Cystic fibrosis and exocrine pancreatic insufficiency

Cystic fibrosis (CF) is a genetic disease affecting many organs including the gastrointestinal tract. While the pulmonary damage is the most life threatening, the pancreas is one of the first and most affected organs by CF. Mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene results in a reduced volume of pancreatic juice and hyperconcentration of macromolecules leading to precipitation in the duct lumina, causing obstruction and damage. The clinical presentation of individual cases depends on a combination of different CFTR mutations, potential presence of modifier genes mutations, and environmental factors. The CFTR mutations are historically divided into 5 classes - severe mutations (classes I-III) and mild mutations (classes IV-V). The CFTR functional status depends on the combined effects of both CFTR allels and the severity of the phenotype depends on the milder mutation. The majority of CF patients exhibit exocrine pancreatic insufficiency in early childhood because functional acinar tissue has been lost in utero or soon after birth. These patients rarely suffer from pancreatic complications such as recurrent acute pancreatitis and/or chronic pancreatitis which, on contrary, can occur in the minority of patients who possess residual pancreatic exocrine function. CFTR mutations are found more frequently in idiopathic and alcoholic chronic pancreatitis but the data is conflicting. A combination with SPINK-1 mutations can be found in idiopathic chronic pancreatitis group, as well as presence of environmental factors. Malnutrition is directly related to worse prognosis of CF patients and delivery of active digestive enzymes is a cornerstone of the treatment with acid supression and vitamins supplementation playing an important additional role.