Pancreatic Disorders

Once considered uncommon, pancreatic diseases are increasingly recognized in the pediatric age group. Acute pancreatitis, acute recurrent pancreatitis, and chronic pancreatitis occur in children with an incidence approaching that of adults. Risk factors are broad, prompting the need for a completely different diagnostic and therapeutic approach in children. Although cystic fibrosis remains the most common cause of exocrine pancreatic insufficiency, other causes such as chronic pancreatitis may be as common as Shwachman Diamond syndrome. Long-term effects of pancreatic diseases may be staggering, as children suffer from significant disease burden, high economic cost, nutritional deficiencies, pancreatogenic diabetes, and potentially pancreatic cancer.

Key points

  • •

    Once considered rare, pancreatic diseases, specifically acute, acute recurrent, and chronic pancreatitis, are increasingly recognized in children.

  • •

    Etiologies and risk factors of adult and pediatric pancreatitis are very different; therefore it is expected that their management, natural history, and response to therapy would also be different; however, studies on pediatric pancreatitis are limited.

  • •

    Genetic risk factors seem to play a role in the progression from acute recurrent to chronic pancreatitis; disease burden is high in chronic pancreatitis.

  • •

    Cystic fibrosis is the most common cause of exocrine pancreatic insufficiency in children; chronic pancreatitis and Shwachman Diamond syndrome are second most common.

  • •

    There is an urgent need for an exocrine pancreatic function that would be simple to perform, accurate, reliable, reproducible, and noninvasive.

Pediatric pancreatic diseases are increasingly recognized in childhood, possibly because of increased awareness among physicians. Acute pancreatitis (AP) is estimated to occur at an incidence approaching that of adults. Although AP resolves without complications in most children, a subset continues to have recurrent attacks of pancreatitis (acute recurrent pancreatitis or ARP), and some progress to chronic pancreatitis (CP). In contrast to the adult population, most children with ARP or CP have genetic mutations; environmental risk factors are rare. Disease burden is significant in CP. Cystic fibrosis (CF) is the most common cause of exocrine pancreatic insufficiency (EPI) in childhood, followed by Shwachman-Diamond syndrome (SDS) and CP. Long-term effects of pancreatic diseases in children include possible nutritional deficiencies, pancreatogenic diabetes, and potentially pancreatic cancer later in life.

Acute pancreatitis

Risk Factors/Etiologies

Recent studies estimate the incidence of AP at between 3.6 and 13.2 cases per 100,000 children per year, which is similar to incidences reported in adults. Box 1 lists etiologies of AP in children.

Box 1

  • Biliary/obstructive factors (10%–30%)

  • Gallstones/biliary sludge

  • Choledocholithiasis

  • Choledochal cyst

  • Ampullary obstruction

  • Pancreas divisum

  • Anomalous biliopancreatic junction (union)

  • Annular pancreas

  • Systemic diseases/inflammation/infection (10%–50%)

  • Shock/hypoperfusion state

  • Inflammatory bowel disease

  • Hemolytic–uremic syndrome

  • Henoch-Schonlein purpura

  • Inflammatory bowel disease

  • Kawasaki disease

  • Malnutrition/anorexia nervosa

  • Primary sclerosing cholangitis

  • Sickle cell disease

  • Autoimmune pancreatitis

  • Sepsis/bacteremia

  • Bacterial infections

    • Campylobacter jejuni

    • Mycoplasma

    • Staphylococcus aureus

  • Viral infections

    • Adenovirus

    • Coxsackie

    • Cytomegalovirus

    • Epstein-Barr virus

    • Echovirus

    • Human immunodeficiency syndrome

    • Mumps

    • Herpes simplex virus

  • Medications (5%–25%)

  • Valproic acid

  • 6-mercaptopurine/azathioprine

  • l -asparaginase

  • Mesalamine

  • Trimethoprim/sulfamethoxazole

  • Furosemide

  • Tacrolimus

  • Steroids

  • Trauma (10%–20%)

  • Blunt abdominal trauma/child abuse

  • Duodenal hematoma

  • Post-ERCP pancreatitis

  • Metabolic diseases (5%–10%)

  • Diabetes mellitus/diabetic ketoacidosis

  • Hypertriglyceridemia

  • Glycogen storage disease

  • Organic acidemia (eg, methylmalonic acidemia)

  • Hypercalcemia

  • Idiopathic (15%–30%)

  • Genetic mutations (rare)

    • PRSS1

    • CFTR

    • SPINK1

    • CTRC

    • CPA1

    • CEL

    • CEL-HYB

  • Malignancy (rare)

    • Lymphoma

    • Neuroblastoma

Abbreviations: CEL, carboxylesterlipase; CEL-HYB, CEL-Hybrid; CFTR, cystic fibrosis transmembrane generator; CPA1, carboxypeptidase 1; CTRC, chymotrypsin-C; PRSS1, cationic trypsinogen; SPINK1, serine protease inhibitor Kazal type I.

