Pancreatitis in Childhood
Mark E. Lowe, MD, PhDDivision of Pediatric GastroenterologyChildren’s Hospital of Pittsburgh and the University of Pittsburgh Medical Center3705 Fifth AvenuePittsburgh, PA 15213Tel: 412-692-5180FAX: [email protected]
Abstract
Inflammatory disease of the pancreas fall into two major classifications, acute and
chronic. Acute pancreatitis is a reversible process whereas chronic pancreatitis produces
irreversible changes in the architecture and function of the pancreas. The recent finding
that mutations in the gene encoding cationic trypsinogen associate with hereditary
pancreatitis, the identification of genes that increase the risk for developing chronic
pancreatitis and advances in cell biology have contributed greatly to our understanding of
the molecular mechanisms leading to pancreatitis. Although pancreatitis is less common
in children than in adults, it still occurs with regularity and should be considered in any
child with acute or chronic abdominal pain. The major differences between pancreatitis
in children and adults lie in the etiologies and outcome of acute pancreatitis and in the
etiology of chronic pancreatitis. The treatment of acute and chronic pancreatitis is similar
in all ages.
Introduction
Knowledge about the pathophysiology of pancreatitis and the development of effective
therapy has lagged behind the progress made in many other important diseases. Over the
years, many factors have contributed to this disparity including the inaccessible location
of the pancreas, reluctance to employ invasive diagnostic methods, and a paucity of
human studies utilizing modern molecular methods. In recent years, the application of
advances in cell biology and genetics and in imaging techniques in studies of pancreatitis
has provided critical information about the pathophysiology, genetics and anatomy of
pancreatitis. Additionally, several new single and multicenter studies have improved our
understanding of the etiology and clinical course of pancreatitis in childhood. Taken
together within the context of pancreatic physiology, these advances provide the basis for
future diagnostic methods, treatment and prevention of pancreatic inflammatory disease.
Overview of Pancreatitis
Inflammatory disorders of the pancreas fall into two classifications, acute pancreatitis and
chronic pancreatitis. Acute pancreatitis is defined clinically as the sudden onset of
abdominal pain associated with a rise of pancreatic digestive enzymes in the serum or
urine with or without radiographic changes in the pancreas. It is a reversible process with
no lasting effects on pancreatic histology or function. In contrast, chronic pancreatitis is
the sequelae of long-standing destructive, inflammatory injury to the pancreas resulting in
fibrosis, loss of normal pancreatic cells, and chronic inflammatory infiltrates. Clinical
diagnosis depends on identifying the typical histological and morphological changes in
the pancreas and, eventually, loss of pancreatic function. Thus, acute pancreatitis is an
event and chronic pancreatitis is a process.
Prevalence of Acute Pancreatitis
Acute pancreatitis is not common in children. Early published series reported 2 to 9
cases per year. More recent studies show an increasing number of cases in large teaching
hospitals where a 100 or more patients with acute pancreatitis may be seen in a year[1-
3●●]. The reason for this observation is not clear, but neither referral bias nor improved
diagnosis appears to explain the change[1●●].
Pathophysiology of Acute Pancreatitis
Three phases characterize the pathophysiology of acute pancreatitis[4●]. First, a number
of events can initiate the onset of acute pancreatitis. Next, a series of intra-acinar cell
events produce cellular injury and local tissue damage. Finally, acinar cell damage
induces a variety of local and systemic responses including the production of cytokines,
the generation of reactive oxygen species and abnormalities in the local circulation. The
severity of the clinical course is governed by the magnitude of these events and on the
induction of a systemic inflammatory response.
Triggering Events or Etiology of Acute Pancreatitis
A number of factors can trigger an attack of acute pancreatitis[5] (Table 1). Acute
pancreatitis is often found in association with systemic illnesses and after organ
transplant[1●●, 3●●]. The mechanism for pancreatitis in these illnesses is unknown and
likely multifactorial. Obstructive causes, which are common in adults, account for a
portion of episodes in children. Gallstones may be more prevalent in children than
previously thought. In previous studies gallstones were frequently lumped with other
obstructive causes and the incidence is impossible to discern. One recent report from
Korea found gallstones in 29% of cases[6]. Structural abnormalities, such as pancreas
divisum, choledochal cysts, and gastric or duodenal duplication cysts, and periampullary
lesions, such as Crohn disease or duodenal ulcer, can also obstruct pancreatic flow and
cause acute pancreatitis in children. Trauma remains an important etiology of acute
pancreatitis in childhood especially in younger children. A variety of medications have
been associated with acute pancreatitis[1●●, 3●●]. The anticonvulsant valproic acid is
the most common medication reported in most series, but other anticonvulsants and
chemotherapeutic agents have also been associated with acute pancreatitis. The
mechanism for drug-induced pancreatitis is speculative and most theories center on
disruption of cellular metabolism by the drugs or their metabolites.
