Autoimmune pancreatitis: an underdiagnosed autoimmune disease with clinical, imaging and serological features.

Since Sarles et al. [Sarles H, Sarles JC, Muratore R, Guien C. Chronic inflammatory sclerosis of the pancreas-an autonomous pancreatic disease? Am J Dig Dis 1961; 6: 688-698.] reported a case of pancreatitis associated with hypergammaglobulinemia, many cases have been described, which led to the current concept of "autoimmune pancreatitis (AIP)". Lymphoplasmacytic infiltration and fibrosis on histology together with elevated IgG levels or the presence of autoantibodies on laboratory examinations supported the concept of AIP. In recent years, based on histological and immunohistochemical examination of various organs of patients with AIP, a novel clinicopathological entity, IgG4-related slerosing disease, has been proposed. AIP is a systemic disease that is characterized by dense infiltration of IgG4-positive plasma cells and T lymphocytes in various organs. Clinical manifestations are related with pancreas dysfunction but other organs may be affected such as bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung and prostate. Increased serum IgG4 levels, the presence of several autoantibodies such as anti-carbonic anhydrase II antibodies (ACA-II), immunostaining IgG4 positive in pancreas tissue and a very good response to steroid therapy are useful for the diagnosis of AIP that can mimic pancreatic cancer.

Hereditary pancreatitis: clinical features and inheritance characteristics of the R122C mutation in the cationic trypsinogen gene (PRSS1) in six Spanish families.

CONTEXT: Hereditary pancreatitis is an autosomal dominant disease which is caused by mutations in the PRSS1 gene. OBJECTIVE: The aim of our study was to describe the penetrance and phenotype-genotype correlations of the c.346C>T (p.R122C) mutation. DESIGN: Case series descriptive study. PATIENTS: Forty-one members of six families from whom DNA samples were analyzed. MAIN OUTCOME MEASURES: In subjects with R122C mutation symptoms, pancreatic calcifications, main pancreatic duct changes, diabetes, steatorrhea, pancreatic cancer and surgery were recorded. RESULTS: The R122C mutation was detected in 22 of the 41 family members studied, and 7 men and 2 women developed pancreatic disease, resulting in a penetrance of 40.9%. One out of the 9 patients was excluded because she died before the mutation was detected. The mean age at symptom onset was 23.5 years (range: 4-51 years). Abdominal pain was present in 6 (75.0%) of the 8 patients with the R122C mutation who developed pancreatic disease. Calcifications had developed in 5 (62.5%) at a mean age of 35.8 years (range: 14-56 years). Five (62.5%) developed changes in the pancreatic ducts at a mean age of 44.2 years (range: 19-65 years). Two patients (25.0%) developed steatorrhea during the follow-up at 26 and 35 years of disease progression. Diabetes developed in five patients (62.5%) at a mean age of 41.4 years old (range: 22-53 years). Three of the patients analyzed (37.5%) developed pancreatic cancer at 59 years of age, 63 years of age and 70 years of age. CONCLUSIONS: Penetrance of the R122C mutation is lower than that described for the R122H and N29I mutations, and there is a tendency toward a predominance of males with the R122C mutation who developed the phenotype of pancreatitis.

Pancreatic fibrosis in rats and its response to antioxidant treatment.

CONTEXT: Oxidative stress plays a role in the development of pancreatic fibrosis. OBJECTIVES: In the present study, we hypothesized that the administration of an antioxidant complex could ameliorate cerulein and cyclosporin A pancreatic fibrosis, assessed by changes in oxidative stress and a histopathological study in an experimental rat model. ANIMALS: Four groups of ten rats each. In Group A, the rats served as controls and were treated with intraperitoneal saline solution. In Group B, six courses of cerulein pancreatitis were induced at weekly intervals. In Group C, the rats received cyclosporin A the day before and the day on which pancreatitis was induced in Group B. In Group D, the rats were treated as in Group C but also received antioxidants. All rats were sacrificed at the seventh week. MAIN OUTCOME MEASURES: The presence of fibrosis was evaluated according to a scoring system. Glutathione peroxidase was utilized as an indicator of oxidative stress and total antioxidant status as an indicator of total antioxidant tissue capacity. RESULTS: The rats in Groups B and C showed more pancreatic fibrosis than those in Groups A and D (90%, 70%, 0%, and 20%, respectively). The glutathione peroxidase increased in Group B (455+/-196 mU/g protein) and Group C (243+/-206 mU/g protein) with respect to those in Group A (137+/-80 mU/g protein) and Group D (135+/-105 mU/g protein). Total antioxidant status was significantly higher in Groups B (1.41+/-0.96 mmol/g protein) and D (1.28+/-0.09 mmol/g protein) with respect to Groups A (0.10+/-0.06 mmol/g protein) and C (0.15+/-0.09 mmoL/g protein). CONCLUSION: The administration of cerulein and cyclosporin A caused fibrosis, whereas antioxidant administration showed preventive effects regarding cerulein and cyclosporin A-induced pancreatic fibrosis.

[Screening of celiac disease in first-degree relatives]. / Cribado de la enfermedad celíaca en familiares de primer grado.

BACKGROUND AND OBJECTIVE: Our aim was to analyze the prevalence of celiac disease (CD) in first-degree relatives of patients diagnosed with this disorder in Cantabria (Northern Spain). SUBJECTS AND METHOD: A questionnaire was administered and a complete biologic study was performed in 184 relatives. When serum CD-related antibodies were detected, relatives were asked to undergo a jejunal biopsy to confirm the diagnosis. RESULTS: Thirteen relatives had autoantibodies yet only 4 were diagnosed with CD. The biopsy was suggestive of CD in 3 relatives who underwent it. A further relative was diagnosed with CD by the clinical and serological response to a gluten-free diet. CONCLUSIONS: The prevalence found in our study is high enough so that we recommend the screening of autoantibodies, especially anti-gliadin and anti-transglutaminase antibodies, in this risk-population of celiac disease.