Pancreatitis

Acute pancreatitis presents with sudden-onset epigastric pain, often radiating to the back, accompanied by serum amylase or lipase elevated to more than three times the upper limit of normal and characteristic findings of pancreatic inflammation on cross-sectional imaging. Recurrent acute pancreatitis is defined by two or more documented episodes separated by at least three months, whereas chronic pancreatitis is a fibro-inflammatory syndrome characterised by pancreatic atrophy, parenchymal fibrosis, ductal distortion and calcifications, exocrine insufficiency with steatorrhoea, weight loss and fat-soluble vitamin deficiency, and pancreatogenic diabetes mellitus. Long-standing disease additionally confers an increased risk of pancreatic ductal adenocarcinoma. Onset spans childhood through adulthood; paediatric cases occur with a median diagnosis age of seven years in PRSS1-related hereditary pancreatitis cohorts, and early-onset disease (under 35 years) is particularly suggestive of an underlying genetic aetiology. Clinical presentation may be isolated (nonsyndromic hereditary pancreatitis) or part of a broader multisystem disorder (syndromic forms), in which pancreatitis arises alongside additional organ involvement.

Acute pancreatitis shows an incidence of approximately 10-50 cases per 100,000 individuals per year, while chronic pancreatitis is less common, with reported incidence rates of 5-12 per 100,000 individuals per year. Prevalence estimates for chronic pancreatitis vary widely across regions, generally ranging from 40-120 cases per 100,000 population, reflecting geographic differences in risk factors, diagnostic practices, and healthcare access.

Several genes are currently included in diagnostic gene panels for pancreatitis. Most paediatric cases are associated with germline pathogenic variants in PRSS1, causing hereditary pancreatitis through gain-of-function effects on trypsinogen, while SPINK1-related pancreatitis results from impaired trypsin inhibition. Other genes implicated in pancreatitis include CTRC, which encodes chymotrypsin C, and CFTR, which encodes the transmembrane conductance regulator.

The genetic conditions associated with pancreatitis follow heterogeneous inheritance patterns, including autosomal dominant, autosomal recessive, and polygenic forms. Autosomal dominant inheritance is most observed in PRSS1-related hereditary pancreatitis, while recessive forms involve biallelic variants in SPINK1 or CFTR. Notably, both biallelic and heterozygous CFTR variants can increase the risk of pancreatitis. In addition, some forms display complex polygenic or multifactorial inheritance combining genetic and environmental risk factors.