Acinar Cell Events in Acute Pancreatitis
Current explanations for the early acinar cell events in acute pancreatitis center on the
activation of trypsinogen to trypsin. Initially, this speculation was based on the role
trypsin plays in activating other digestive enzymes, all of which could contribute to
acinar cell damage in early pancreatitis. All of the major digestive enzymes, except
amylase and lipase, are synthesized as pro-enzymes or zymogens that require activation
through the cleavage of an activation peptide by trypsin. Normally, trypsinogen is
activated in the duodenum by the brush border enzyme, enterokinase, or by trypsin.
Trypsinogen can also autoactivate and that ability has become an important mechanism in
theories regarding the pathogenesis of acute pancreatitis. Because trypsinogen is stored
in the same compartment as other zymogens and it can autoactivate, there is always the
potential for premature trypsinogen activation within the acinar cell, which can set off a
cascade of zymogen activation leading to autodigestion of the pancreas.
With time, experimental evidence to support the role of premature trypsinogen
activation in acute pancreatitis has accumulated from studies in animal models and from
observations in humans. Production of trypsinogen activation peptide is one of the
earliest detectable events in models of experimental pancreatitis[7]. Pancreatitis
associated with endoscopic retrograde cholangiopancreatography (ERCP) can be
attenuated by pretreatment with trypsin inhibitors[8]. Perhaps, the most convincing
evidence for the importance of trypsin in the pathophysiology of acute pancreatitis comes
from genetic studies demonstrating an association of trypsin mutations with hereditary
pancreatitis[9●●].
A number of experimental studies in animal models support the important role of
trypsin in the pathophysiology of acute pancreatitis. Activation of trypsinogen, as
evidenced by the appearance of trypsin activation peptide, is first observed in
cytoplasmic vacuoles, whose formation is among the earliest detectable changes in the
acinar cell during experimental pancreatitis[4●, 10]. Both digestive enzymes and
lysosomal hydrolases co-localize in these vacuoles. Normally, digestive enzymes and
lysosomal hydrolases are packaged separately, but disruption of normal secretion as may
occur early in acute pancreatitis leads to a defect in intracellular transport and sorting of
enzymes. Once the digestive and lysosomal enzymes co-localize, lysosomal hydrolases
can activate trypsinogen. Cathepsin B may activate trypsinogen in the vacuoles as
evidenced by the observations that cathepsin B activates trypsinogen in vitro, that
specific cathepsin B inhibitors prevent the activation of trypsin in isolated acinar cells
after hyperstimulation with cerulein, a secretogogue, and that cathepsin B deficient mice
have decreased trypsinogen activation after the induction of pancreatitis[11]. Shortly
after forming, the vacuoles disintegrate and release their contents into the cytoplasm
where the activated digestive enzymes can now damage the acinar cell.
Important support for the central role of trypsinogen activation in acute
pancreatitis and a major advance in our understanding of the pathophysiology of
pancreatitis comes from genetic studies of families with recurrent pancreatitis in multiple
members[12●]. First described in 1952, hereditary pancreatitis causes repeated episodes
of acute pancreatitis and, in about 75% of patients, results in chronic pancreatitis. In
1996, a single point mutation in the third exon of the gene encoding cationic trypsinogen
was shown to segregate with the disease[13●]. The point mutation causes an arginine to
histidine substitution at position 122, R122H trypsinogen. Subsequently, additional
mutations in the trypsinogen gene were found in other pedigrees with hereditary
pancreatitis, including N29I, A16V, D22G, K23R and R122C. Three of these mutations,
R122H, R122C, and N29I, account for the majority of the patients[12●].
