bleeding disorders (Vitamin K malabsorption) edema (hypoalbuminemia) fatigue flatulence and abdominal distention (bacterial fermentation of unabsorbed food) hypocalcemia metabolic bone disease (Vitamin D deficiency) neurologic manifestation steatorrhea weight loss Causes In humans, the most common causes of EPI are likely related to diabetes (10.5% global prevalence of diabetes, with EPI rates of ranging from 30-50% in Type 1 and 20-30% of Type 2) and IBS-D (7.6-10.8% global prevalence of IBS-D, with EPI rates around 5-6%). Other causes of EPI include acute or chronic pancreatitis and cystic fibrosis, Crohn’s disease, ulcerative colitis, celiac, advanced renal disease, older age, IBD, HIV, alcohol-related liver disease, Sjogren syndrom, tobacco use, and use of soatostatin analogues. EPI can also occur in 10-20% of the general population. Diagnosis The three main tests used in considering a diagnosis of EPI are: fecal elastase test, fecal fat test, and a direct pancreatic function test. The latter is a less used test that assesses exocrine function in the pancreas by inserting a tube into the small intestine to collect pancreatic secretions. The fecal elastase test is a less cumbersome test that has replaced the 72-hour fecal fat test; in the fecal elastase test, pancreatic enzyme replacement therapy (enzyme supplementation, the treatment for EPI) does not have to be stopped for or during fecal elastase testing. Treatment EPI is treated with pancreatic enzyme replacement therapy (PERT) called pancrelipase, which is used to break down fats (via a lipase), proteins (via a protease), and carbohydrates (via amylase) into units that can be digested. Pancrelipase is typically porcine derived in the prescription products although over-the-counter options also exist, including those made with plants and other non-porcine materials. In the US, there are 6 FDA-approved PERT products available on the market as of 2012. Dosing can vary based on the need of the individual. PERT is considered to be safe, effective, and tolerable for people with EPI regardless of the cause of EPI. Other animals Causes and pathogenesis Chronic pancreatitis is the most common cause of EPI in cats. In dogs, where the condition has been deemed common, the usual cause is by pancreatic acinar atrophy, arising as a result of genetic conditions, a blocked pancreatic duct, or prior infection. In dogs, EPI is most common in young German Shepherds, and in Finland Rough Collies, and is inherited. In German Shepherds, the method of inheritance is through an autosomal recessive gene. In these