Etiologies of pediatric acute pancreatitis
Data from Refs.

There are unique differences between risk factors of adult and pediatric AP. In adults, alcohol use and gallstones account for the majority of cases, while etiologies in children are broad and variable. Biliary/obstructive factors, systemic illness, and medications are commonly identified in childhood AP; 15% to 30% cases are idiopathic. AP triggered by genetic mutations, metabolic factors, trauma, or alcohol is uncommon in children. In infants and toddlers, systemic illness is the leading cause.

Pathophysiology

Pancreatitis may occur in the setting of an inciting factor (eg, medication, obstruction, genetic mutation) that triggers a cascade of events. There are several competing mechanisms of pancreatic inflammation including

  • The traditional trypsin-dependent theory (activation of the enzymes leading to destruction of pancreas)

  • Inflammatory pathways (supported by animal models lacking trypsinogen and still developing inflammation)

  • Endoplasmic reticulum stress (independent of trypsin activation)

Models that mimic human disease are needed to better dissect the mechanisms of pancreatic inflammation.

Clinical Manifestations

The most common symptoms of AP are abdominal pain and vomiting. Young children may present with vague symptoms and/or irritability; thus diagnosis in this age group requires a high degree of suspicion. Signs and symptoms of cholangitis may be present in gallstone pancreatitis, but mild jaundice and liver enzyme elevations may occur in nonbiliary pancreatitis due to significant inflammatory changes in the distal bile duct as it traverses through the head of the pancreas.

Diagnosis

AP is a clinical diagnosis based on a combination of history, physical examination, laboratory testing, and imaging findings as listed in Table 1 .

Table 1
Definitions of pancreatitis in children (INSPPIRE criteria)
Clinical Definition
AP

  • Requires at least 2 out of 3 criteria:

    • 1.

      Abdominal pain suggestive of, or compatible with AP

    • 2.

      Serum amylase and/or lipase activity at least 3 times greater than the upper limit of normal

    • 3.

      Imaging findings characteristic of, or compatible with AP

ARP

  • Requires at least 2 distinct episodes of AP, plus:

    • •

      Complete resolution of pain (≥1 mo pain-free interval between the diagnoses of AP).

  • Or

    • •

      Complete normalization of amylase and lipase in between episodes.

CP

  • Requires at least 1 of the following 3:

    • 1.

      Abdominal pain consistent with pancreatic origin and imaging findings suggestive of chronic pancreatic damage a

    • 2.

      Evidence of exocrine pancreatic insufficiency and suggestive pancreatic imaging findings a

    • 3.

      Evidence of endocrine pancreatic insufficiency and suggestive pancreatic imaging findings a

Ductal changes: irregular contour of the main pancreatic duct or its radicles; intraductal filling defects; calculi, stricture or dilation; Parenchymal changes: generalized or focal enlargement, irregular contour (accentuated lobular architecture), cavities, calcifications, heterogeneous echotexture.
From Morinville VD, Husain SZ, Bai H, et al. Definitions of pediatric pancreatitis and survey of present clinical practices. J Pediatr Gastroenterol Nutr 2012;55:261–5.

a “Suggestive” imaging findings of CP include.

Laboratory findings

Amylase and lipase are the most commonly used biochemical markers of pancreatic inflammation. Amylase and lipase elevations are not specific for AP, but lipase appears to be a more sensitive marker for pancreatitis. In the absence of a known etiology or family history, liver indices (aminotransferases, conjugated and unconjugated bilirubin and GGT), along with fasting glucose, triglycerides, and calcium are recommended laboratory studies for the first episode of AP.

Imaging findings

Imaging may be done to confirm AP and/or its complications, assessing pancreatic parenchyma and the surrounding organs and vasculature. Imaging may include transabdominal ultrasound (TUS), contrast-enhanced computed tomography (CECT), MRI of the abdomen including magnetic resonance cholangiopancreatography (MRCP), and endoscopic ultrasound (EUS).

In children, TUS is the first-line study based on its diagnostic yield and safety profile. In AP, the pancreas may appear normal on TUS, or difficult to visualize because of intestinal air; echogenicity may be variable. The advantages of TUS are its lower cost compared with other modalities, no need for sedation, and no ionizing radiation. TUS is useful for identifying biliary tract disease, including gallstones, choledochal cyst, common bile duct stones, or biliary tract dilation. TUS can also identify acute fluid collections, peripancreatic inflammation, and masses. The use of Doppler may delineate splenic vein thrombosis or other vascular changes.