Increased resistance of the R122H mutant trypsin to the normal protective
mechanisms of the acinar cell has been proposed as a model for the defect in hereditary
pancreatitis[14]. Most protective mechanisms center on the control of trypsin levels in
the acinar cell by preventing trypsinogen activation, inhibiting or destroying active
trypsin, and flushing trypsin out of the pancreas. As mentioned above, the first lines of
defense against active trypsin accumulating in the cells are the synthesis trypsinogen and
the packaging of trypsinogen and other zymogens in granules, which isolates them from
other cellular enzymes like lysosomal hydrolases. If trypsinogen is activated inside the
cell, the product, trypsin, is inhibited by pancreatic secretory trypsin inhibitor (PSTI),
which is also known as serine protease inhibitor, Kazal type 1 (SPINK 1). Normally, the
pancreas synthesizes trypsinogen and SPINK1 at a molar ratio of 5 to 1. If trypsinogen
activation is brisk, the capacity of SPINK1 to inhibit trypsin becomes overwhelmed and
the next tiers of defense mechanisms come into play. Among these is the degradation of
trypsin by autolysis and, perhaps, by other proteases. The first step in degradation is
proteolytic cleavage after Arg122. In vitro studies demonstrate that R122H trypsin is
resistant to autolysis and also reveal that the mutation increases autoactivation of R122H
trypsinogen[15]. Similar studies on N29I cationic trypsinogen show that the mutation
results in faster autoactivation and increase trypsin stability[16]. Thus, both N29I and
R122H trypsin mutants are more likely to accumulate in acinar cells and cause increased
activation of other zymogens. Consequently, patients with these mutations develop
pancreatitis more readily than people who have normal trypsinogen.
Although autodigestion of the acinar cells by digestive enzymes plays a central
role in most theories of acute pancreatitis, other processes may also contribute to acinar
cell damage in early pancreatitis. Several authors have proposed an important role for
reactive oxygen species in acute pancreatitis[17, 18]. They point to studies showing
increases of lipid peroxides during experimental pancreatitis, alterations in cytoskeleton
function because of lipid peroxidation and increases in cell permeability that correlate
with the production of free oxygen radicals as evidence. Additionally, abnormalities of
the blood supply probably contribute to early injury. In experimental pancreatitis,
regions of the organ with good perfusion are less injured than regions with
hypoperfusion[19]. Finally, activation of resident macrophages in the pancreas and the
migration of activated leukocytes into the pancreas contribute to the severity of gland
inflammation in acute pancreatitis[20-22]. Nude mice lacking lymphocytes have
decreased severity of pancreatitis and the return of T-lymphocytes to these mice increases
the severity of acute pancreatitis.
Late Events in Acute Pancreatitis
The early events produce pancreatic edema and stimulate a local inflammatory response
associated with the release of inflammatory mediators into the systemic circulation[23,
24]. These cytokines and chemokines mediate a systemic inflammatory response, a
common pathway in many forms of injury. The clinical severity of pancreatitis depends
in part on the magnitude of the systemic response and the balance between pro-
inflammatory and anti-inflammatory mediators determines the clinical course. In
reaction to a brisk systemic inflammatory response, activated leukocytes migrate into
other organs, particularly the lungs, kidneys and liver, to cause tissue edema and damage.
According to current data, the activated immune response plays the major role in the
systemic complications of acute pancreatitis. Most likely, the damage of distant organs
by circulating pancreatic digestive enzymes is minimal.
Diagnosis of Acute Pancreatitis
The diagnosis of acute pancreatitis still depends on clinical suspicion and confirmatory
laboratory and radiographic studies[1-3●●]. Amylase and lipase remain the most
commonly employed laboratory tests. Other pancreatic products like phospholipase A2,
trypsin, trypsinogen activation peptide and elastase are elevated in acute pancreatitis, but
none have gained widespread use in the clinical laboratory. Although levels of lipase and
amylase that are three times the upper reference limit suggest pancreatitis, the level of
elevation is not diagnostic. Both enzymes can be elevated in conditions unrelated to
pancreatitis and both can be normal when there is radiographic evidence of acute
pancreatitis (Table 2).
Computed tomography (CT) and ultrasound images of the pancreas serve to
confirm the presence of pancreatitis, to identify complications and to investigate other
causes for the symptoms. Ultrasound findings included enlargement of the pancreas,
altered echogenicity of the pancreas, a dilated main pancreatic duct, gallstones, biliary
sludge, dilated common and intrahepatic ducts, pancreatic calcification, choledochal
cysts, and fluid collections. A CT scan will show similar findings, except that abnormal
attenuation is seen rather than altered echogenicity. Studies in animals indicate the CT
contrast given early in the course of acute pancreatitis may further diminish blood flow to
ischemic areas of the pancreas and increase the likelihood of necrosis. Although similar
studies have not been done in humans, it is reasonable to avoid CT scans early in the
course of pancreatitis and save this study for patients that do not show
improvement[1●●]. ERCP is reserved for patients with unexplained recurrent episodes
of pancreatitis, prolonged episodes of pancreatitis where a structural defect or duct
disruption is suspected, and in some cases of gallstone pancreatitis. Magnetic resonance
cholangiopancreatography (MRCP) can be helpful in defining abnormalities of the ductal
system and with the development of improved software MRCP may supplant ERCP as
the method of choice for evaluating the anatomy of the ductal system.
