3.2　Risk Factors

The risk factors associated with pediatric CP are listed in Table 11.7.While ARP and CP in adults are most often secondary to gallstones or excessive alcohol usage，（Cote et al.2011；Munirajet al.2014；Yadav et al.2009）the risk factors involved in disease progression in children are poorly delineated（Lucidi et al.2011；Morinville et al.2012）.In contrast to the adult population，alcohol use，smoking and other environmental factors are uncommon in children with CP（Schwarzenberg et al.2015）.Since the identification of PRSS1 as a cause of hereditary pancreatitis，single center-studies with small cohorts reported that children with ARP or CP often have mutations in the cationic trypsinogen（PRSS1），cystic fibrosis transmembrane generator（CFTR），serine protease inhibitor Kazal type I（SPINK1），chymotrypsin-C（CTRC）and carboxypeptidase 1（CPA1）genes（Lucidi et al.2011；Sanchez-Ramirez et al.2007；Schnur et al.2014；Sobczynska-Tomaszewska et al.2006；van Geenen et al.2011；Werlin et al.2015；Witt 2001；Witt et al.2013）.Indeed，in the largest pediatric CP population reported by INSPPIRE，two third of children had at least one mutation identified in PRSS1，SPINK1，CFTR，or CTRC（Schwarzenberg et al.2015）.In the last decade，more genetic associations have been reported with CP including claudin 2（CLDN2），carboxylesterlipase（CEL）and CEL-Hybrid（CEL-HYB）（Derikx et al.2015；Fjeld et al.2015；Ragvin et al.2013；Witt et al.2013）.A strong association with the CPA1 gene and early childhood pancreatitis（less than ten years of age）highlights the importance of genetic influences at an early age（Witt et al.2013）.While additional pediatric studies have reported varying proportions of genetic associations with ARP or CP，the impact of genetic mutations on natural history and disease outcome should be studied on well-defined and prospectively followed cohorts.

Table 11.7　Risk factors of chronic pancreatitis in children(https://www.daowen.com)

Environmental risk factors（i.e.medications，alcohol，smoking，chronic renal failure，hypercalcemia）are uncommon in pediatric CP（0-4%）（Oracz et al.2015；Schwarzenberg et al.2015）.It is notknown whether obstructive factors and specifically pancreas divisum are sufficient to cause CP in children.In the INSPPIRE cohort，pancreas divisum was present in～20%of children with CP（Schwarzenberg et al.2015），which is higher than what has been reported in subjects without pancreatic disease（7%）（Rebours et al.2009）.Future studies are needed whether pancreas divisum has an impact on pediatric pancreatic disease progression and development of CP.Autoimmune pancreatitis（AIP）is scarce in the pediatric population with only a few centers publishing cases or case series（Friedlander et al.2012；Fujii et al.2013；Zen et al.2014）.Most cases are type 2 AIP and the response to steroids in general is good.