Purpose: Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by high serum IgG4 concentrations and abundant IgG4 bearing plasma cell infiltration in the pancreatic lesion, and has been reported to be associated with a variety of extra-pancreatic lesions, leading us to postulate the concept of systemic inflammatory disease. To confirm this, we attempted to clarify the exact distribution of and provide a panoramic view of these extra-pancreatic lesions. Methods: The frequency, distribution, clinical characteristics, and pathology of five extra-pancreatic lesions were determined in 64 patients with autoimmune pancreatitis by examining clinical and laboratory findings. Results The most frequent extra-pancreatic lesion was hilar lymphadenopathy (80.4%), followed by extra-pancreatic bile duct lesions (73.9%), lachrymal and salivary gland lesions (39.1%), hypothyroidism (22.2%), and retroperitoneal fibrosis (12.5%). No patients had all of five lesions. Patients with hilar lymphadenopathy or lachrymal and salivary gland lesions were found to have significantly higher IgG4 levels than those without (p=0.0042, 0.0227, respectively). Patients with 3 lesions were found to have significantly higher IgG4 levels than those with no lesion, suggesting that patients with multiple extra-pancreatic lesions represent an active state of the disease. Similar to pancreatic lesions, extra-pancreatic lesions have a characteristic histological finding of abundant IgG4 bearing plasma cell infiltration, and they respond favorably to corticosteroid therapy. Conclusion: Autoimmune pancreatitis can be recognized as systemic inflammatory disease. Furthermore, recognition of these characteristic findings will aid in correct diagnosis of this disease.

Purposes: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely used for the diagnosis of pancreatic cancer. Because autoimmune pancreatitis is easily misdiagnosed as pancreatic cancer and can be tested for by FDG-PET analysis based on the presence of suspected pancreatic cancer, we attempted to clarify the differences in FDG-PET findings between the two conditions. Methods: We compared the FDG-PET findings between 15 patients with autoimmune pancreatitis and 26 patients with pancreatic cancer. The findings were evaluated visually or semiquantitatively using the maximum standardized uptake value and the accumulation pattern of FDG. Results: FDG uptake was found in all 15 patients with autoimmune pancreatitis, whereas it was found in 19 of 26 patients (73.1%) with pancreatic cancer. The accumulation pattern of nodular shape was frequently seen in pancreatic cancer with significance, whereas a longitudinal shape indicated the existence of autoimmune pancreatitis. Heterogeneous accumulation was found in almost all cases of autoimmune pancreatitis, whereas homogeneous accumulation was found in pancreatic cancer. Most cases of pancreatic cancer showed solitary localization with significant difference, whereas multiple localizations in the pancreas favored the existence of autoimmune pancreatitis. FDG uptakes in the hilar lymph node were more frequently seen in autoimmune pancreatitis than in pancreatic cancer with significance, and those in the lachrymal gland, salivary gland, biliary duct, retroperitoneal space, and prostate were only seen in autoimmune pancreatitis. Conclusions: FDG-PET provides a useful tool for differentiating autoimmune pancreatitis from suspected pancreatic cancer, if its accumulation pattern and extra-pancreatic involvements are considered. IgG4 measurement and other current image tests will confirm further diagnosis.

Well over six decades since its first description, the Rheumatoid Factor (RF)—autoantibodies recognizing Fc (constant) portion of IgG through their own Fab (antigen binding variable segments)—is believed to have come of age. Autoimmune pancreatitis is a unique form of pancreatitis, biologically characterized by an elevated serum IgG4 concentration. Given the fact that IgG4 myeloma proteins can act as RF, we initially hypothesized that IgG4 in autoimmune pancreatitis might do likewise, hence potentially contributing to disease pathogenesis. Indeed Western blotting clearly showed that IgG4 binds to IgG1 κ, IgG2 κ, IgG3 κ myeloma proteins, as well as to IgG Fc, in line with a typical RF activity. Further experiments however unraveled the unexpected fact that unlike hitherto known RF, IgG4 does not engage IgG Fc through its Fab, but its very own Fc. These data therefore collectively describe a Novel RF (NRF) in autoimmune pancreatitis. In the future, the relevance of NRF, beyond autoimmune pancreatitis, in both diagnosis/prognosis as well as pathophysiology of autoimmune and other systemic diseases where IgG4's role seems paramount, needs to be systematically assessed.

Autoimmune pancreatitis is a unique disease, characterized by lymphoplasmacytic inflammation in the acute stages. However, the active clinical features are unlikely to persist for longer periods. Through long-term follow-up, we investigated the disease course in 51 patients with autoimmune pancreatitis. We found recurrence in 21 (41%) and pancreatic stone formation in 9 (18%) patients. Pancreatic stone formation was significantly more frequent in the recurrence group (7/21; 33%), compared to the non-recurrence group (2/30; 7%). Moreover, we found high serum immunoglobulin-G4 concentrations in 13 of 175 (7.4%) patients with ordinary chronic pancreatitis. This suggested that pancreatic stone formation was closely associated with recurrence and that autoimmune pancreatitis may transform into ordinary chronic pancreatitis after several recurrences. We found that the immune complex level, with a cut-off value of 10 mg/dl, served as a good predictor of recurrence, with high sensitivity (61.9%), specificity (70.0%) and efficacy (66.7%). We also confirmed that human leukocyte antigen and cytotoxic T-lymphocyte antigen-4 polymorphism were useful predictors for autoimmune pancreatitis recurrence.3

Risk factors for pancreatic stone formation in autoimmune pancreatitis over a long-term course