Exocrine pancreatic insufficiency

EPI is a condition characterized by the inadequate production or secretion of digestive enzymes by the pancreas, leading to malabsorption and nutritional deficiencies.

Progressive structural and functional alterations in the pancreatic acinar and ductal compartments, such as in chronic inflammation, fibrosis, and ductal obstruction, compromise the synthesis, processing, and delivery of pancreatic digestive enzymes into the duodenum. These pathologic changes disrupt the coordinated release of lipolytic, proteolytic, and amylolytic enzymes, impairing the normal hydrolysis of dietary macronutrients. Over time, the enzymatic deficiency leads to a profound disturbance in nutrient absorption, resulting in weight loss and micronutrient deficiencies.

The prevalence of EPI varies by the underlying condition and its severity, ranging from 20-90% in chronic pancreatitis, 27-35% after acute pancreatitis, 70% in pancreatic cancer, 75-90% in cystic fibrosis, 10-100% after pancreatic surgery, and 9-67% after upper gastrointestinal surgery. Low fecal elastase-1 levels have been reported in 21.7% of individuals aged > 60 years and 11.5% of individuals aged 50-75 years.

Common causes of exocrine pancratic insuficiency include chronic pancreatitis, post-acute pancreatitis, pancreatic or ampullary cancer, cystic fibrosis and CFTR-related disorders, and pancreatic surgery. Other conditions that are associated with exocrine pancratic insuficiency include autoimmune pancreatitis, celiac disease, IBD, short bowel syndrome, gastrinoma, Sjögren's disease, hemochromatosis, upper gastrointestinal surgery, immune-checkpoint inhibitor and TKI therapy, somatostatin analogs, and rare inherited disorders, such as Shwachman-Bodian-Diamond syndrome, Johanson-Blizzard syndrome, Pearson syndrome, and Shteyer syndrome. Additionally, patients with CKD, congestive HF, alcohol use disorder, and the elderly have an increased risk of EPI.

Clinical manifestations of EPI typically evolve gradually as the capacity for adequate digestive enzyme delivery declines, often remaining subtle until significant maldigestion occurs. Symptims include steatorrhea, characterized by greasy, foul-smelling stools, abdominal pain, bloating, flatulence, weight loss, muscle wasting, and deficiencies in fat-soluble vitamins (A, D, E, K), which may present as night blindness, osteopenia, coagulopathy, or neurological symptoms. Vitamin B12 deficiency may also occur as a result of reduced intestinal pH, impairing the transfer of vitamin B12 from R protein to intrinsic factor. In advanced stages, ongoing nutrient deficits lead to further metabolic derangements, deterioration of general health, and diminished QoL.