IgG4-related disease in Singapore: a description of two cases and review of the literature.

We describe a 42-year-old man who presented with painless obstructive jaundice, organomegaly and lymphadenopathy. Biopsy of the ampulla of Vater revealed the presence of increased populations of plasma cells which stained positively for immunoglobulin G4. He was treated with prednisolone and demonstrated significant clinical improvement 1 month later. A further case is described and a review of the literature is also provided.

Clinical significance of swollen duodenal papilla in autoimmune pancreatitis.

OBJECTIVES: To evaluate the clinical significance of a swollen main duodenal papilla and the associated immunohistopathologic findings in patients with autoimmune pancreatitis (AIP). METHODS: Seventeen consecutive patients with AIP registered between April 2001 and October 2005 who underwent both endoscopic retrograde cholangiopancreatography and endoscopic biopsy were enrolled in this study. The endoscopic features, stromal inflammatory cell infiltrate (SICI), and results of immunohistochemical examination of the duodenal papilla using IgG4, CD3, and CD79a antibodies were retrospectively reviewed. These findings in the AIP patients were compared with those in 12 patients with chronic alcoholic tumor-forming pancreatitis (CAP). The numbers of cells in the SICI and of IgG4-positive plasma cells per high-power field were counted in all the histopathologic specimens. RESULTS: A swollen main duodenal papilla was observed in 11 (11 [64.7%]/17) patients with AIP and 4 (4 [33.3%]/12) patients with CAP (P < 0.05). Resolution of the swollen main duodenal papilla was observed in all of these 11 patients with AIP (11 [100%]/11) in response to treatment with corticosteroids. On the other hand, the 6 patients without elevated serum IgG4 or a swollen duodenal papilla, but with a swollen pancreas, improved even without corticosteroid treatment. The number of cells in the SICI in the AIP patients was significantly higher than that in the CAP patients. Although in 13 of 17 AIP patients, infiltration by IgG4-positive plasma cells was detected in the duodenal papilla, no such significant infiltration of the duodenal papilla by IgG4-positive plasma cells was observed in the patients with CAP (P < 0.05). More predominant T-cell infiltration of the duodenal papilla was recognized in the AIP patients than in the CAP patients (P < 0.05). CONCLUSIONS: These results suggest that a swollen main duodenal papilla with IgG4-positive plasma cell and T-cell-dominant infiltration and an abundant stromal cell infiltrate are characteristic findings in AIP. We suggest that these findings may be valuable adjuncts to the diagnosis of AIP as well as for selecting suitable candidates for corticosteroid therapy.

[Autoimmune pancreatitis--a surgical disease?]. / Die autoimmune Pankreatitis--eine chirurgische Krankheit?

The term autoimmune pancreatitis (AIP) describes a nonalcoholic, chronic lymphoplasmocytic pancreatitis. The lymphoplasmocytic infiltration is characterized by periductal localization of predominantly CD4-positive T cells, fibrosis, and acinar atrophy, frequently resulting in stenosis of the main pancreatic and distal common bile ducts. Imaging studies often reveal a diffuse narrowing of the pancreatic main duct and swelling of the pancreatic head wrongly suggesting the presence of a malignant tumor. Clinical signs include mild abdominal pain, jaundice, recurrent episodes of acute pancreatitis, and even new-onset diabetes mellitus. Additionally, AIP can be associated with other autoimmune diseases such as Sjögren's syndrome, primary sclerosing cholangitis, chronic inflammatory bowel diseases, and retroperitoneal fibrosis. Serological markers include autoantibodies and increased levels of gamma globulin and especially IgG4. Steroids seem to be effective in improving clinical symptoms as well as in the resolution of pancreatic and bile duct narrowing. This distinguishes AIP from other forms of pancreatitis and from pancreatic neoplasms. Further studies of the underlying pathophysiologic mechanisms, prognosis, and new diagnostic tools are needed to provide adequate and effective treatment in the future. In this article, we summarize the current knowledge about AIP and present 17 cases that underwent surgical resection at our institution from 2003 to 2004.

