Peptic Ulcer Disease in Children

Adam G. Mezoff, MD,* and William F. Balistreri, MDt

Secondary ulcers are associated with sive. Alcohol can damage gastric mu-
FOCUS QUESTIONS a known ulcerogenic event such as cosa and, thus, lead to gastritis, but it
1. Which are the principal risk fac-
stress, burns, or ingestion of nonste- does not appear to cause duodenal
tors for peptic ulcer disease roidal anti-inflammatory medications. ulcer.
among infants, children, and A discussion of peptic inflammation Although aspirin (ASA) and non-
adolescents? that typically does not cause ulcer- steroidal anti-inflammatory drugs
2. What is the pathophysiology of
ation, such as esophagitis, is beyond (NSAIDs) can cause gastric mucosal
peptic ulcer disease?
3. How should the pediatrician eval- the scope of this review. damage and produce gastric ulcers,
uate a child in whom peptic ulcer an association with duodenal ulcers is
is suspected? not conclusive. Corticosteroids also
4. What are the mechanisms of ac- Epidemiology have been implicated in the patho-
tion and indications for use of H2
blockers, sucralfate, and prosta- genesis of peptic ulcer disease, but
PRIMARY PEPTIC ULCERS
glandins in the treatment of peptic this also is controversial. Recent
ulcer? Duodenal Ulcers
studies suggest a significant incidence
Approximately 4 to 8 million adults of peptic inflammation in association
in the United States suffer from duo- with combined use of corticosteroids
denal ulcers; about 200 000 to and NSAIDs. Tolazoline, used for
The term peptic ulcer disease de-
400 000 new cases are discovered pulmonary hypertension in neonates,
scribes a group of disorders, rather
each year. The incidence (new cases causes histamine release and in-
than a single pathologic process. It is
per population base in a given period creased gastric acid secretion, which
recognized increasingly in children,
of time) is 0.15% in males and can lead to ulcers.
often with long-term ramifications. In
0.03% in females. The prevalence There is strong evidence that
the past decade, management of pa-
(proportion of the population that has smoking cigarettes not only leads to
tients who have peptic ulcer disease
a given disease over time) is I .9% duodenal ulcers but slows healing
has changed dramatically. Antacid
for males and 2.0% for females. and increases recurrence rates, as
therapy has given way to treatment
Males tend to develop duodenal ul- well. Smokers are twice as likely as
with histamine (H2) receptor antago-
cers earlier than females (25 years nonsmokers to develop both duodenal
nists, a new class of pharmacologic
versus 45 years of age). and gastric ulcer disease.
agents that has fostered a billion dol-
The number of children who have Stress is another factor commonly
lar industry. Other modalities of
duodenal ulcers, as reported from implicated in the pathogenesis of du-
treatment have been developed as
large pediatric centers, is about 5.4 odenal ulcer. The emotional state of a
well, such as cytoprotective agents
new cases per hospital per year. The patient may alter basal acid secretion
(sucralfate) and proton pump inhibi-
incidence in males is two to three and the sensitivity of parietal cells to
tors (omeprazole), which are based
times higher than in females, with the exogenous stimulation, but there are
on research into the pathophysiology
exception of very young patients, for no conclusive studies linking stress to
of gastric acid disorders. In addition,
whom the incidence is similar in both the genesis of duodenal ulceration.
the discovery of an infectious agent
sexes. Fifty percent of pediatric pa- Substantial evidence links familial
(Helicobacter pylon) that contributes
tients who have duodenal ulcers have predisposition (Table 1) and genetic
to the formation of peptic ulcers has
a family member who has peptic ul- background (Table 2) to the forma-
led to a reevaluation of the traditional
cer disease compared with 20% of tion of duodenal ulcers. Familial ag-
approach to diagnosis and treatment
patients who have the onset of peptic gregates account for 20% to 50% of
of abdominal pain in children.
ulcer disease after the third decade patients who have duodenal ulcer
Duodenal ulcers are defined as mu-
of life. disease. The first-degree relatives of
cosal defects penetrating the mucosa,
Several predisposing factors have patients who have duodenal ulcers
submucosa, and muscularis mucosa
been implicated in the development have a threefold increase in preva-
of the duodenum. Gastric ulcers are
of peptic ulcer disease in patients of lence of duodenal ulcers. Up to two
defined as mucosal defects that pene-
all ages. Dietary factors have been thirds of children who have ulcers
trate the muscularis mucosa of the
thought to play a major role in the have a first-degree relative who has
stomach. Primary ulcers are those
development of this disorder, but peptic ulcer disease. Studies of twins
that have no known underlying cause.
there is no convincing evidence that show a 50% concordance for
diet affects its incidence. Although monozygotic twins in the develop-
*Assistant Professor of Pediatrics and caffeine-containing beverages (coffee, ment of peptic ulcer disease com-
Medicine, Wright State University School of tea, soft drinks), which are strong pared with 14% in dizygotic twins.
Medicine, Director, Gastroenterology &
stimulants of acid secretion, have Predisposition to duodenal ulcer
Nutrition, Childrens Medical Center,
Dayton, OH. been suggested as etiologic agents in formation also is associated with
tprofessor of Pediatrics and Director, the formation of duodenal ulcers, seemingly unrelated genetic factors.
Gastroenterology & Nutrition, Children s evidence establishing their role in Individuals who have blood group
Hospital Medical Center, Cincinnati OH. peptic ulcer formation is inconclu- type 0 have a 30% increased risk for