Treatment of Acute Pancreatitis
Treatment of pancreatitis has not changed significantly over the years. The mainstay of
treatment in children remains analgesia, intravenous fluids, pancreatic rest and
monitoring for complications[1●●]. Volume expansion early in the course of acute
pancreatitis is important to maintain cardiovascular stability and to prevent the
development of pancreatic necrosis. Nutrition should be implemented early if a severe or
prolonged course is anticipated. Until recently, parenteral nutrition was considered the
only option, but several studies show that adult patients with acute pancreatitis tolerate
jejunal feedings with fewer complications than those given parenteral nutrition[25].
Antibiotics are usually unnecessary except for the most severe cases.
Outcome of Acute Pancreatitis
Acute pancreatitis is usually divided into mild and severe forms. Because the clinical
course and outcome differ significantly between mild and severe cases, the physician
must make a rapid assessment of the patient’s condition and predict the risk of a mild or
severe clinical course. Several scoring systems have been developed to assist the
physician in this decision[26-28]. Until recently, none of these systems had been
validated in children. One group analyzed the criteria of the Ranson and Glasgow scores
plus additional criteria and developed a scoring system for children that was validated in
three centers[3●●]. Of note, young age and low weight are major risk factors.
Although acute pancreatitis can be life threatening, death does not occur in
pediatric patients as frequently as in adults[1●●]. Early causes of death are shock and
respiratory failure. Late life-threatening complications of pancreatitis are generally
associated with infected pancreatic necrosis and multi-system organ failure. Fortunately,
pancreatic necrosis appears to be uncommon in children and only 1 case in 380 (0.3%)
was found in patients from 7 centers[1●●, 3●●].
Prevalence of Chronic Pancreatitis
The prevalence of chronic pancreatitis in childhood is certainly less than that of acute
pancreatitis and the incidence may be increasing, but there are no reliable estimates of the
true prevalence.
Pathophysiology of Chronic Pancreatitis
Early in the course, chronic pancreatitis may be difficult to distinguish from acute
pancreatitis on clinical grounds[14]. In chronic pancreatitis continued inflammation
produces irreversible morphological changes in the gland such as fibrosis, acinar cell
loss, islet cell loss and infiltration by inflammatory cells. Because the diagnosis depends
on identifying decreased function and chronic changes, both of which occur late in the
course, studies of natural history and of potential therapies have been hindered.
Consequently, many theories to explain the pathophysiology of chronic pancreatitis have
been proposed.
In the last half of the twentieth century, the dominant view held that recurrent
acute pancreatitis progressed to chronic pancreatitis although some authors developed
theories that did not include acute pancreatitis as part of the pathway to chronic
pancreatitis. Current research suggests that chronic pancreatitis is a progression that
begins with acute pancreatitis and continues with chronic and recurrent inflammation to
produce end stage fibrosis[29]. In the last decade, it has become clear that susceptibility
to chronic pancreatitis is influenced by both genetic and environmental factors. In
children, chronic pancreatitis generally associates with abnormal genetic alleles or is
idiopathic.
Genetics of Chronic Pancreatitis
Trypsinogen mutations associate with the majority of hereditary pancreatitis kindreds.
As discussed above, the most common mutations include the cationic trypsinogen R122H
and N29I mutations. Hereditary pancreatitis caused by these mutations usually presents
as recurrent acute pancreatitis in childhood with a median age of 10 years with a range of
>1year to 60 years of age[9●]. In 50% of patients, chronic pancreatitis develops about 10
years after the first bout of acute pancreatitis although some patients will present with
chronic pancreatitis without a clear history of acute pancreatitis[30]. The most important
clinical clue is the presence of pancreatitis in other family members. The diagnosis is
confirmed by testing of the gene encoding cationic trypsinogen.
The association of cationic trypsinogen with hereditary pancreatitis led to the
search for families with mutations in SPINK1. By 2000, mutations in the gene encoding
SPINK1, N34S and P55S, were correlated with idiopathic chronic pancreatitis[31].
