so she needs no maintenance therapy, and a relapse would be treated with steroids again, as for the first episode.

8:25Here are the traps the boards set in these patients. Painless jaundice in an older man isn't always cancer. Severe pain isn't typical of autoimmune pancreatitis. The diagnosis isn't made on an IgG4 level alone, especially a mild elevation. Steroids aren't started for a focal mass before cancer has been excluded. Steroids aren't continued when there's no response at two weeks. A raised IgG4 isn't expected in type two. Type two is linked to ulcerative colitis. Type two doesn't need maintenance therapy. And relapsing type one is treated with rituximab.

9:01So, start to finish. Type one autoimmune pancreatitis is IgG4-related disease: an older man with painless jaundice, a sausage-shaped gland, a non-dilated irregular duct, and often other organs involved. Type two is a younger patient, often with ulcerative colitis, with recurrent pancreatitis or a mass and a normal IgG4, and its hallmark is the granulocytic epithelial lesion. The key decision is excluding cancer, because a mildly raised IgG4 occurs in adenocarcinoma, so the HISORt or international consensus criteria are applied before treating.

9:39Give prednisone, forty milligrams for four weeks, then taper by five milligrams a week. No response within two weeks means reconsidering cancer. Type one relapses in a third to a half of patients and is maintained with rituximab or an immunomodulator, while type two rarely relapses and needs no maintenance.

9:58Episode four turns to pancreatic cysts: the types, what the cyst fluid shows, intraductal papillary mucinous neoplasm risk features, and surveillance.

10:10For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode three of five of chapter twenty-six, and I'll see you in the next one.