Diffuse Pancreatic Swelling Research Articles

Highly Active State of Autoimmune Pancreatitis With Mikulicz Disease

Patients with autoimmune pancreatitis (AIP) sometimes present with Mikulicz disease (MD); however, the clinical features regarding these AIP patients with MD have not yet been fully elucidated. Our aim is to study the clinical differences between AIP with and without MD. Twenty-eight AIP patients were divided into 2 groups, one with MD and one without it. The following factors having a possible association with the presence or absence of MD were investigated: sex; serum IgG and IgG4 levels; the presence or absence of antinuclear autoantibodies, jaundice, diabetes mellitus, swollen duodenal papilla, diffuse pancreatic swelling, spontaneous remission, and relapse. The MD and non-MD groups consisted of 5 AIP and 23 AIP patients, respectively. The results of univariate analysis revealed that AIP patients presenting with MD were significantly associated with a younger onset, female predominance, high serum IgG4 titer, and diffuse pancreatic swelling (P < 0.05). In 4 of the MD patients, onset preceded pancreatitis. Autoimmune pancreatitis patients presenting with MD tended to have different clinical features from the non-MD AIP patients, such as having an earlier onset, female tendency, and diffuse pancreatic swelling with a high titer of serum IgG4. Autoimmune pancreatitis with MD tended to precede gastroenterological events.

Three Clinicopathological Subtypes of Autoimmune Pancreatitis Stratified By the Duodenal Papillary Findings and the Serum IgG4

Background: The majority of cases with autoimmune pancreatitis (AIP) respond well to steroid therapy, some cases show spontaneous remission, while others develop a refractory course. The clinical differences between these three types of AIP have not yet been fully elucidated. Aim: To study the clinicopathological differences among the three aforementioned types of AIP. Patients and Methods: Thirty-one consecutive patients of AIP who underwent ERCP between April 2001 and November 2007 were identified from our database. The patients were stratified by the serum IgG4 level into three subtypes. (Group A: IgG4 < 135 mg/dl; B:IgG4 135-1000 mg/dl; C: IgG4 > 1000 mg/dl). We conducted a retrospective review to determine whether the following factors might be useful in distinguishing among the three subgroups of patients with AIP; serological data, presence/absence of obstructive jaundice, presence/absence of sclerosing cholangitis affecting the hilar bile duct, duodenal papillary findings (presence/absence of swelling), distribution of the pancreatic swelling (local/diffuse), and presence/absence of complicating extrapancreatic lesions. The histopathological differences in the duodenal papilla were also examined. Results: There were 11, 17 and 3 patients, respectively, in Groups A, B and C. Group C showed a younger onset, with a higher frequency of bronchial asthma, sclerosing sialadenitis, sclerosing cholangitis and relapse. The results of univariate analysis revealed that group C patients were significantly younger (Group A, 68 years; B, 68 years; C, 50 years), and showed significantly higher frequencies of a swollen duodenal papilla (Group A, 9%; B, 76.4%; C, 100%) and diffuse pancreatic swelling (Group A, 0%; B, 52.9%; C, 100%) (p < 0.05). Histopathological examination revealed marked stromal lymphoplasmocytic infiltration with an abundance of IgG4-positive plasma cells (cells / high power field) in the duodenal papilla in group C (Group A, 3/HPF; B, 17/HPF; C, 25/HPF). Conclusions: Our results suggest that AIP can be classified into 3 subgroups; AIP cases showing spontaneous remission, those with typical AIP responding to steroid therapy, and those with refractory AIP showing high titers of serum IgG4, younger onset, and high frequencies of bronchial asthma, swelling of the duodenal papilla with abundant IgG4-positive plasma cell infiltration, sclerosing sialadenitis and diffuse pancreatic swelling. This last group of AIP patients should be distinguished from those with typical AIP and should be treated with great caution because of the high frequency of relapse in these patients. Towards this end, examination of the duodenal papilla may pay rich dividends.

