History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include alcohol, smoking, and family history.

abdominal pain

Occurs in more than 80% of people at time of diagnosis.[11] Pain is epigastric, dull, radiating to the back, diminished by sitting forwards, worse approximately 30 minutes post-prandially.

Ammann classifies pancreatitis-related abdominal pain into short episodes/relapsing (type A), and constant/prolonged episodes of pain (type B); the latter is more common in alcoholic and early-onset idiopathic chronic pancreatitis.[124]

The decrease or resolution of pain correlates with development of pancreatic calcifications and pancreatic endocrine and/or exocrine insufficiency in some studies, but may vary.[11][125][126][127]

steatorrhoea

Overall incidence is between 8% and 22% at the time of diagnosis.[11] Occurs before azotorrhoea (malabsorption of dietary protein).

Is due to injury, atrophy, and loss of pancreatic exocrine tissue due to inflammation and fibrosis of the gland.

Must exclude mineral oil ingestion.

uncommon

jaundice

Overall incidence around 10%.[90] Due to common bile duct compression. Usually preceded by alkaline phosphatase elevation without jaundice or other symptoms.

Pancreatic cancer should be considered.

Other diagnostic factors

common

weight loss and malnutrition

Commonly develops because of fear of food (due to pain), malabsorption, and/or uncontrolled diabetes mellitus. Micro-nutrient deficiencies may also develop. The prevalence of fat-soluble vitamin deficiencies is variable and is reported to be 14.5% for vitamin A, 24.2% for vitamin E, and as high as 53% for vitamin D.[95][96] These deficits can potentially lead to long-term health problems, including visual deficits, neurological defects, and poor bone health.

Pancreatic cancer should be considered.

diabetes mellitus/glucose intolerance

Glucose intolerance occurs early due to insulin resistance, and diabetes mellitus occurs late due to insulinopenia.[92] The overall prevalence of hyperglycemia is 47%. The incidence of diabetes mellitus ranges from 0% to 22% at onset of symptoms, and more than 80% after 25 years.[11][93]

nausea and vomiting

Non-specific. Due to short- and long-term complications of chronic pancreatitis.

May result from altered post-prandial gastric myoelectrical activity and is exacerbated by opioid analgesics; however, it remains controversial whether patients with chronic pancreatitis have delayed, normal, or rapid gastric emptying.[101][102][103][104][105]

bloating and/or excessive flatulence

Non-specific symptom of pancreatic exocrine insufficiency.[84]

uncommon

skin nodules

Pancreatic lipase may leak into the circulation and cause fat necrosis at non-pancreatic sites. This results in painful and painless skin nodules on the extremities, associated with fever and polyarthritis.[106][107]

Around 5% of patients with pancreatitis develop intra-medullary fat necrosis, but this does not commonly cause symptoms.[108]

painful joints

Occurs in at least two conditions associated with pancreatic disease: metastatic fat necrosis; immunoglobulin G4-related autoimmune pancreatitis, associated with rheumatoid arthritis with or without secondary amyloidosis.[107][109]

low-trauma fracture

Prevalence of 4.8%.[98] Related to decreased bone mineral density, malnutrition, and increased systemic inflammation.[97] Fracture risk is greater if alcohol is an underlying risk factor for chronic pancreatitis and the patient has cirrhosis.[100]

abdominal distension

Aetiology related to enlarged pseudocyst, pancreatic cancer, pancreatic ascites due to juice leaking from a ruptured duct or pseudocyst, or duodenal fibrosis and obstruction leading to gastric distension.

shortness of breath

Due to pleural effusion, secondary to juice leaking from a ruptured duct or pseudocyst and tracking to pleural space.

Risk factors

strong

alcohol

Worldwide, alcohol is the major risk factor for chronic pancreatitis (70% to 80%).[23][48][49]​​

Co-factors required to induce alcoholic pancreatitis include anatomical, environmental, and/or genetic factors, as few people with chronic alcohol dependence develop the disease (no more than 10%, and likely <3%).[31][32][33]

One meta-analysis identified alcohol (along with smoking and male sex) as risk factors for chronic pancreatitis in those with single or multiple attacks of pancreatitis.[20]

smoking

Cigarette smoking inhibits exocrine pancreatic secretion of bicarbonate and fluid and is an independent and dose-dependent risk factor for developing chronic pancreatitis.[23][25][50][51]​​​[52][53][54][55]​​​​​​ Smoking is associated with earlier onset and accelerated progression of alcoholic chronic pancreatitis and senile chronic pancreatitis, but not juvenile chronic pancreatitis.[10][34][53]

Smoking is an independent predictor for progression from non-gallstone-related acute pancreatitis to chronic pancreatitis.[56] One meta-analysis identified smoking (along with alcohol and male sex) as a risk factor for chronic pancreatitis in those with single or multiple attacks of pancreatitis.[20] Calcifications occur more frequently in smokers and correlate with the amount and duration of drinking.[29][57][58]

family history

Three major groups of mutations occur in chronic pancreatitis: cationic trypsinogen or serine protease I (PRSS1); serine protease inhibitor, Kazal type 1 (SPINK1); and the cystic fibrosis transmembrane conductance regulator (CFTR).

Between 52% and 81% of patients with hereditary pancreatitis have PRSS1 gene mutations, around 50% of patients with early-onset idiopathic chronic pancreatitis have SPINK1 or CFTR mutations, and 20% to 55% of patients with tropical pancreatitis have SPINK1 gene mutations.[23][59][60]​​

Mutations of the PRSS1, SPINK1, and CFTR genes are associated with forms of chronic pancreatitis and recurrent acute pancreatitis but not with single episodes of human acute pancreatitis.[61][62][63]

Less commonly, idiopathic chronic pancreatitis is associated with mutations in the chymotrypsinogen C gene, calcium-sensing receptor gene, X-linked claudin 2 gene, carboxypeptidase A1, fucosyltransferase 2 non-secretor status, ABO blood group type B, an unidentified gene mutation, and potentially epigenetic mechanisms or a non-genetic alteration in protein function.[64][65][66][67][68][69][70] For example, some patients have a variant cystic fibrosis phenotype without CFTR gene mutations, including those with chronic pancreatitis from known causes.[71][72][73]

Genetic counselling is strongly recommended for patients with a compelling personal or family history and/or positive genetic testing. The clinical implications of the latter should be interpreted carefully because the classification of variants (not pathogenic; probably not pathogenic; uncertain; probably pathogenic; definitely pathogenic) often changes in complex diseases, leading to re-classification (up or down) over the course of years.[74][75][76]

coeliac disease

Patients with coeliac disease have an increased risk of developing any form of pancreatitis, particularly idiopathic recurrent acute pancreatitis or chronic pancreatitis.[77][78][79]

weak

psoriasis

Patients with psoriasis may have an increased risk of developing chronic pancreatitis, based on a preliminary, population-based study from Taiwan.[80]

high-fat, high-protein diet

May increase the risk of chronic pancreatitis.[29] Further research is required.

tropical geography

Environmental and genetic risk may increase the risk of specific types of chronic pancreatitis. For example, tropical pancreatitis is prevalent in specific geographical regions and associated with serine protease inhibitor, Kazal type 1 (SPINK1) gene mutations.[81]

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