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 #{149}
GASTROENTEROLOGY
Peptic Ulcers

known. In Japan they occur five to

TABLE 1. Subtypes of ten times more often than duodenal TABLE 2. Rare Genetic
Familial Duodenal Ulcer ulcers. In the United States, there are Syndromes Associated With
Disease four times as many duodenal as gas- Duodenal Ulcers
tric ulcers. Gastric ulcers occur with
#{149}
Hyperpepsinogenemia I #{149}
Multiple endocrine
the same frequency in men and
women. They rarely develop before adenomatosis, type I (from
#{149}
Antral 0 cell hyperfunction
gastrmn-producing islet cell
age 40, and the incidence peaks be-
#{149}
Normopepsinogenemia I tumors)
tween 55 and 65 years of age. The
presence of multiple gastric ulcers #{149}
Systemic mastocytosis
#{149}
Rapid gastric emptying
does not increase the likelihood of (30%-40% have ulcers)
#{149}
Childhood or early onset recurrence. The incidence of coexist-
duodenal ulcer ent duodenal ulcers in patients who #{149}
Ulcer-tremor-nystagmus
-With postprandial have gastric ulcers ranges from 7%
#{149}
Amyloidosis, type IV
hypergastrimemia to 64%.
-With elevated acid secretion Dietary factors such as caffeine or #{149}
Stiff-skin syndrome
alcohol ingestion have not been
#{149}
Combined duodenal and gastric #{149}
Pachydermoperiostosis
proven to cause gastric ulcers, al-
ulcer?
though alcohol can lead to gastritis. #{149}
Multiple lentigines-ulcer
#{149}
Immunologic forms of Medications such as salicylates and syndrome
duodenal ulcer?? other NSAIDs have been shown to
cause gastric ulcers. The role of ste- #{149}
Leukonychia-gallstone-ulcer
roids in this disorder remains contro- syndrome
versial. Cigarette smoking may in-
developing duodenal ulcers compared crease the incidence of gastric ulcers
with those who have types A, B, and as well as decrease healing and in- present as medical emergencies, with
AB. Secretors of blood group an-