Cross-sectional imaging such as CECT and MRI have a limited role in AP. CECT can provide high-resolution images and assess pancreatic parenchyma, peripancreatic tissues, and nearby vessels and organs, but it is not effective in assessing nondilated pancreatic ducts. CECT is routine in adult patients with pancreatitis, but because of risks of ionizing radiation, it is not routinely performed in pediatrics. Of note, recent adult guidelines recommend deferring CECT and/or MRI for the first 48 to 72 hours unless the diagnosis is in question or in those who fail to demonstrate clinical improvement.

MRI/MRCP is not typically ordered for AP. The 2 most common scenarios in which MRI, specifically MRCP, is useful in children are (1) young children with pancreatitis to identify significant pancreatic anomalies and (2) patients with gallstone pancreatitis with inconsistent laboratory and ultrasound findings. The most significant risk–benefit assessment for pediatric patients in using MRI is the possible need for sedation/anesthesia for completion of the study. MRCP does not require contrast, but gadolinium and related magnetic resonance contrast agents should be used with caution in those with renal impairment or allergy to the agents.

Complications

In general, AP has a mild course in childhood and resolves without significant complications. When complications occur, they can be local or systemic. Local complications include acute peripancreatic fluid collection, pancreatic pseudocyst ( Fig. 1 ), acute necrotic collection, and walled-off necrosis ( Table 2 ). They should be suspected when there is persistence or recurrence of abdominal pain, secondary increases in pancreatic enzymes, organ dysfunction, or signs and symptoms of sepsis, such as fever and leukocytosis. Other local complications are poor gastric motility, splenic and portal vein thrombosis, and colonic necrosis. Systemic complications include organ failure, most commonly respiratory, cardiovascular, and renal. The 2012 Atlanta classification grades AP severity as mild, moderately severe, or severe ( Box 2 , Fig. 2 ).

Fig. 1
CT scan showing pancreatic pseudocyst following a PEG-asparaginase induced AP in a child.
Table 2
Morphologic classification of acute pancreatitis
Morphologic Type Definition Contrast Enhanced CT Findings
IEP Acute inflammation of the pancreatic parencyhma and peripancreatic tissues without recognizable tissue necrosis
  • •

    Pancreatic parenchyma enhanced by intravenous contrast

  • •

    No peripancreatic necrosis

Necrotizing Pancreatitis Inflammation associated with pancreatic parenchymal necrosis and/or peripancreatic necrosis
  • •

    Pancreatic parenchyma not enhanced by intravenous contrast and/or

  • •

    Presence of peripancreatic necrosis (ANC and WON)

Acute Peripancreatic Fluid Collection (APFC)
  • •

    Peripancreatic fluid associated with interstitial edematous pancreatitis with no associated peripancreatic necrosis.

  • •

    Only applies to fluid seen within the first 4 wk and without features of a pseudocyst

  • •

    Occurs in the setting of IEP

  • •

    Homogenous collection with fluid density, no nonliquid component

  • •

    Confined by normal peripancreatic fascial planes

  • •

    No definable wall encapsulating the collection

  • •

    Adjacent to pancreas (without intrapancreatic extension)

Pancreatic pseudocyst ( Fig. 1 )
  • •

    An encapsulated collection of fluid with a well-defined inflammatory wall

  • •

    Usually outside the pancreas with minimal or no necrosis.

  • •

    Occurs after IEP

  • •

    Homogenous fluid density

  • •

    No nonliquid component

  • •

    Well defined wall (completely encapsulated)

  • •

    Usually >4 wk after onset of AP

Acute Necrotic Collection
  • •

    Collection containing variable amounts of both fluid and necrotic material

  • •

    Associated with necrotizing pancreatitis

  • •

    Involves pancreatic parenchyma or peripancreatic tissues

  • •

    Rare in children

  • •

    Occurs only with acute necrotizing pancreatitis

  • •

    Heterogeneous and nonliquid density of varying degrees in different locations

  • •

    No definable wall encapsulating the collection

  • •

    Intrapancreatic and/or extrapancreatic

Walled-Off Necrosis (WON)
  • •

    Mature encapsulated collection of pancreatic and/or peripancreatic necrosis

  • •

    Usually occurs >4 wk after onset of necrotizing pancreatitis

  • •

    Rare in children

  • •

    Heterogeneous with liquid and nonliquid density, varying degrees of loculations

  • •

    Well-defined wall, completely encapsulated

  • •

    Intrapancreatic and/or extrapancreatic

Adapted from Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62:102–11.
Box 2

  • Mild AP

  • No organ failure

  • No local or systemic complications

  • Moderately severe AP

  • Organ failure that resolves within 48 hours (transient)

  • Local or systemic complications without persistent organ failure

  • Severe AP

  • Persistent organ failure more than 48 hours (either single or multiple organ failure)

Grades of pancreatitis severity
Adapted from Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62:102–11.
Fig. 2
CT scan in moderately severe pancreatitis in a teenager with gallstone pancreatitis. Pancreatic and peripancreatic inflammatory changes are seen.

