Autoimmunity and chronic pancreatitis: a concealed relationship.

Chronic pancreatitis is an inflammatory disease well known for its epidemiological and clinical aspects, but still obscure as to its aetiology and pathogenesis [1]. Alcohol has been identified to be the cause of the disease, since the largest number of patients suffering from chronic pancreatitis were found to have consumed large quantities of wine or spirits over a long period of time [2, 3, 4]. The French school furnished the mechanism by which alcohol caused injury to the pancreas, namely, the lithostathine hypothesis [5]. From this point of view, chronic pancreatitis should be a calcifying-calcified disease caused by alcohol-induced and/or genetically-induced alterations of lithostatine, a protein able to solubilize the calcium present in the pancreatic juice. Unfortunately, there are no experimental models for this hypothesis, and all attempts failed to reproduce chronic pancreatitic-like lesions in alcoholic fed animals [6]. Furthermore, there is clinical [7] and biochemical evidence [8] that does not support the lithostatine hypothesis. In the late 1990s, new concepts emerged regarding the pathogenesis of chronic pancreatitis. First, chronic pancreatitis is not a single disease but probably many different diseases, with different pathogenesis and with many different epidemiological, clinical and instrumental aspects [9]. In the last 20 years, many clinical entities involving the pancreas have been identified histologically or instrumentally, such as obstructive pancreatitis [9], pancreatitis associated with cystic dystrophy of the duodenal wall [10, 11, 12, 13], pancreatitis associated with mutations of the cystic fibrosis trans-membrane conductance regulator (CFTR) gene [14, 15, 16] and hereditary pancreatitis [17, 18, 19]. But the newest “radical” concept in the pancreatic field is the possibility that acute pancreatitis may evolve into chronic pancreatitis [20]. This was especially demonstrated in inherited pancreatitis and in pancreatitis associated with mutations of the CFTR gene, but some Authors postulated this evolution in all patients suffering from chronic pancreatitis [20]. The main consequence of this hypothesis is not to use the terms acute recurrent and chronic pancreatitis, but to introduce the more general term “pancreatitis” for patients suffering from recurrent episodes of pancreatitis. The second consequence is the identification of the cause of acute pancreatitis, because, if we know the cause, we may be able to remove it and stop the progression of the inflammatory process in the pancreas. Therefore, we strongly believe that chronic pancreatitis is an heterogeneous disease, with different mechanisms of damage and we would like to introduce the term “inflammatory pancreatic diseases” to identify the inflammatory diseases involving the pancreas.