Case Discussion <Presentation of a Case> This 71-year-old man visited the emergency room (ER) because of progressive itching and jaundice for 2 weeks This patient had hypertension and diabetes for which he had received oral antihypertensives and oral hypoglycemic agents for 30 years and 5 months, respectively; benign prostate hypertrophy and gall bladder stone fro which he underwent transurethral prostatectomy and laparoscopic cholecystectomy 7 and 2 years earlier, respectively. He had smoked for 50 year but had quitted 2 years earlier. He did not consume alcohol. He had been quite well before except mild acid regurgitation occasionally. About 2 weeks prior to this admission, progressive itching and jaundice developed and his appetite became poor . He lost weight by 15 kg over the past 5 months ( a weight change from 78 Kg to 63 Kg). In addition, tea-color urine and clay-color stool was noted for 1 week before entry. He sought medical attention at a local clinic and was transferred to an outside hospital because of jaundice. In the hospital, the level of bilirubin was 8.0 mg/dl and the sonography revealed mild dilatation of common bile duct (CBD) (13 mm) and a clear pancreatic shadow . The computed tomography (CT) of the abdomen revealed dilatation of CBD and intra-hepatic ducts (IHD) and the diagnosis of chronic pancreatitis was made. He then came to our ER for further help. On physical examination, this patient was clear in consciousness. The temperature was 36.6 0C, the pulse was 64 beats per minute and the respiration rate was 20 times per minutes. Blood pressure was 106/70 mmHg. His conjunctivae were pink and sclera were icteric. His neck was supple without lymphadenopathy. Chest examination showed symmetric expansion with clear breathing sound. No spider angioma or caput medusa was noted. Heart auscultation yielded regular heart beat without murmur. His abdomen was soft and flat and no tenderness or rebounding tenderness. The liver and spleen were not enlarged. Bowel sound was normoactive and his extremities had no edema. <Laboratory data> 1. Hemogram WBC RBC Hb HT MCV PLT K/uL M/uL g/dL % fL K/uL 7.85 4.04 11.9 35.3 87.4 260 Meta Band Seg Eos Baso Mono Lym 0 % 0 % 59.3 % 0.9% 0.3% 8.2 % 31.3 % Alb Glo T-Bil D-Bil AST ALP r-GT g/dL g/dL mg/dl mg/dl U/L u/L u/L 3.2 3.7 17.07 12.56 44 624 77 BUN CRE ALT GLU Amy Lip CEA CA19-9 mg/dl mg/dl U/L mg/dl 1 u/L u/L ng/mL u/mL 11.0 1.0 52 212 76 13 3.15 78.1 <Course and Treatment> At ER, abdominal sonography revealed dilatation of CBD & IHD and diffuse swelling of pancreas (Fig. 1 ) with a 3.2 cm hypoechoic lesion at the pancreatic head with reticular pattern (Fig. 2). The CT of the abdomen revealed diffuse dilatation of bilateral IHD (Fig. 3) with acute tappering of the distal CBD and a focal well-defined tumor at the pancreatic head (Fig. 4 ); and spotty calcifications were noted, which was suggestive of chronic pancreatitis. There was no evidence of CBD stone. The endoscopic retrograde cholangiopancreatography (ERCP) was performed but failed due to difficult cannulation. Under the impression of obstructive jaundice with chronic pancreatitis and pancreatitic head tumor , he underwent percutaneous transhepatic cholangiographic drainage (PTCD) and the jaundice improved gradually. A surgeon was consulted and Whipple operation was performed after his condition stabilized. Operative findings showed the whole pancreas tissue was firm, hard, and adhesive to the surrounding tissue. The pathology revealed chronic fibrosing pancreatitis with eosinophilia without evidence of malignancy. He was then discharged receiving outpatient follow-up. However, several episodes of pancreatitis occurred to him and were managed at outside hospitals. His diabetes became difficult to control. Elevated IgG (1730 mg/dL; normal range: 700-1600 mg/dL) and IgG4 (564 mg/dL; normal range: 60-130 mg/dL) were noted. ANA, C3 and C4 were relatively normal. Autoimmune pancreatitis was diagnosed from the clinical course and therefore prednisolone (10 mg tid) was given for 2 months and was tapered off gradually. His blood glucose became stabilized and he was doing well with during follow-up as an outpatient <Discussion and Analysis> Sarles el al. has reported a type of chronic pancreatitis with hyperglobulinaemia and probably an autoimmune mechanism. The nomenclature included autoimmune pancreatitis (AIP), sclerosing pancreatitis, primary inflammatory pancreatitis, lymphoplasmatocytic sclerosing pancreatitis (LPSP), chronic pancreatitis with irregular narrowing of the main pancreatic duct and sclerosing pancreatocholangitis. AIP has been associated with several autoimmune diseases, including Sjogren's syndrome, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), inflammatory bowel disease, retroperitoneal fibrosis, and autoimmune hepatitis. AIP usually