The scoring systems to assess the severity of pancreatitis in adults (Ranson, Glasgow, modified Glasgow, Bedside Index of Severity in Acute Pancreatitis [BISAP], and Acute Physiology and Chronic Health Evaluation [APACHE], II) cannot be easily applicable to children. The DeBanto scoring system was the first system to assess severity in a pediatric cohort. A more recent scoring system proposes using lipase, albumin, and white blood cell count (WBC) obtained within 24 hours of admission to predict severity. Developing a severity score in pediatrics is challenging, as severe complications are uncommon, and death is very rare.

Management

The most important component in the management of AP is fluid therapy ( Fig. 3 ). Fluid resuscitation is thought to maintain pancreatic microcirculation and prevent major complications, such as necrosis and organ failure. Lactated ringer has been shown to reduce systemic inflammation and thus prevent complications in adults with AP compared to saline. Early and aggressive fluid resuscitation in children with normal saline and 5% dextrose is safe and well-tolerated, but has not been compared with other fluids. The rates of intravenous fluid in pediatric AP have also not been assessed. One study showed that a combination of early enteral nutrition (<48 hours) and aggressive fluid management (>1.5–2× maintenance within the first 24 hours) decreased length of stay and complications.

Fig. 3
Algorithm for management of AP and complications.

In both children and adults, the initial nutritional management of AP remains controversial. The American College of Gastroenterology recommends oral feedings for mild AP when patients’ symptoms are significantly improved, and feeding with a low-fat solid diet appears as safe as a clear liquid diet. Overall, it is agreed that children with mild-to-moderate disease require minimal to no additional nutritional support; enteral nutrition is preferred over parenteral nutrition, and nutritional support should begin within 48 to 72 hours. For patients with severe AP, enteral nutrition is recommended to prevent infectious complications, decrease inflammatory response, reduce mortality, and improve outcome. Early enteral nutrition appears to be safe in children, but more studies are needed.

Pain is managed with opioids, specifically intravenous morphine initially. Despite earlier concerns about Sphincter of Oddi dysregulation with morphine, there is no clinical evidence to support this theory. Once tolerating oral feedings, patients may transition to oral acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) alone or combined with an opioid.

Endoscopic procedures for AP are limited to EUS and ERCP. ERCP is recommended in gallstone pancreatitis with choledocholithiasis, cholangitis, or in those with concern for biliary obstruction. In adults with gallstone pancreatitis, EUS and MRCP are preferred in those without jaundice or cholangitis; however, this has not been formally studied in children. EUS drainage via endoscopic cystgastrostomy has become the standard modality for drainage of pancreatic pseudocysts and pancreatic necrosis in adults and children. Surgery for AP is infrequently performed, and typically for pseudocyst drainage, debridement of necrosis or cholecystectomy. Recent studies show that early cholecystectomy after mild biliary pancreatitis is safe in children and reduces readmissions.

Acute pancreatitis

Risk Factors/Etiologies

Recent studies estimate the incidence of AP at between 3.6 and 13.2 cases per 100,000 children per year, which is similar to incidences reported in adults. Box 1 lists etiologies of AP in children.

Box 1

  • Biliary/obstructive factors (10%–30%)

  • Gallstones/biliary sludge

  • Choledocholithiasis

  • Choledochal cyst

  • Ampullary obstruction

  • Pancreas divisum

  • Anomalous biliopancreatic junction (union)

  • Annular pancreas

  • Systemic diseases/inflammation/infection (10%–50%)

  • Shock/hypoperfusion state

  • Inflammatory bowel disease

  • Hemolytic–uremic syndrome

  • Henoch-Schonlein purpura

  • Inflammatory bowel disease

  • Kawasaki disease

  • Malnutrition/anorexia nervosa

  • Primary sclerosing cholangitis

  • Sickle cell disease

  • Autoimmune pancreatitis

  • Sepsis/bacteremia

  • Bacterial infections

    • Campylobacter jejuni

    • Mycoplasma

    • Staphylococcus aureus

  • Viral infections

    • Adenovirus

    • Coxsackie

    • Cytomegalovirus

    • Epstein-Barr virus

    • Echovirus

    • Human immunodeficiency syndrome

    • Mumps

    • Herpes simplex virus

  • Medications (5%–25%)