crease recurrence. However, no direct perforation or hemorrhage. Males and
tigens (presence of ABO blood group evidence links smoking to gastric females are affected equally, and duo-
antigens in body fluids such as sa- ulcer formation. There is no defini- denal and gastric ulcers are distrib-
liva) have a 50% increase in risk for tive evidence suggesting that psycho- uted equally.
developing duodenal ulcers compared logic factors, such as stress or anxi- Cushing ulcers commonly develop
with nonsecretors. Patients who have ety, lead to gastric ulcers. Genetic after cerebral trauma or neurosurgery,
blood group type 0 and are secretors risk factors associated with gastric usually within 1 week of the insult.
have a 150% increase in risk for de- ulcer disease include blood type A They are associated with gastric acid
veloping duodenal ulcers. This may and first-degree relatives who have hypersecretion and present with acute
be related to a propensity in these gastric ulcers. bleeding. Curling ulcers are seen
patients to develop problems with commonly with burns, classically
H pylon (see Pathophysiology). occurring 2 weeks after the initial
Multiple disease processes are as- SECONDARY PEPTIC insult. If they occur within 2 days of
sociated with an increased incidence ULCERATION the burn, they are found in the duo-
of peptic ulcer disease (Table 3). Primary peptic ulcers usually are duo- denum. Ulcers occurring later tend to
Several factors explain these associa- denal, but secondary peptic ulcers develop in the gastric fundus.
tions, including gastrointestinal (GI) can be duodenal or gastric. Ulcer- Ulceration due to NSAID inges-
tract involvement in the primary dis- ation is associated with stress, such tion, like stress ulcers, often are si-
ease process (eg, Crohns disease) or as critical illness. The risk factors for lent until complications develop (Fig-
altered reparative mechanisms in the the development of stress ulceration ure 2). They tend to occur in patients
stomach or duodenum due to the un- are well-defined. The most common receiving long-term NSAID therapy;
derlying disease or treatment of the finding-superficial fundal lesions- however, there is an idiosyncratic
underlying disease (NSAIDs and ste- occurs rapidly and almost universally reaction to ASA that can lead to
roids in autoimmune diseases). following surgery or major trauma. acute ulceration and hemorrhage after
Their formation has been related to the first dose.
Gastric Ulcers one or a combination of three factors: Zollinger-Ellison syndrome is asso-
Primary gastric ulcers occur on the 1) decreased mucosal blood flow, ciated with the formation of multiple
border zone between the parietal cell 2) disruption of the mucosal barrier, ulcers. High levels of circulating gas-
area and pyloric mucosa and often or 3) intraluminal acidity. Stress ul- trim are present due to hypersecretion
are associated with decreased stom- cers account for 80% of the peptic from a gastrinoma. This disorder is
ach acid (Figure 1). They are rare, disease seen during infancy and early extremely rare in children, but should
occurring seven times less commonly childhood. They are associated with be suspected in any child who has
than duodenal ulcers in children and shock, respiratory failure, sepsis, hy- multiple ulcers of the stomach, duo-
four times less commonly in adults. poglycemia, severe burns (Curling denum, or jejunum.
The exact incidence of primary gas- ulcer), and intracranial lesions (Cush- Infectious agents have been found
tric ulcers in the United States is un- ing ulcer). These ulcers usually in association with gastric ulcers,

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 #{149}
#{149} #{149}
#{149}#{149}
#{149} #{149} GASTROENTEROLOGY #{149}

Peptic Ulcers

TABLE 3. Conditions Associated With Increased Incidence of

Peptic Ulcer Disease
#{149}
Alpha-l-antitrypsin deficiency

#{149}
Cystic fibrosis

#{149}
Phenylketonuna

#{149}
G6PD deficiency

#{149}
Hyperparathyroidism (increased calcium increases gastric secretion)

#{149}
Sickle cell anemia (about 7% to 8% have peptic ulcers) FIGURE 1. Primary gastric ulcer on the
lesser curvature of the stomach iti an
#{149}
Cirrhosis of the liver 8-month-old white female who presented
with hematemesis.
#{149}
Hypergastrmnemia
Zollinger-Ellison syndrome
Antral 0 cell hyperplasia or hyperfunction

#{149}
Renal failure, especially after renal transplant or with hemodialysis

#{149}
Chronic obstructive pulmonary disease

#{149}
Polycythemia vera

#{149}
Crohn disease

#{149}
Chronic pancreatitis

#{149}
Collagen-vascular disease (eg, dermatomyositis)

