Summary

Hereditary chronic pancreatitis (HCP), a rare inherited form of pancreatitis is defined as recurrent acute pancreatitis and/or chronic pancreatitis in two first-degree relatives or 3 or more second-degree relatives in 2 or more generations, for which no predisposing factors are identified. HCP is characterized by irreversible damage to both exocrine and endocrine components of the pancreas.

The estimated prevalence of hereditary pancreatitis is approximately 1/300,000 people in Europe ranging from 1/800,000 to 1/330,000. (1/800,000 in Germany, 0.3/100,000 in France and 0.57/100,000 in Denmark).

Onset of HCP is typically early in life. The clinical presentation is highly variable and includes chronic mild to severe abdominal pain associated with exocrine pancreatic insufficiency leading to maldigestion and/or pancreatic endocrine insufficiency (glucose intolerance progressing to diabetes mellitus type 3c). The diseaseis slowly progressive. The risk of developing pancreatic carcinoma (see this term) after the age of 50 is elevated in patients with HCP.

Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) have been found to be associated with chronic pancreatitis (idiopathic and hereditary). Recently, mutations in carboxypeptidase A1 (CPA1) have been found to be associated with HCP and idiopathic chronic pancreatitis with early onset.

Diagnosis of HCP is based on clinical features along with family history of chronic pancreatitis, absence of precipitating factors and a negative workup for known causes of chronic pancreatitis. Imaging (endoscopic ultrasound, endoscopic retrograde cholangiopancreatography (ERCP), Magentic resonance cholangiopancreatography (MRCP)) and biopsy reveal pseudocysts, bile duct and duodenal obstruction. The diagnosis might be substantiated by variants in the genes mentioned above.

Differential diagnoses include other forms of chronic pancreatitis mainly alcoholic chronic pancreatitis, idiopathic chronic pancreatitis , autoimmune pancreatitis (see this term).

Antenatal diagnosis is not encouraged.

Genetic testing should only be performed in carefully selected patients by direct DNA sequencing. Mutation in the PRSS1 gene is transmitted in an autosomal dominant manner with incomplete penetrance.

Mainstays of medical management involve pain control, nutritional support, treatment for diabetes mellitus, and pancreatic enzyme supple¬mentation for exocrine insufficiency. Surgery may be indicated for the management of acute and chronic complications of HCP and includes debridement, drainage, decompression and only very rarely pancreatectomy. Additional risk factors for chronic pancreatitis (smoking, alcohol) should be avoided.

The prognosis of patients with HCP is unpredictable with an increased risk of development of pancreatic carcinoma.

Expert reviewer(s)

• Dr Hans BÖDEKER
• Pr Joachim MÖSSNER
• Dr Jonas ROSENDAHL
• Dr Niels TEICH