Mikulicz's disease and systemic IgG4-related plasmacytic syndrome (SIPS)

Mikulicz's disease represents persistent enlargement of the lacrimal and salivary glands, and autoimmune pancreatitis is shown with diffuse pancreatic swelling. Both diseases are characterized with elevated IgG4 concentrations in the serum and prominent infiltration by plasmacytes expressing IgG4 in the glands. Clinical analyses were performed in 40 patients with systemic IgG4-related plasmacytic syndrome (SIPS) who consulted the doctors in Sapporo Medical University Hospital. Our patients were mainly middle-aged or elderly females. The average age was 58.9 years. The diagnosis was following ; 33 cases with Mikulicz's disease, 3 cases with Küttner's tumor, and 4 cases with IgG4-related dacryoadenitis. Slight dysfunction of lacrimal and salivary gland was observed in about 60% of them. Antinuclear antibodies were detected in only 15% of the cases with SIPS. Almost all, except one case, did not have anti-SS-A or anti-SS-B antibodies. Interestingly, hypocomplementemia was revealed in 30% of them. The complications of SIPS include autoimmune pancreatitis, tubulointerstitial nephritis, retroperitoneal fibrosis, prostatitis, and so on. SIPS is mainly treated by the administration of steroids. We started to prescribe much quantity of prednisolone to the patients with organ failure. The recurrence was admitted in the 3 patients for the followed 16 years. We present here the problems and prospects in SIPS.

Clinical factors predictive of spontaneous remission or relapse in cases of autoimmune pancreatitis

The rates of spontaneous remission and relapse of autoimmune pancreatitis (AIP) are not known. To study the clinicopathologic factors predictive of remission and relapse in cases of AIP. Retrospective study. Of the 20 patients with AIP, complete response to steroid therapy was recognized in 12 patients, and the remaining 8 patients improved without steroid therapy. Seven patients experienced a relapse. Patients who were seronegative for immunoglobulin (Ig) G4, had no obstructive jaundice, no diabetes mellitus, no swelling of the duodenal papilla, negative staining of the duodenal papilla for IgG4, and focal pancreatic swelling showed a greater tendency toward spontaneous remission (P < .05). The results of multivariate analysis revealed that negative staining of the duodenal papilla for IgG4 was the only independent predictor of spontaneous remission of AIP (odds ratio [OR] 1.395, P = .0304). Seropositivity for IgG4, diffuse swelling of the pancreas, and the presence of stricture in the lower part of the bile duct were significantly associated with a relapse of AIP (P < .05) according to the results of univariate analysis, whereas the results of multivariate analysis revealed only diffuse pancreatic swelling as an independent predictor of a relapse of AIP (OR 26.197, P = .0331). Endoscopic findings are of useful prognostic value, because patients with AIP and with negative staining of the duodenal papilla for IgG4 appeared to have a higher frequency of remission without steroid therapy. Patients with AIP and with diffuse pancreatic swelling were found to be at an increased risk of relapse after the initial steroid administration.

Autoimmune pancreatitis: Functional and morphological recovery after steroid therapy

Autoimmune pancreatitis, a recently recognized type of chronic pancreatitis, is not rare in Japan, but reports of it elsewhere are relatively uncommon. We report the first preoperatively diagnosed case of autoimmune pancreatitis in Hungary, which responded well to steroid treatment and provided radiographic and functional evidence of this improvement. A 62-year-old female presented with a 4-month history of recurrent epigastric pain and a 5-kg weight loss. The oral glucose tolerance test (OGTT) indicated diabetes mellitus and the result of the fecal elastase test was abnormal. Ultrasonography (US) and the CT scan demonstrated a diffusely enlarged pancreas, and endoscopic retrograde cholangiopancreatography (ERCP) an irregular main pancreatic duct with long strictures in the head and tail. Autoimmune pancreatitis was diagnosed. The patient was started on 32 mg prednisolone daily. After 4 wk, the OGTT and faecal elastase test results had normalized. The repeated US and CT scan revealed a marked improvement of the diffuse pancreatic swelling, while on repeated ERCP, the main pancreatic duct narrowing was seen to be ameliorated. It is important to be aware of this disease and its diagnosis, because AIP can clinically resemble pancreatobiliary malignancies, or chronic or acute pancreatitis. However, in contrast with chronic pancreatitis, its symptoms and morphologic and laboratory alterations are completely reversed by oral steroid therapy.