#{149}
Diabetes mellitus

especially cytomegalovirus and I billion parietal cells in the middle FiGURE 2. Large gastric ulcer with
heaped-up tnargins on the greater
H pylon. The significance of these zones of gastric glands located in the
curvature of the stomach in a 14-year-old
findings is unclear. body and fundus of the stomach.
boy who ingested large amounts of
There are three phases of gastric acid NSA JDS and presented with hematemesis.
secretion: cephalic, gastric, and intes-
Gastric Physiology and tinal. In the cephalic phase, sight, fists to suppress virtually all modes
Pathophysiology
taste, smell, and especially the of gastric acid secretion stimulation
A description of normal gastric phys- thought of food stimulate acid secre- underscores the central regulatory
iology is essential to understanding tion from the parietal cells through role of histamine. Acetylcholine, a
the mechanisms that underlie the de- vagal activity. The gastric phase of neurotransmitter originating in post-
velopment of peptic ulceration. stimulated acid secretion is initiated ganglionic neuroeffector cells in the
Pathophysiologic events that lead to by ingestion of food, fundus and stomach, is released by vagal stimu-
disruption of the gastric or duodenal body distension, and by specific food. lation of the parietal cell. Vagal ac-
mucosa can be divided into offensive In the intestinal phase, gastrin release tivity contributes largely to the spon-
and defensive factors (Table 4). Of- occurs after gastric contents enter the taneous secretion of acid in the unfed
fensive factors increase acid or pep- proximal small bowel. This, in turn, or basal state. Vagotomy markedly
sin secretion; defensive factors reflect stimulates gastric acid secretion. reduces the gastric acid response to
the hosts ability to protect itself Stimulation of acid secretion by fundic distension and basal acid se-
from the harmful effects of the offen- the gastric parietal cell is controlled cretion. It also reduces the maximal
sive factors. largely by the action of three potent acid response to exogenous histamine
secretagogues: histamine (paraendo- or pentagastnin by about 60%. Gas-
crime), acetylcholine (neuroendo- trim release from 0 cells in the
OFFENSIVE FACTORS
crine), and gastrin (endocrine) (Fig- antrum, pylorus, and duodenum is
Gastric Acid ure 3). Histamine, found in mast cells stimulated largely by peptides and
Gastric acid secretion begins in the in the lamina propria of the stomach, amino acids in the antral lumen and
human infant on the first day of life. stimulates cyclic adenosine mono- suppressed when the antral pH is less
Maximal acid secretion expressed per phosphate production within the pan- than 3.0. Gastrin is a potent stimulant
weight increases until 3 to 4 months etal cell. Cholinergics and gastrin of gastric acid secretion, but only a
of age, when it approaches adult val- increase intracellular calcium. The moderate stimulant for secretion of
ues. Acid is secreted by more than ability of gastric H2 receptor antago- pepsinogens.

Pediatrics in Review Vol. 16 No. 7 July 1995 259

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 GASTROENTEROLOGY
Peptic Ulcers