Almost 90% of patients with SPINK1 mutations develop pancreatitis before the age of
twenty. Interestingly, the mutations implicated in chronic pancreatitis are found in 1-4%
of the population, yet most of these carriers do not develop pancreatitis. In fact, the risk
of a SPINK1 mutation carrier developing chronic pancreatitis is about 1%. SPINK1
mutations probably increase susceptibility to recurrent acute and chronic pancreatitis
when homozygous mutations are present or in association with mutations in other genes
as part of a polygenic condition with multiple genetic risk factors.
In pediatrics, cystic fibrosis is the most common cause of chronic pancreatitis[32].
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause
cystic fibrosis. CFTR is a membrane protein located on the apical membrane of
pancreatic duct cells where it regulates water flow and chloride conductance. Over 1000
identified mutations organize into 5 major classes depending on the effect of the mutation
on CFTR protein expression and function. Some mutations completely abrogate CFTR
function and are classified as severe. Other mutations permit some function and are
classified as mild or variable. Patients with two severe alleles have classic cystic fibrosis.
Those who are compound heterozygotes for a severe and a mild allele have some residual
CFTR function and generally have atypical symptoms. In particular, compound
heterozygote mutations have been associated with chronic pancreatitis. Initial reports
found a correlation between mutations in a single CFTR allele and chronic pancreatitis,
but a later study with a more detailed analysis of the CFTR alleles correlated risk with
having two CFTR mutations[33-35]. These patients with one severe and one mild-
variable mutation have a 40-fold increase in the risk of developing chronic pancreatitis
over the general population.
Recently, it was suggested that CFTR mutation-associated pancreatitis can be
divided into 4 subtypes based on potential mechanisms[36]. Type 1 is classic CF with
two severe alleles. Type 2 is atypical CF with a severe and mild-variable genotype. Of
specific interest are CFTR mutations that block bicarbonate conductance but not chloride
conductance. These mutations can potentially target the pancreas over other organs since
bicarbonate secretion by duct cells is central to pancreatic fluid secretion and function.
Type 3 is a severe or a mild-variable CFTR allele plus a second susceptibility gene. For
instance, the risk for developing chronic pancreatitis was increased 900-fold in patients
with heterozygous mutations in both the CFTR and SPINK1 genes[33]. Type 4 is a
heterozygote with a severe or mild-variable allele and a strong environmental risk factor
like alcohol.
Genetic Testing in Recurrent or Chronic Pancreatitis
Genetic testing for pancreatic diseases has become an important part of medical
practice[37●-39]. The purpose of genetic testing can be divided into two general
categories, diagnostic and predictive. Diagnostic testing is done when a patient has
symptoms of a disease and a genetic test can determine the underlying cause. Predictive
testing is genetic testing in subjects who do not have evidence of pancreatic disease, but
may have relatives with pancreatic disease or a known mutation in the genes encoding
CFTR or cationic trypsinogen. In general the indications for diagnostic testing validate
its use, but the role of predictive testing is less clear and controversial.
The primary indications for R122H and N29I cationic trypsinogen mutation
testing are diagnostic and include recurrent idiopathic acute pancreatitis, idiopathic
chronic pancreatitis, and patients with a family history of acute pancreatitis (Table 3).
Early identification of a cationic trypsinogen gene mutation can prevent an expensive and
prolonged evaluation of recurrent pancreatitis in children. Knowledge of the diagnosis
also allows the physician to counsel the family and patient about the natural history of the
disease, particularly the greatly increased risk for pancreatic cancer[40].
Some have advocated predictive genetic testing in family members with first
degree relatives that have a mutation in the gene encoding cationic trypsinogen. A
negative test result in a family with a known mutation essentially eliminates the risk of
this genetic form of pancreatitis. A positive test result in a clinically unaffected person
confers a significantly increased risk of pancreatitis, which may diminish with age.
Those who argue for testing point out that alcohol, tobacco, emotional stress and fatty
foods may precipitate attacks of pancreatitis in patients with hereditary pancreatitis.
Others respond that counseling to avoid fatty foods, alcohol, and tobacco represents
excellent general medical advice and therefore does not provide a compelling reason for
genetic testing[39]. In either case, the patient and their family should be offered adequate
genetic counseling and the personal desires of older children should be considered. Both
physicians and patients need to understand the implications of genetic testing for the
patient’s future health, family, employment and insurability. Older children may
postpone testing or may proceed with testing to relieve their own anxieties and to learn
more about their personal health.
