**6. Clinical presentation**

The most common symptom of chronic pancreatitis is abdominal pain which is present more than 80% of patients. The pain is commonly described as a dull pain in the epigastrium radiating to the back that worsens after meals. The character, pattern and intensity of pain can vary among patients and does not correlate with the extent of pathological/morphologic changes [61]. Patients with alcohol related CP are more likely to experience pain, whereas late-onset CP is stated to be less painful [62]. Nausea, vomiting or both may accompany pain during exacerbations of pain attacks or during episodes of acute pancreatitis. Approximately 70% of adult patients with CP experience at least 1 episode of acute pancreatitis and 50% have recurrent pancreatitis during the clinical course of the disease [63].

Several anatomical complications can occur in CP due to local inflammation or glandular fibrosis symptoms. The formation of pancreatic pseudocysts, which can occur in 10–40% of patients during their lifetime, is one of the most frequent anatomic complications. Pseudocysts can cause gastroduodenal outlet obstruction and/or biliary obstruction, depending on their anatomic location and size [64].

Other anatomical complications are pancreatic stones, pancreatic strictures, biliary strictures and thrombosis of splanchnic vasculature.

One of the complications of CP is exocrine pancreatic insufficiency (EPI). EPI is a condition characterized by insufficient production and/or secretion of pancreatic enzymes for the digestion of nutrients. The predominant symptoms of EPI are related to fat malabsorption. Mild EPI can cause abdominal bloating and discomfort, while severe EPI can cause overt steatorrhea, weight loss and fat-soluble vitamin deficiencies. Generally, EPI does not develop for more than a decade after disease onset, due to the exceptional reserve of the exocrine pancreas and the redundant pathways for digestion of proteins and carbohydrates. Although prevalence of EPI at diagnosis of CP is 10–13%. EPI affects more than 70% of patients with CP throughout their lifespan and is especially frequent in those with proximal obstruction of the pancreatic duct or a history of pancreatic resection [64, 65].

Another complication of CP is metabolic bone disorder which has also been referred to as CP-associated osteopathy. A meta-analysis estimated that the pooled prevalence of osteoporosis was 23.4% and of osteopenia, 39.8% [66]. Additionally, patients with CP have a higher risk of low trauma fractures (vertebrae, hip, and wrist) and the risk of fractures in patients with CP was similar to other gastrointestinal diseases, such as cirrhosis, celiac disease and history of gastrectomy [67].

Diabetes mellitus (DM) is a frequent complication of CP. Prevalence of endocrine insufficiency at diagnosis of CP is 10–33% [4, 8]. A recent systematic review identified a 15% prevalence of new onset diabetes within 36 months and a 33% prevalence within 60 months of CP diagnosis [68]. DM usually occurs several years after the onset of the disease and can eventually affect up to 80% of patients over their lifespan [69]. Due to the high prevalence of CP-DM, annual screening for DM is recommended [70, 71]. In a recent study of participants with CP, DM was more likely to occur in participants who were older, obese, male, black race, or had a family history of DM and factors independently associated with DM included both obesity and the presence of exocrine pancreatic insufficiency [72]. A prolonged period of CP, the absence of pain, cigarette smoking, and an increase in visceral adipose tissue have all been linked to CP-DM [73, 74].