increased risk for duodenal ulcer. superficial epithelial cells and mucus
TABLE 4. Offensive Versus P01 levels are elevated significantly cells on glands throughout the stom-
Defensive Factors in the in patients who have gastninoma. In ach. The release of mucus is stimu-
Formation of Peptic Ulcers family members of patients who have lated by cholinergic agonists, prosta-
primary ulcer disease, PGI levels glandins, and inflammatory/immune
#{149}
OFFENSIVE DEFENSIVE
greater than 130 j.ag/L may signify cytokines. The mucus layer in the
Acid Extraepithelial the development of duodenal ulcers. stomach is approximately 10 to 20
Pepsin -Mucus PGII, produced in the antrum, pylo- times the thickness of the surface
Gastrin -HCO3 rus, and Brumner glands of the duo- epithelial cells and is full of charged
Drugs -Hydrophobic denum, often is elevated in antral protein particles. Therefore, acid dif-
Hpylori layer gastritis. Serum concentrations of PG. fuses three to four times slower
? Bile acids Epithelial measured by radioimmunoassay, cor- through mucus than water, making
-Cell turnover relate with maximal acid secretory the mucus layer an effective barrier
-Prostaglandins capacity, indicating an association to the deleterious effects of stomach
Subepithelial with secretory mass of parietal cells acid.
-Blood flow and chief cells.
-HCO3 Bicarbonate
Infections Bicarbonate secretion by surface epi-
H pylon is a unipolar, multiflagellate, thelial cells, mediated by active chlo-
spiral organism that has been associ- ride/bicarbonate exchange, provides
The proton pump of the parietal ated with gastritis in adults and, to a another buffer to the potentially
cell is the final common pathway for lesser extent, in children. It is almost harmful effects of gastric acid. Gas-
histamine-, acetylcholine-, or gastrin- universally present in the stomachs of tric bicarbonate secretion is stimu-
induced acid secretion (Figure 3). adult patients who have duodenal lated by prostaglandins E2 and F2,
Potassium and chloride ions are ulcers and has been implicated in the cGMP, cholecystokinin, and calcium.
transferred from the cytoplasm of the genesis of peptic ulcer disease in a Inhibitors to gastric and duodenal
parietal cell to secretory canaliculi large number of patients. H pylon mucosal excretion include aspirin,
and then to luminal fluid. A unique also has been shown to attack cells NSAIDs, and acetazolamide. Hydro-
proton pump (H/K-ATPase) ex- with surface antigens from blood chlonc acid diffuses toward the mu-
changes one hydrogen ion (H) from group 0 preferentially, which could cosa and is slowed in the mucus
the cytoplasm. This hydrogen ion is explain the increased incidence of layer, then neutralized by the bicar-
derived from water within the pan- peptic ulcer disease in patients who bonate secreted from surface epithe-
etal cell. For each hydrogen ion se- are of this blood group. Although hal cells. This produces a pH gradi-
creted, a bicarbonate ion is produced several theories have been proposed ent, with decreasing acidity on the
within the cell. Bicarbonate ions then to explain the effect of H pylon in epithelial cell surface (and, therefore,
are exchanged for chloride ions at the the development of peptic ulcer dis- less potential harmful effects of acid)
basolateral membrane and secreted ease, its exact role is unclear. It has and increasing acidity in the gastric
into the gastric lumen along with W been suggested that the inflammatory lumen (where acid is important in
ions by the parietal cell. response induced by digesting food).
H pyloni disrupts ___________
Pepsins
mucosal defenses.
All agents that stimulate acid secre- Toxin production by Parltalc&I
tion stimulate pepsin secretion. Pep- H pyloni may dam-
sins are enzymes present in gastric age the mucosa di-
juice that hydrolyze protein at a pH rectly. For further
1f-.-Proton pump
less than 5 but are inactivated irre- information, the
versibly at alkaline pH. They digest reader is referred to
gastric mucus glycoproteins, lipopro- several excellent
teins, collagen, and elastin. Pepsins reviews on H pylon
cyclase - cAMP secretion
are secreted from the chief cells as published in the Histamine Adenylate -.--- Acid
pepsinogens and are converted to Gastnoentenology
active pepsins by gastric acidity. Clinics of Nonth Calcium
There are two immunochemically Amenica (see Sug-
distinct types of pepsinogen (PG): gested Readings).
PGI and PGII. PGI is the major hu-
man pepsinogen; its presence
ited to chief cells and mucous
is lim-
neck Acetchohne
I
DEFENSIVE (vagal stimulation)
cells in the fundic mucosa. Serum
FACTORS
PGI concentrations are elevated in
Mucus
30% to 50% of patients who have a FIGURE 3. Schematic representation of gastric acid
duodenal ulcer. A serum level of PG A thick mucus gel production by the panietal cell. Used with permission from
above 130 pgIL imparts a threefold is secreted from Contemporary Pediatrics.