Immunopathological study on the development of swine serum-induced bile duct lesions in BALB/c and DBA/2 mice.

To compare the difference in the development of swine serum (SS)-induced bile duct lesion (BDL) between high responder BALB/c and low responder DBA/2 mice, the mice of both strains injected with SS twice a week for up to 4 weeks were killed and examined immunopathologically after the 2nd, 4th, 6th and 8th SS-injection, respectively. In BALB/c mice, BDL developed rapidly following the SS-injections, and a slight enlargement of common bile ducts accompanied with infiltration of T helper cells and eosinophils was detected after the 2nd SS-injection. From the 4th injection on, BDL was characterized by proliferation of mucous glands, hyperplasia and hypertrophy of biliary and glandular epithelial cells, periductal fibrosis, infiltration of eosinophils, plasma cells and T helper cells, and increase of mast cells, resulting in more apparent enlargement of common bile ducts. Several hypertrophied biliary and glandular epithelial cells were positive for mouse immunoglobulins and SS. BDL subsided after cessation of the SS-treatment. On the other hand, in DBA/2 mice, immune response and inflammatory reaction were very weak, and only slight BDL were detected.

Effects of relief of biliary obstruction on mononuclear phagocyte system function and cell mediated immunity.

Obstructive jaundice causes depression of immune system function but it is unclear at present how rapidly immune function recovers after relief of biliary obstruction. To address this issue, we studied 218 Sprague-Dawley rats with common bile duct obstruction. Mononuclear phagocyte function, cell mediated immune function, portal-systemic shunt fraction, liver function tests, and liver histology were evaluated in normal (sham) rats, obstructed rats, and at weekly intervals after relief of biliary obstruction. Hepatic uptake of radiolabelled bacteria was 82 per cent in sham rats and 66 per cent in rats 21 days after CBD obstruction (P less than 0.05). Phagocytic activity returned to normal within 7 days after choledochoduodenostomy. Cell mediated immunity, measured by skin graft rejection, was significantly prolonged in the obstructed group (P less than 0.05) but had returned to normal 7 days after biliary diversion. Return of hepatocellular function, as measured by liver function tests, paralleled recovery of immune function. This study demonstrates prompt recovery of the immune system after internal biliary drainage for obstructive jaundice. This finding is in contrast to previous studies that demonstrated persistent immune suppression months after biliary diversion. These data may have implications concerning the usefulness of internal biliary drainage before surgery in patients with obstructive jaundice.

Impaired specific cell-mediated immunity in experimental biliary obstruction and its reversibility by internal biliary drainage.

Little is known of the effect of cholestasis on host immunity. This study evaluates lymphocytic responsiveness to PHA and LPS mitogen and to allogeneic F344 antigen in Sprague-Dawley rats 21 days following bile duct ligation and 31 days following relief of jaundice by internal biliary drainage. Serum bilirubin level was significantly elevated in the bile duct ligated animals at Day 21 (P less than 0.001) and thereafter returned to preoperative levels following internal biliary drainage. Results demonstrate depressed responsiveness to PHA (P less than 0.001) and allogeneic F344 antigen in vivo (P less than 0.04) and in vitro (P less than 0.02) in bile duct ligated animals as compared to sham, sham pair-fed, and normal control rats. The observed deficiency in responsiveness to T-cell-dependent mitogen and antigen cannot be explained on the basis of complicating nutritional, renal, or infective factors. Subsequent internal biliary drainage results in some improvement in T-cell responsiveness in the bile duct ligated group although recovery is not complete. B-Lymphocytic response to LPS mitogen is not affected by bile duct ligation. We conclude that cholestasis subsequent to extrahepatic biliary obstruction per se results in impairment of cell-mediated immunity in vivo. This impairment is partly reversible by internal biliary drainage. In vitro B-cell function does not appear to be affected in this model. Further study of impaired cell-mediated immunity in extrahepatic biliary obstruction will improve our understanding of the immunological status of patients with obstructive jaundice and cholestatic liver diseases.