Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies.
Autoimmune Diseases/*immunology ; Cholangitis, Sclerosing/*immunology ; Humans ; Immunoglobulin G/*immunology ; Lacrimal Apparatus/immunology ; Lymphatic Diseases/*immunology ; Pancreatitis, Chronic/*immunology ; Salivary Glands/immunology ; Sclerosis/immunology

Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and deveolpment of pancreatitis. A hallmark of the inflammatory response is the induction of cytokine gene expression, which may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-KB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H2O2 and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by N-acetylcysteine (NAC) and superoxide dismutase (SOD). ROS generation in neutrophils increased by PMA, which was inhibited by NAC and SOD. The productions of H2O2, LPO and TNF-alpha were increased with the amounts of PMA-primed neutrophils added to acinar cells while the productions of H2O2, LPO and cytokines increased with time. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer). Both NAC and SOD inhibited neutrophil-induced alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatory cytokines in acinar cells. Antioxidants such as NAC might be clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-KB and decreasing cytokine production.
Acute Disease ; Chronic Disease ; Cytokines/immunology* ; Human ; NF-kappa B/metabolism* ; Pancreas/metabolism* ; Pancreas/immunology* ; Pancreas/cytology ; Pancreatitis/metabolism ; Pancreatitis/immunology ; Support, U.S. Gov't, Non-P.H.S.

No abstract availble.
Autoimmune Diseases/*drug therapy ; Glucocorticoids/*therapeutic use ; Humans ; Pancreatitis, Chronic/*drug therapy/immunology

BACKGROUND/AIMS: Autoimmune pancreatitis is a distinctive type of chronic pancreatitis with reversibility. We analyzed the largest number of patients with autoimmune pancreatitis among the studies carried out at a single institution in Korea. METHODS: We retrospectively analyzed the clinical, radiologic, laboratory and histologic features in 17 patients who were diagnosed as autoimmune pancreatitis. RESULTS: The patients were predominately elderly men who presented with jaundice or nonspecific gastrointestinal symptoms. In most of the patients, serum pancreatic enzymes were normal or mildly elevated with an accompanying cholestatic biochemical profile. Elevated IgG levels and detection of autoantibodies were observed in 47% (8/17) and 35% (6/17), respectively. Thirteen patients showed histologic findings of lymphoplasmacytic infiltration and fibrosis, and one patient showed predominant infiltration of eosinophils. Fifteen patients revealed radiologic images of diffuse swelling of pancreas and the sclerosing pattern on direct pancreatogram. All of the features improved in response to oral steroid therapy. Two cases showed focal narrowing with upstream duct dilatation and thus, they were diagnosed as focal type. Diabetes mellitus concurred in 13 cases and primary sclerosing cholangitis and Sjogren's syndrome were present in 1 case, respectively. CONCLUSIONS: The recognition of autoimmune pancreatitis allows patients to avoid unnecessary surgery and recover with the administration of oral steroid.
Aged ; Autoimmune Diseases/*diagnosis/pathology ; Chronic Disease ; English Abstract ; Humans ; Male ; Middle Aged ; Pancreas/pathology ; Pancreatitis/*diagnosis/immunology/pathology

BACKGROUND/AIMS: To diagnose autoimmune pancreatitis (AIP), serum IgG and IgG4 concentration are significant serologic markers. The purpose of this study was to assess the utility of serum IgG and IgG4 for the diagnosis of AIP. METHODS: We divided enrolled patients into 2 groups: autoimmune pancreatitis and other pancreatic disease. We measured serum IgG and IgG4 levels in patients including 12 AIP and 23 other pancreatic disease. RESULTS: Among AIP patients, 10 cases (83%) showed elevated IgG4 levels of more than 135 mg/dL and 4 cases (33%) showed elevated IgG levels of more than 1,800 mg/dL, the current cutoff value applied in Japan. Only one patient showed elevated serum IgG level, despite having normal IgG4 level. Sensitivity and specificity for AIP of elevated serum IgG4 (>135 mg/dL) were 91% and 92%, and for elevated serum IgG (>1,800 mg/dL) 67% and 92%, respectively. The optimal cut-off level of IgG4 using receiver operation characteristic (ROC) was 127 mg/dL, at which the sensitivity and specificity were 83% and 96%, respectively, for the diagnosis of AIP. Serum IgG at 1,520 mg/dL showed the sensitivity and specificity of 83% and 87%, respectively. CONCLUSONS: The measurement of serum IgG and IgG4 are helpful to diagnose AIP. Serum IgG and IgG4 are complementary to each other in the diagnosis of AIP.
Adult ; Aged ; Autoimmune Diseases/*diagnosis/immunology ; Biological Markers/blood ; Diagnosis, Differential ; Female ; Humans ; Immunoglobulin G/*blood ; Male ; Middle Aged ; Pancreatitis, Chronic/*diagnosis/etiology/immunology ; ROC Curve ; Sensitivity and Specificity

