The role of pancreas divisum (PD) as a cause of either acute recurrent or chronic pancreatitis (AR/CP) remains a matter of debate. A recent study suggests that pancreas divisum serves as a cofactor but does not cause pancreatitis independently (Am J Gastroenterol 2012; 107: 311-17).
PD occurs due to failure of fusion of the dorsal and ventral pancreatic buds during gestation. The frequency of PD has been estimated to be between 5-10% of the general population based on large post-mortem studies. There is an increased frequency of PD in patients with idiopathic pancreatitis (12-26%). The referenced study from France examined the frequency of genetic mutations vis-a-vis relationship with PD. PD was determined using MRCP.
Findings–percentage with PD among subgroups:
- 7% of subjects without pancreatic disease, n=45
- 7% of alcohol-associated pancreatitis patients, n=29
- 5% of idiopathic pancreatitis patients, n=40
- 16% of patients with PRSS-1-associated pancreatitis, n=19
- 16% of patients with SPINK-1-associated pancreatitis, n=25
- 47% of patients with CFTR-associated pancreatitis, n=30
The study has several limitations. Overall, the numbers of patients with pancreatitis are fairly low. In addition, these genetic mutations are not typically examined in individuals without pancreatitis. As such, the effect of these mutations with PD still is difficult to know in comparison to a larger population.
- Recurrent pancreatitis and genetic underpinnings (previous blog post)
- -Clin Gastro & Hep 2009; 7:141. Review -case of recurrent pancreatitis -suggests checking ANA, Trig, IgG4 (also TTG)
- – J Pediatr 2008; 152: 106. Acute pancreatitis in young children; 109 cases. systemic dz in 29, drugs in 7, gallstones in 3, annular pancreas in 1, trauma in 7, infections in 16, CF in 2, Idiopathic in 15.
- -NEJM 2006; 354: 2142. Review of acute pancreatitis mgt.
- -Clin Gastro & Hep 2006; 4: 455. Elevated pancreatic enzymes frequently identified in celiac disease.
- -Clin Gastro & Hep 2007; 5: 1347. Celiac is a risk factor for acute & chronic pancreatitis. n=14,239 & 69,381 reference population (Sweden).
- -Pediatrics 2005; 115: e463. CF & pancreatitis
- -JPGN 2003; 37: 5591. Systemic dz 14%, Trauma 14%, drugs 12%, metabolic 6%, structural 5%, infectious 8%, ERCP 6%, Biliary 12%, Familial 3% (but accounted for 20% of episodes) Transplant 8%, idiopathic 8%
- -Clin Perspectives in Gastro 2002; 5: 73. Pancreas divisum
While the absolute number of patients with genetic causes of pancreatitis is small, due to frequent hospitalizations, this remains a significant problem. This month additional information on genetic predisposition for pancreatitis is available (JPGN 2012; 54: 645-50).
Sultan et al (Milwaukee, WI) reviewed the charts of children <18 years with recurrent acute pancreatitis (RAP) and patients with chronic pancreatitis (CP) from 2000-2009. RAP was considered if patient had a minimum of two distinct episodes of acute pancreatitis. Acute pancreatitis was considered the diagnosis if patient had typical symptoms associated with 3-fold elevation of amylase or lipase or imaging changes consistent with acute pancreatitis. CP was defined as a minimum of 2 episodes of acute pancreatitis associated with pancreatic duct abnormalities or pancreatic insufficiency.
Among this cohort of 29 children, 23 (79%) had mutations which have been associated with genetic pancreatitis (GP). Family history was positive in only five patients.
- CFTR mutation in 14 (48%): two had homozygous mutations, six heterozygous, and four had 5 T variants. The importance of a single CFTR mutation in contributing towards pancreatitis is unclear. However, the Wisconsin population has a carrier frequency of 1:32; the striking difference in frequency indicates that even a single mutation may be important in the pathogenesis of RAP.
- SPINK1 (serine protease inhibitor Kazal type 1) in 8 (27%). SPINK1 mutations occur in 1-3% of the general population. It is often a modifying factor rather than an isolated causal factor in the development of RAP. Four of the patients with SPINK1 mutations also had a CFTR mutation.
- PRSS1 (cationic trypsinogen gene) in 7 (24%). Individuals with these mutations are considered to have hereditary pancreatitis, an autosomal disease with incomplete penetrance.
- Only one patient was tested for chymotrypsin C gene (CTRC) –tested negative.
Seven patients with RAP did not undergo genetic testing & were excluded from the study. These patients had other known causes of RAP: 3 had gallstones, 2 had pancreas divisum, 1 had a metabolic disorder, and 1 had a medication-induced pancreatitis. The authors note, however, that patients with pancreas divisum have had genetic mutations identified in other studies.
- www.uni-leipzig.de/pancreasmutation. This link will take you to the hereditary pancreatitis database where you can search for the specific mutation you identified and find articles dealing with a variety of aspects of that particular mutation.
- 2011 Naspghan Postgraduate Course:
-1st bout, check U/S, trig
-if 2nd bout, suggested to check MRI, genetics (SPINK1, PRSS1, CFTR), sweat test, fecal elastase, possibly IgG4/ANA
- -Gastroenterology 2006; 131: 1844. Mouse model w R122H Trypsiongen expression.
- -Whitcomb DC. Gut 2004; 53: 1710-17. test for PRSS1 (cationic trypsinogen), SPINK1 (Serine protease inhibitor, Kazal Type 1), and CFTR gene.
- -JPGN 2002; 34: 1A pg 444. n=108 with hereditary or idiopathic pancreatitis. (28% had + fhx) 12 c PRSS1 mutation, 24 c SPINK1 (21 s fhx); 22 had + CFTR mutation.
-Pancreatology 2001; 1: 405-415. Consensus guidelines for testing for H. Pancreatitis. PRSS1 gene -cationic trypsinogen
- David Whitcomb’s laboratory at the University of Pittsburgh. The test is commercially available there. Their web site for the forms is:
- -JPGN 2011; 52: 262. Review.
- -J Pediatrics 2011; 158: 612. Acute pancreatitis can result in diabetes.
- -Clin Gastro & Hep 2010; 8: 410-416, 417. REVIEW of acute pancreatitis. Rec NJ generally over TPN.
- -Clin Gastro Hep 2010; 8: xxii. Anomalous pancreatobiliary jxn as a cause.
- -JPGN 2009; 49: 137. Pancreatitis assoc w celiac
- -Clin Gastro & Hep 2009; 7: 702. Harmless Acute pancreatitis score. Nonsevere when NL hgb, NL creatitine, and no rebound tenderness/guarding
- -Alim Pharm Ther 2008; 28: 777-781. Use of a low fat diet helped shorten hospital stay among adult pts with acute pancreatitis.
- -Clin Gastro & Hep 2008; 6: 1070, 1077. Fluids and imaging in acute pancreatitis. With imaging, CT probably best.
- – J Pediatrics 2008; 152: 106. Acute pancreatitis in young children
Related blog entry:
Indomethacin to prevent post-ERCP pancreatitis