Although testing for SPINK1 mutations in children with chronic pancreatitis may
provide information about predisposing factors, most experts do not advocate genetic
testing for SPINK1 mutations at this time[41, 42]. Heterozygous SPINK1 mutations
alone are probably not disease causing[43]. Homozygous mutations are strongly
associated with chronic pancreatitis, but may still be part of a polygenic disorder. Thus,
identifying a SPINK1 mutation does not preclude the search for other causes of chronic
pancreatitis. Genetic testing in pre-symptomatic individuals is futile since less than 1%
of patients who are heterozygotes for a SPINK1 mutation will develop pancreatitis.
There has been much interest in testing patients with idiopathic chronic
pancreatitis for CFTR mutations. The major problem with this approach is that currently
available panels only test for the most common CF-causing gene mutations, not
pancreatitis associated mutations. Less common or unique mutant alleles will not be
identified unless broader screening procedures become available. New techniques, such
as denaturing ion-pair reverse-phase high-performance liquid chromatography, show
promise for rapidly analyzing the complete coding sequence of the CFTR gene. These
new tools will allow investigators to fully interpret the CFTR genotype-pancreatitis
relationship which will provide the basis for recommendations on the utility of genetic
screening for CFTR mutations in patients with chronic pancreatitis. On the other hand,
acute pancreatitis may be the first sign of CF or atypical CF and these children should
undergo an evaluation for CF. The evaluation should begin with a sweat test and genetic
testing should be considered only when family history or other symptoms suggest
atypical CF.
Conclusions
Inflammatory disorders of the pancreas are seen with regularity in regional children’s
hospitals. Both acute and chronic pancreatitis occur in childhood and the incidence may
be increasing. Important differences in the etiologies between children and adults exist
for both acute and chronic pancreatitis, but the treatment is the same. The greatest
progress in understanding the pathophysiology of pancreatitis has come from studies
linking genetic mutations to increased risk for pancreatitis. Mutations in the gene
encoding cationic trypsinogen cause hereditary pancreatitis. Mutations in genes encoding
CFTR and SPINK1 act as modifiers that along with other factors, such as other genes,
drugs or toxins, increase the risk of developing pancreatitis. A greater understanding of
the genes involved in pancreatitis and in the biological events associated with pancreatitis
will eventually lead to better diagnostic methods, new treatments and improved
prevention of pancreatic inflammatory disease.
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The paper provides a good synopsis of the many issues related to genetic testing.
38. Applebaum-Shapiro SE, Peters JA, O'Connell JA, et al.: Motivations and
concerns of patients with access to genetic testing for hereditary pancreatitis. Am
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39. Applebaum SE, Kant JA, Whitcomb DC, et al.: Genetic testing. Counseling,
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40. Lowenfels AB, Maisonneuve P, Whitcomb DC, et al.: Cigarette smoking as a risk
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41. Whitcomb DC: Motion--genetic testing is useful in the diagnosis of nonhereditary
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42. Cohn JA: Motion--genetic testing is useful in the diagnosis of nonhereditary
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Gastroenterology 2000, 119:615-623.
Werlin et al. [1] Lopez [2] Debanto et al. [3]
Number of cases 180 274 301
Systemic 18 48 10
Gallstone 12 4
Structural 8 10 2
Infectious 8 3 3
Medications 12 5 11
Trauma 14 19 13
Post ERCP 6 3
Familial 3 5
Cystic Fibrosis 0.6 2
Idiopathic 8 17 34
Other 21 8 13
Table 1. Etiologies of acute pancreatitis in three recent studies of children
Table 2. Causes of elevated amylase or lipase
Pancreatic Disease Nonpancreatic Causes
Acute pancreatitisChronic pancreatitisPancreatic ascitesPancreatic cancerPseudocyst
SalpingitisSalivary adenitisEnd-stage renal diseaseBurnsAcute cholecystitisUpper endoscopyMacroamylasemiaMacrolipasemia
Table 3. Indications for genetic testing for cationic trypsinogen mutations
a. Recurrent attacks of acute pancreatitis with no apparent etiology.
b. Idiopathic chronic pancreatitis.
c. History of pancreatitis is a first, second or third degree relative.
d. An unexplained episode of documented pancreatitis occurring in a child that has required hospitalization.
e. As part of an Institutional Review Board approved research protocol.