BACKGROUND/AIMS: Autoimmune chronic pancreatitis (AIP) is a clinically attractive entity because of its dramatic response to steroid therapy. But the long-term results after steroid therapy have not been reported yet in Korea. The purpose of this study was to assess the long-term results and prognosis after steroid therapy in patients with AIP. METHODS: We retrospectively analyzed the clinical, radiologic, and laboratory features and evaluated clinical outcomes in 19 patients with AIP who have been treated with oral corticosteroid. All patients were initially treated with prednisolone (30-40 mg/d) for 1 or 2 months. After the confirmation of clinical improvement in radiologic imaging and laboratory findings, the daily dose of prednisolone was then gradually tapered by 5-10 mg per month to the maintenance dose (2.5-7.5 mg/d). RESULTS: All the patients showed normalization or marked improvement in symptoms, laboratory and imaging findings after steroid therapy. There were 4 cases (21%) of recurrence during the mean follow-up period of 27 months. All the patients with recurrence responded to oral steroid again. Among the 10 patients with diabetes mellitus, seven patients were able to stop or reduce the medication for diabetes after completion of steroid therapy. The biliary stents were additionally inserted in 10 patients who showed distal common bile duct stricture and obstructive jaundice. The accompanying autoimmune diseases were also improved with oral corticosteroid. CONCLUSIONS: Steroid therapy is very effective for AIP and is also effective in the cases of recurrence. A definitive protocol of steroid therapy for AIP should be established in the future.
Administration, Oral ; Adult ; Aged ; Autoimmune Diseases/*drug therapy ; Female ; Glucocorticoids/*administration & dosage ; Humans ; Male ; Middle Aged ; Pancreatitis, Chronic/*drug therapy/immunology ; Prednisolone/*administration & dosage ; Recurrence

BACKGROUNDThe prevalence of chronic pancreatitis has increased during recent years in Asia-Pacific areas as well as in China. The etiologies vary in different regions and periods. This study aimed to investigate the changing etiologies of chronic pancreatitis within 20 years at Peking Union Medical College Hospital in China.

METHODSRetrospective analysis of the etiologies of 636 cases of chronic pancreatitis at Peking Union Medical College Hospital from 1990 to 2010 was performed. Patients were divided into two groups according to two time periods (1990 - 2000 and 2001 - 2010). Statistical analysis was performed using the chi-square test.

RESULTSThe morbidity rate of chronic pancreatitis in China has recently increased. The main etiology changed from biliary diseases in the 1990s (decreased from 36.8% to 28.1%) to alcohol abuse after the year 2000 (increased from 26.5% to 36.8%). The main etiology of biliary diseases is stones in the cholecyst or bile duct, and the percentage of cholecystitis cases has increased. Autoimmune disease, including autoimmune pancreatitis, has increased quickly and currently accounts for 7.3% of cases because a greater number of autoimmune pancreatitis cases are being diagnosed. Approximately 9.5% of chronic pancreatitis cases are caused by multiple factors such as alcohol abuse and bile duct stones. Other factors include cholecystectomy and acute pancreatitis.

CONCLUSIONSThe main etiology of chronic pancreatitis has changed from biliary disease to alcohol abuse in recent years. Autoimmune factors have also obviously increased.