Autoimmune pancreatitis with IgG4-positive plasma cell infiltration in salivary glands and biliary tract

A 62-year-old male was referred to our hospital because of liver dysfunction, diffuse pancreatic swelling, and trachelophyma. At admission, the patient was free of pain. Physical examination showed enlarged and palpable bilateral submandibular masses, but no palpable mass or organomegaly in the abdomen. Laboratory findings were as follows: total protein 90 g/L with gamma-globulin of 37.3% (33 g/L), total bilirubin 4 mg/L, aspartate aminotransferase 39 IU/L, alanine aminotransferase 67 IU/L, gamma-glutamyl transpeptidase 1 647 IU/L, and amylase 135 IU/L. Autoantibodies were negative, and tumor markers were within the normal range. Serum IgG4 level was markedly elevated (18 900 mg/L). Computed tomography (CT) showed diffuse swelling of the pancreas and dilatation of both common and intra-hepatic bile ducts. Endoscopic retrograde pancreatography (ERP) revealed diffuse irregular and narrow main pancreatic duct and stenosis of the lower common bile duct. Biopsy specimens from the pancreas, salivary gland and liver showed marked periductal IgG4-positive plasma cell infiltration with fibrosis. We considered this patient to be autoimmune pancreatitis (AIP) with fibrosclerosis of the salivary gland and biliary tract, prescribed prednisolone at an initial dose of 40 mg/d. Three months later, the laboratory data improved almost to normal. Abdominal CT reflected prominent improvement in the pancreatic lesion. Swelling of the salivary gland also improved. At present, the patient is on 10 mg/d of prednisolone without recurrence of the pancreatitis. We present here a case of AIP with fibrosclerosis of salivary gland and biliary tract.

A case of Mikulicz's disease complicated by autoimmune pancreatitis, in which impaired glucose tolerance was improved by glucocorticoid treatment

A 73-year-old woman had experienced dry mouth and swellings of both upper eyelids from 1998. In October 2003, she also developed bilateral submandibular swellings, and was diagnosed with diabetes mellitus and prescribed antidiabetic medication. She consulted our hospital in the summer of 2004 due to the exacerbation of eyelid swelling, and was admitted in October 2004. Keratoconjunctivitis sicca was not present. CT and MRI of the head showed bilateral enlargement of the lacrimal and submandibular glands. Serological investigations revealed hypergammaglobulinemia, but as antinuclear antibody and anti-SS-A antibody were absent, further investigation was performed. Serum concentrations of IgG4 were elevated and biopsy of the minor salivary gland revealed a severe infiltration of IgG4-positive plasmacytes. The patient was therefore diagnosed with Mikulicz's disease. Abdominal CT demonstrated diffuse pancreatic swelling, and endoscopic retrograde cholangio-pancreatography revealed stricture of the common bile duct and main pancreatic duct, suggesting the complication of autoimmune pancreatitis. Treatment was commenced with 40 mg/day of prednisolone. This resulted in rapid resolution of the lacrimal and submandibular gland swellings and recovery of salivary gland function. Diffuse swelling of the pancreas and stricture of the common bile duct and main pancreatic duct also improved, and endogenous insulin secretion increased. Both Mikulicz's disease and autoimmune pancreatitis presented with elevated serum IgG4 and infiltration of IgG4-expressing plasma cells into the glandular tissues. We recently proposed the new diagnostic entity of "IgG4-related plasmacytic exocrinopathy"; however, if diabetes mellitus in autoimmune pancreatitis was caused by direct dysfunction of pancreatic cells, we must reconsider this pathogenesis and consider a wider concept including exocrine as well as endocrine glands. This case, in which both types of glands were affected, is therefore of considerable interest.

Pancreatic disease in the autoimmune rheumatic disorders

We report a case of autoimmune pancreatitis without obvious evidence of autoimmunological participation, which responded well to steroid treatment and provided histologic and radiographic evidence for this improvement. A 68-year-old woman presented abdominal fullness, diffuse pancreatic swelling on abdominal computed tomography and ultrasonography, and diffuse narrowing of the main pancreatic duct on endoscopic retrograde pancreatography. Transgastric aspiration needle biopsy of the body of the pancreas performed under endoscopic ultrasonography showed severe atrophy of acinar cells, infiltration of T lymphocytes. She was diagnosed as having autoimmune pancreatitis without obvious evidence of autoimmunological participation. Administration of 30 mg/day of predonisolone was started. Computed tomography showed marked improvement of the diffuse swelling of the pancreas, and endoscopic retrograde pancreatograpy showed amelioration of the narrowing of the main pancreatic duct after the start of treatment. Pancreatic tissue obtained by needle biopsy after the start of treatment with predonisolone revealed marked histologic improvement, including amelioration of the fibrosis, and infiltration of inflammatory lymphocytes, and a substantial increase in the number of pancreatic acinar cells. The present report is the first to demonstrate histologic recovery of autoimmune pancreatitis after steroid therapy.