Question: A 64-year-old man experienced acute episodes of abdominal and back pain 5 months ago, followed by jaundice, which prompted him to seek evaluation at his local hospital. Laboratory evaluation was notable for elevated bilirubin 3.4 mg/dL (reference range, 0–1.2 mg/dL), alkaline phosphatase of 1352 U/L (reference range, 50–121 U/L), alanine aminotransferase of 219 U/L (reference range, 12–52 U/L), and lipase 361 U/L (reference range, 13–78 U/L). The patient underwent several endoscopic retrograde cholangiopancreatography (ERCP) procedures with brush cytology and common bile duct (CBD) stent placement for an indeterminate stricture, and endoscopic ultrasound (EUS) examination with fine needle aspiration of the stricture without an identifiable etiology. At presentation for a second opinion, the patient noted resolution of jaundice, but complained of pruritus, greasy stools, flatulence, and bloating, along with a 30-lb weight loss and fatigue. He denied excessive alcohol consumption, smoking, or a history of gallstones. On physical examination, the patient was without jaundice or abdominal pain. Routine laboratory evaluation was unremarkable except for a mildly elevated alanine aminotransferase of 56 U/L and alkaline phosphatase of 260 U/L. Carbohydrate antigen 19-9 and alpha fetoprotein levels were within normal limits. Hepatitis B and C serologies, anti–smooth muscle actin and anti–mitochondrial antibodies were unremarkable. IgG4 subclass was elevated at 172 mg/dL (reference range, 2.4–121 mg/dL). A magnetic resonance cholangiopancreatography showed enhancement of the CBD with mural thickening and pancreatic parenchymal atrophy (Figure A). A repeat ERCP did not show significant intrahepatic biliary duct dilation, but a stricture was noted in the distal CBD. EUS examination demonstrated pancreatic body and tail atrophy with pancreatic head changes consistent with moderate to severe chronic pancreatitis. The entire visualized CBD and cystic duct had circumferential wall thickening (Figure B). Cholangioscopy showed nonspecific findings. Based on the clinical scenario and images, what is the most likely diagnosis? Look on page 827 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Cholangioscopic biliary mucosal biopsies showed active chronic inflammation and increased IgG4-positive cells. Pancreatic head biopsies showed fibrosis with lymphoplasmacytic infiltrate and increased IgG4-positive cells with an IgG4 to IgG ratio of >40%. Cytology and fluorescence in situ hybridization of bile duct brushings were again unremarkable. The patient was initiated on pancreatic enzyme replacement therapy and a slow taper of prednisone. On follow-up 3 months later, his gastrointestinal symptoms had resolved, and weight had stabilized. Likewise, his liver chemistries and IgG4 subclass level had normalized. Follow-up ERCP revealed improvement in the CBD stricture. IgG4-related disease (IgG4-RD) is an immune-mediated, fibroinflammatory, multiorgan disease. It can present with regions of inflammatory thickening or mass formation that is often confused for a malignancy. The disease presents insidiously and is progressive. Most frequently involved organs include the pancreas resulting in type 1 autoimmune pancreatitis with diffuse enlargement, diabetes, and exocrine insufficiency; salivary and lacrimal glands resulting in asymptomatic symmetric enlargement; retroperitoneum resulting in soft tissue mass; and bile ducts resulting in intrahepatic and extrahepatic strictures.1Perugino C.A. Stone J.H. IgG4-related disease: an update on pathophysiology and implications for clinical care.Nat Rev Rheumatol. 2020; 16: 702-714Crossref PubMed Scopus (90) Google Scholar Additionally, our patient had a diffusely thickened CBD and cystic duct wall well-characterized by EUS examination (Figure B). The diagnosis is based on a comprehensive workup to distinguish from conditions presenting similarly. In this case, pancreatic cancer, cholangiocarcinoma, and primary sclerosing cholangitis were carefully ruled out. Various criteria have been proposed to diagnose IgG4-RD that predominantly rely on (1) imaging features, (2) an elevated serum IgG4 with various cut-off values, and (3) histological findings of lymphoplasmacytic infiltrate with fibrosis, a ratio of IgG4-positive plasma cells/IgG-positive cells of >40%, and the number of IgG4-positive plasma cells greater than 10 per high-powered fields, and typical fibrosis, storiform, or obliterative phlebitis.2Löhr J.M. Beuers U. Vujasinovic M. et al.European guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations.United European Gastroenterol J. 2020; 8: 637-666Crossref PubMed Scopus (0) Google Scholar,3Umehara H. Okazaki K. Kawa S. et al.The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD.Mod Rheumatol. 2021; 31: 529-533Crossref PubMed Scopus (77) Google Scholar Multiple organ involvement and steroid responsiveness are also considered supportive of IgG4-RD. Our patient met the diagnostic criteria for IgG4-RD with excellent response to steroid treatment.
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Jul 15, 2024
Fumimasa Tomooka + 16
Open Access