Adult ; Alcoholism ; complications ; Bile Duct Diseases ; complications ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis, Chronic ; epidemiology ; etiology ; immunology ; Retrospective Studies ; Risk Factors

OBJECTIVETo investigate clinicopathological features of fibrous mass-forming chronic pancreatitis (FMCP), to compare clinicopathological and immunohistochemical characteristics between autoimmune pancreatitis (AIP) and fibrous mass-forming non-autoimmune pancreatitis (nAIP) and to provide evidence for pathological diagnosis, differential diagnosis and clinical treatment strategy.

METHODSClinicopathological features were analyzed in 81 cases of FMCP. Infiltrating IgG4(+) plasmacytes were counted by immunohistochemical staining.

RESULTSAmong 81 cases of FMCP, 20 cases were diagnosed as AIP and 61 cases were interpreted as nAIP. AIP was more common in males over 50 years, whereas nAIP was seen in much younger patients (P = 0.001). The amount of inflammatory cells in the stroma of AIPs was remarkable higher than that in nAIPs (P = 0.002). The incidence of neuritis in AIPs (100%, 20/20) was also higher compared with that of nAIPs (75.4%, 46/61; P = 0.017). Storiformed-fibrosis was more common in AIPs (95.0%, 19/20) than in nAIPs (1.6%, 1/61;P = 0.000). Pancreatic intraepithelial neoplasia (PanIN) was observed in 50.0%(10/20) of AIPs and 32.8%(20/61) of nAIPs, with a greater severity observed in AIPs (P = 0.031). Tubular complex (TC) was more commonly observed in AIPs (65.0%, 13/20) than nAIPs (26.2%, 16/61;P = 0.002). Among 81 cases of FMCP, 61 cases had less than 11 IgG4(+) plasmacytes /HPF, 7 cases had 10-30/HPF and 13 cases had over 30/HPF.

CONCLUSIONSFMCPs include both AIP and nAIP. AIP has distinct pathological features and the presence of IgG4(+) plasmacyte is an important diagnostic parameter. FMCP appears to be an important precancerous lesion of pancreatic ductal adenocarcinoma. Surgery may be considered for patients with FMCP due to its mass-forming nature. In contrast, patients with AIP are treated medically due to its steroid-responsiveness. Therefore, accurate and timely diagnosis of AIP is of clinical relevance to avoid unnecessary surgical complications and to prevent progression of the disease.

Adult ; Aged ; Autoimmune Diseases ; immunology ; pathology ; surgery ; Carcinoma, Pancreatic Ductal ; immunology ; pathology ; surgery ; Diagnosis, Differential ; Female ; Fibrosis ; Humans ; Immunoglobulin G ; metabolism ; Male ; Middle Aged ; Pancreas ; pathology ; Pancreatic Neoplasms ; immunology ; pathology ; surgery ; Pancreatitis, Chronic ; immunology ; pathology ; surgery ; Plasma Cells ; immunology ; Precancerous Conditions ; immunology ; pathology ; surgery ; Young Adult

Autoimmune chronic pancreatitis is a disease characterized by diffuse swelling of the pancreas, irregular narrowing of the main pancreatic duct and elevated levels of serum IgG, and lymphoplasmacytic infiltration is observed on histologic examination. Steroid therapy can dramatically reverse the clinical symptoms and the histologic and radiologic findings. It is known that recurrence is very rare after successful steroid treatment. Furthermore, there have not yet been any reports about a case that relapsed during maintenance therapy with low dose steroid. We experienced a rare case of autoimmune chronic pancreatitis that relapsed despite maintenance therapy with low-dose steroid, and the patient again responded to high-dose steroid.
Administration, Oral ; Autoimmune Diseases/*drug therapy/immunology/radiography ; Cholangiopancreatography, Endoscopic Retrograde ; Chronic Disease ; Dose-Response Relationship, Drug ; Follow-Up Studies ; Glucocorticoids/administration & dosage/*therapeutic use ; Humans ; Male ; Middle Aged ; Pancreatitis/*drug therapy/immunology/radiography ; Prednisolone/administration & dosage/*therapeutic use ; Recurrence ; Tomography, X-Ray Computed