  • Valproic acid

  • 6-mercaptopurine/azathioprine

  • l -asparaginase

  • Mesalamine

  • Trimethoprim/sulfamethoxazole

  • Furosemide

  • Tacrolimus

  • Steroids

  • Trauma (10%–20%)

  • Blunt abdominal trauma/child abuse

  • Duodenal hematoma

  • Post-ERCP pancreatitis

  • Metabolic diseases (5%–10%)

  • Diabetes mellitus/diabetic ketoacidosis

  • Hypertriglyceridemia

  • Glycogen storage disease

  • Organic acidemia (eg, methylmalonic acidemia)

  • Hypercalcemia

  • Idiopathic (15%–30%)

  • Genetic mutations (rare)

    • PRSS1

    • CFTR

    • SPINK1

    • CTRC

    • CPA1

    • CEL

    • CEL-HYB

  • Malignancy (rare)

    • Lymphoma

    • Neuroblastoma

Abbreviations: CEL, carboxylesterlipase; CEL-HYB, CEL-Hybrid; CFTR, cystic fibrosis transmembrane generator; CPA1, carboxypeptidase 1; CTRC, chymotrypsin-C; PRSS1, cationic trypsinogen; SPINK1, serine protease inhibitor Kazal type I.

Etiologies of pediatric acute pancreatitis
Data from Refs.

There are unique differences between risk factors of adult and pediatric AP. In adults, alcohol use and gallstones account for the majority of cases, while etiologies in children are broad and variable. Biliary/obstructive factors, systemic illness, and medications are commonly identified in childhood AP; 15% to 30% cases are idiopathic. AP triggered by genetic mutations, metabolic factors, trauma, or alcohol is uncommon in children. In infants and toddlers, systemic illness is the leading cause.

Pathophysiology

Pancreatitis may occur in the setting of an inciting factor (eg, medication, obstruction, genetic mutation) that triggers a cascade of events. There are several competing mechanisms of pancreatic inflammation including

  • The traditional trypsin-dependent theory (activation of the enzymes leading to destruction of pancreas)

  • Inflammatory pathways (supported by animal models lacking trypsinogen and still developing inflammation)

  • Endoplasmic reticulum stress (independent of trypsin activation)

Models that mimic human disease are needed to better dissect the mechanisms of pancreatic inflammation.

Clinical Manifestations

The most common symptoms of AP are abdominal pain and vomiting. Young children may present with vague symptoms and/or irritability; thus diagnosis in this age group requires a high degree of suspicion. Signs and symptoms of cholangitis may be present in gallstone pancreatitis, but mild jaundice and liver enzyme elevations may occur in nonbiliary pancreatitis due to significant inflammatory changes in the distal bile duct as it traverses through the head of the pancreas.

Diagnosis

AP is a clinical diagnosis based on a combination of history, physical examination, laboratory testing, and imaging findings as listed in Table 1 .

Table 1
Definitions of pancreatitis in children (INSPPIRE criteria)
Clinical Definition
AP

  • Requires at least 2 out of 3 criteria:

    • 1.

      Abdominal pain suggestive of, or compatible with AP

    • 2.

      Serum amylase and/or lipase activity at least 3 times greater than the upper limit of normal

    • 3.

      Imaging findings characteristic of, or compatible with AP

ARP

  • Requires at least 2 distinct episodes of AP, plus:

    • •

      Complete resolution of pain (≥1 mo pain-free interval between the diagnoses of AP).

  • Or

    • •

      Complete normalization of amylase and lipase in between episodes.

CP

  • Requires at least 1 of the following 3:

    • 1.

      Abdominal pain consistent with pancreatic origin and imaging findings suggestive of chronic pancreatic damage a

    • 2.

      Evidence of exocrine pancreatic insufficiency and suggestive pancreatic imaging findings a

    • 3.

      Evidence of endocrine pancreatic insufficiency and suggestive pancreatic imaging findings a

Only gold members can continue reading. Log In or Register to continue

Related posts:

  1. Pediatric Gastroenterology
  2. Motility Disorders in Children
  3. Pediatric Inflammatory Bowel Disease
  4. The Transition of the Gastrointestinal Patient from Pediatric to Adult Care

Stay updated, free articles. Join our Telegram channel
Tags:
Oct 2, 2017 | Posted by in PEDIATRICS | Comments Off on Pancreatic Disorders

Full access? Get Clinical Tree
Get Clinical Tree app for offline access