**4.1 Etiology**

*Pancreatitis*

disease [18].

fibrosis).

mutations and IgG4.

reducing intraductal hypertension.

**3.3 Treatment**

*3.1.4 Autoimmune disorders*

responsive to corticosteroid therapy.

**3.2 Clinical features and diagnosis**

Autoimmune pancreatitis is an increasingly recognized disease entity associated with hypergammaglobulinemia. High serum levels of IgG4 are suggestive of AIP in adults while just 22% of pediatric patients have immunoglobulin levels above the upper limits of normal [19]. AIP can be classified into two types: type one lymphoplasmacytic sclerosing pancreatitis and type two idiopathic duct-centric pancreatitis. The latter form seems to be more frequent in children and it is associated with inflammatory bowel syndrome. Anyway this distinctive type of pancreatitis is

ARP can be defined as two or more episodes of acute pancreatitis occurring with complete resolution of symptoms in between (>1 month between two episodes) or normalization of pancreatic enzymes serum levels in the time interval, with not detected radiological signs of chronic pancreatitis. ARP should be considered in the diagnostic process of children with a positive anamnesis for recurrent gastroenteritis with vomiting, epigastric pain, or irritable bowel syndrome. An early identification of the underlying etiology may lead to a complete resolution of the

The most common risk factors in childhood are genetic mutations so gene testing is mandatory and a chloride sweat test is helpful to diagnose a CF (cystic

The patient's anamnesis and standard laboratory tests, trans-abdominal ultrasound, MRCP, and CT scan can easily detect the causes of recurrent pancreatitis in about 70% of cases. The remaining 30% of patients should have further investigations such as genetic testing, MRCP (magnetic resonance cholangiopancreatography), that provides the potential to delineate ductal anatomy without the risks of contrast injection, EUS (Endoscopic UltraSonography) and ERCP, that represents the most accurate imaging to define the pancreas anatomy. Genetic and autoimmune pancreatitis can be diagnosed by sequencing CFTR or SPINK1/PRSS1 gene

Therapeutic approach to recurrent pancreatitis associated with pancreas divisum is based on endoscopic and surgical procedures. Both strategies are effective in 70–90% so the former therapy is preferred. Surgery may include accessory duct sphincteroplasty alone or in combination with major sphincteroplasty and septoplasty. Patients with distal ductal obstruction or ductal ectasia may take advantage from pancreaticojejunostomy [20]. Annular pancreas is another congenital aletaration of the pancreatic ductal system and surgical resection represents the preferential treatment. Recurrent pancreatitis associated with the CFTR-gene mutation of hereditary pancreatitis may be prevented by endoscopic pancreatic sphincterotomy

Furthermore, in last years, many efforts have been made to identify a novel therapy for lipoprotein lipase deficiency (LPLD), a genetic disease causing chylomicronemia and an increased risk for developing acute and recurrent pancreatitis. Thus alipogene tiparvovec (Glybera) gene therapy has definitely proven to be effec-

tive in reducing frequency and severity of pancreatitis events [21].

**76**

As mentioned above genetic mutations are the most common causative factors for pancreatitis in children despite other risk factors may be brought into play as the TIGAR-O classification system well explained and categorized according to toxic-metabolic causes, idiopathic, genetic, autoimmune and obstructive chronic pancreatitis [23]. Within the last years, multiple studies have reported rates of genetic mutations associated with pancreatitis, involving CFTR, SPINK1 and PRSS1 genes, from 36 to 73%. So future perspectives will certainly focus on a personalized medicine approach in order to define a more specific and targeted treatment. Cationic trypsinogen PRSS1 is the gene most frequently involved in the evolution to the end stage of chronic pancreatitis. Near to 80% of individuals with either the R122H or N29I gain of function mutation develop at least one episode of acute pancreatitis and half of clinically affected individuals with either the R122H or N29I mutation will evolve to chronic pancreatitis.

Moreover pancreas divisum represents an obstructive cofactor in the development of chronic involutional changes of the pancreatic gland.