presented with obstructive jaundice, weight loss, abdominal pain, general malaise, and DM. Hypergammaglobulinemia was its feature and maybe associated with elevated autoantibody titers (ANA, anti-lactoferrin antibod, anti-carbonic anhydrase II antibodies, RF). High levels of IgG and/or IgG4 was most characteristic. Radiologic findings included diffuse enlargement of the pancreas and focal masses in the pancreas. Pancreatic calcification or pseudocyst formation is seldom observed. ERCP may shown segmental or diffuse narrowing of the main pancreatic duct and frequent stenosis of the lower bile duct. MRCP is poor in showing stenosis of the pancreatic duct but it can adequately demonstrate stenosis of the bile ducts. Histologically, it showed a chronic, immune-mediated, fibroinflammatory process. Dense lymphocytic infiltrate centered around the medium-sized interlobular and large pancreatic ducts. Plasma cells , eosinophils and neutrophils infiltration may also be found. Clustering of lymphocytes around veins ('periphlebitis') with occasional obliterative phlebitis is another feature. The diagnosis of AIP was based in the combination of clinical, laboratory findings and imaging studies. Japan Pancreas Society has set a diagnostic criteria on 2002, which included: Pancreatic image studies show diffuse narrowing of the main pancreatic duct with irregular walls and diffuse enlargement of the pancreas; Laboratory data demonstrate abnormally elevated serum gamma-globulin, and/or IgG, or the presence of autoantibodies; Histopathological examination shows fibrotic changes with lymphocyte and plasma cell infiltration. The diagnosis of AIP is made when criteria 1 plus criteria 2 and/or 3 are met. DM is often (43-68%) present in patients with AIP, and the majority of them showed type 2 DM. Some type 2 DM patients associated with AIP improve after steroid therapy. The mechanism is still unclear. The relationship of AIP and pancreatic cancer deserves special attention. Clinical difficulties in differential diagnosis were the most important problem. They may share similar features such as frequent stenosis of the bile duct, elevation of serum CA 19-9, segmental pancreatic enlargement or narrowing of the main pancreatic duct. At least 5% of patients who undergo surgery for cancer of the head of the pancreas are found to have benign inflammatory disease The treatment of AIP was mainly based on steroid, which is usually effective for extra-pancreatic and pancreatic lesions. The jaundice sometimes needs PTCD or ERCP to relieve. Some patients may spontaneously improve. Surgical intervention may be necessary to those unresponsive to steroid therapy for symptomatic relief. Long-term prognosis of AIP remains unknown. <References> Ketikoglou I, et al. Dig Liver Dis. 2005;37(3):211-5 Okazaki K, et al. Gut 2002;51:1-4 Tanaka S, et al. Lancet 2000;356:910-1 Kamisawa T, et al. Am J Gastroenterol. 2003;98(12):2694-9 Van Gulik TM, et al. Gastrointest Endosc 1997;46: 417–23 Okazaki K, et al. Intern. Med. 2005; 44: 1215-1223 繼續教育考題 1. (C) Which one of the following diagnosis is the least likely differential diagnosis of AIP A Pancreatic head cancer B Chronic pancreatitis C Chronic hepatitis D Periampullary tumor 2. (C) What is the most proper management to treat AIP initially? A Surgical only B Long-term biliary stenting only C Steroid should be considered first D Supportive care 3. (C) Which one of the following is NOT the usual radiologic finding of AIP? A  Pancreatic focal mass B Pancreas swelling C Main panreatitc duct dilatation D Stenosis of distal common bile duct 4. (D) Which one of the following is NOT the usual laboratory finding of AIP? A Elevated IgG B Elevated IgG4 C Elevated bilirubin D Elevated CEA 5. (D) Which one of the following is NOT the usual clinical manifestation of AIP? A Jaundice B Weight loss C DM D Hypertension 6. (B) Which one of the following description about AIP is wrong? A AIP is sometimes difficult to differentiated from pancreatic head cancer B AIP is often associated with type 1 DM C DM may improve when AIP is under control D Pancreatic calcification or pseudocyst formation is seldom seen in AIP 答案解說 【C】 AIP usually manifested as obstructive jaundice and therefore should be differentiated with periampullary lesion, pancreatic head lesion or chronic pancreatic. 【C】 AIP could be treated with steroid first if the diagnosis has been made, since drug management was less invasive and carries less mortality and morbidity. 【C】 Diffuse pancreatic swelling with main pancreatic duct narrowing is a feature of AIP, which is in contrast to the MPD dilation of the pancreatic head cancer. 【D】 CA19-9 elevation was occasional observed in AIP patient, but not CEA elevation. 【D】 Hypertension is not a typical feature of AIP. 【B】 AIP is often associated with type 2 DM, not type 1 DM.