LOS ANGELES—The list of purely idiopathic causes of pancreatitis is shrinking, Stephen J. Pandol, M.D., said at the 12th International Symposium on Pancreatic and Biliary Endoscopy sponsored by the Cedars-Sinai Medical Center.
Alcohol use remains the most common etiology, but an enhanced understanding of genetic and autoimmune contributors has demystified the cause of pancreatitis in many patients whose alcohol intake does not appear to put them at risk for the disorder.
No blood markers exist to pinpoint the cause of pancreatitis, and histologic evaluation of the pancreas is difficult, Dr. Pandol noted. Imaging is helpful in diagnosing structural etiologies but is most often nonspecific in terms of identifying a cause.
Alcohol intake directly relates to the relative risk of pancreatitis, and may interact with other factors, such as a hereditary predisposition or virus, to cause pancreatitis. Risk is elevated slightly at 50 g/day, equivalent to four beers, three-quarters of a bottle of wine, or a fifth of a fifth of hard liquor. At three times that intake level, the relative risk of pancreatitis reaches 15.
But automatically attributing pancreatitis to alcohol intake can be a mistake, said Dr. Pandol, professor of medicine at the University of California, Los Angeles.
“You could have gallstones causing pancreatitis in someone who drinks a lot,” he explained.
Certain drugs, cancer, toxins, and vascular abnormalities can trigger acute pancreatitis, and in some cases it can be iatrogenic, occurring after procedures to remove gallstones, for example.
Other potential etiologies that should not be overlooked include:
▸ Gallstones. Calculi are an obvious potential cause of pancreatitis, but they nonetheless are missed, sometimes with catastrophic results. Dr. Pandol said he is familiar with cases in which patients died of acute pancreatitis that was caused by unrecognized gallstones.
“You need good imaging studies to make sure you haven't missed this, because it's very treatable,” he said.
▸ Infectious etiologies. Salmonella can contribute to pancreatitis through a toxic mechanism. Parasitic infections can obstruct the pancreatic duct. In some cases, viruses may be to blame for pancreatitis, although the mechanism remains unclear. In mice, certain strains of coxsackievirus are benign until mice are fed alcohol, after which they develop “severe, rip-roaring, and lethal pancreatitis,” Dr. Pandol said.
▸ Trauma. Even distant trauma should not be ruled out as a possible etiology for pancreatitis. Dr. Pandol recalled a case of a female patient who had been kicked in the abdomen during a sexual assault several years prior to presenting with pancreatitis. Imaging revealed a stricture in the pancreatic duct.
Steering wheel injuries from motor vehicle accidents can rupture the pancreatic duct, he added.
▸ Autoimmune disease. Dr. Pandol isn't certain whether autoimmune pancreatitis is increasingly common, or just better recognized than in the past. Typically, symptoms are subacute, and imaging studies reveal an irregular, narrowed duct.
IgG4 markers are transient but may be seen early in the disease. IgE and autoimmune markers may also be positive, the latter in severe cases. Histology may reveal periductal lymphocytic-plasmacytic inflammation and fibrosis, but features may closely resemble pancreatic cancer. A large amount of tissue may be required at biopsy for a firm diagnosis.
If a patient has preexisting autoimmune disease such as Sjögren's syndrome or systemic lupus erythematosus, autoimmune pancreatitis is a likely diagnosis.
“But if there's a mass, one still has to rule out the possibility of cancer,” Dr. Pandol said.
Autoimmune dysfunction is one of the rare treatable causes of pancreatitis, since it is steroid responsive.
▸ Hereditary causes. Many trypsinogen mutations, mutations in the cystic fibrosis transmembrane regulator genes, and familial hypertriglyceridemia can cause pancreatitis.
Genetic testing—offered by companies such as Ambry Genetics, Irvine, Calif.—can detect relevant abnormalities in trypsin and trypsin inhibitor genes and cystic fibrosis genes, although some families don't want to be tested because of insurance concerns, he noted.