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 GASTROENTEROLOGY
Peptic Ulcers

Prostaglandins GASTRIC ULCERS ulcer pain can be exacerbated by

Prostaglandins E2 and F, facilitate The underlying mechanism of gastric acidic food or beverages such as
mucosal defense via a cytoprotective ulceration is poorly understood. Be- soda, juices, pickles, vinegar, toma-
effect on gastric mucosa. They inhibit cause most of these ulcers occur on toes, alcohol, and spices. No clinical
parietal cell function directly, thereby the lesser curvature of the stomach at features or symptoms can differenti-
decreasing acid secretion. They also or near the antral side of the junction ate gastric from duodenal ulcers
increase production of bicarbonate of the oxyntic and antral mucosa, it reliably.
and mucus and enhance mucosal is postulated that the blood supply to Symptoms of peptic ulcer disease
blood flow (which is critical in the this area is less luxurious, which may in children tend to differ, depending
ongoing reparative process of gastric affect protective factors adversely and on the age of presentation; the older
mucosal epithehium). lead to an increased frequency of the patient, the more the symptoms
ulceration. Several other factors may approach the pattern seen in adults.
contribute to the formation of gastric Infants who have peptic ulcer disease
ulcers. Motility defects, such as in- present with poor feeding, gastroin-
Mechanisms of Ulcer competence of the pylonic sphincter, testinal bleeding, gastric or intestinal
Formation might allow duodenal contents to perforation, or simply vomiting. Tod-
reflux into the stomach. Duodenal dlers and preschoolers present with
DUODENAL ULCERS poorly localized abdominal pain,
reflux of substances such as bile ac-
Duodenal ulcers are caused when ids, lysolecithin, and pancreatic Se- vomiting, or gastrointestinal bleeding.
offensive factors overwhelm protec- cretions may damage the gastric mu- Older children and adolescents have
tive defensive mechanisms; the old cosa or disrupt the mucosal barrier, poorly localized epigastnic or even
adage of no acid, no ulcer, seems allowing back diffusion
of hydro- right lower quadrant pain. The pain
to apply. Therefore, parietal cell se- gen ions into the mucosa. Patients can occur sporadically, cycling with
cretion of gastric acid is important in who have gastric ulcers may have periods of remission for weeks or
formation of duodenah ulcers. One delayed gastric emptying, leading to months. The response of the pain to
measure of parietal cell function is stasis and delayed clearing of re- eating in these patients varies.
maximal acid output (MAO), the fluxed duodenal contents or retained In one study of I 10 children who
amount of acid secreted by the stom- food particles. Retained food particles had a duodenal ulcer, the mean age
ach within 1 hour of a maximally continually stimulate gastrin release, at diagnosis was I 1.3 years; 46% had
effective exogenous stimulus (penta- resulting in increased production of some symptom of peptic ulcer dis-
gastrin, a synthetic analogue of gas- acid. ease manifested prior to I 0 years of
trim, typically is used). Increased age. It is estimated that up to 90% of
MAO is the physiologic abnormality patients who have duodenal ulcers
implicated most frequently in chil- have abdominal pain, 37% have me-
dren who have duodenal ulcer dis- Clinical Features of Peptic lena, 10% have vomiting, and 5%
ease, although some studies fail to Ulcer Disease have hematemesis on initial presenta-
confirm this finding. Abnormalities in tion. Of note is that a small percent
basal acid output, the amount of acid PRESENTATION (7%) of children who have functional
secreted during 1 hour in the absence Symptoms in patients who have pri- abdominal pain report pain occurring
of a specific stimulus, have not been mary peptic ulcer disease tend to wax at night compared with more than
found to be useful clinical indicators. and wane. The classic presentation of 60% of patients who have peptic ul-
Evidence is increasing that acid duodenal ulcers in adults is gnawing cer disease being awakened by pain.
secretion by the parietal cell may or burning epigastric pain, similar to Most primary ulcers in children less
have less to do with peptic ulcer for- hunger pains, occurring 1 to 3 hours than 6 years of age are gastric and
mation than originally thought, and after eating. The pain may awaken affect boys and girls equally. In those
other factors such as blood flow may the patient from sleep. Because the more than I 0 years of age, the major-
be important. Several alternative the- pain is relieved by food, ulcer pa- ity of ulcers are duodenal and found
ories about the formation of peptic tients may gain weight because eat- in boys. Secondary peptic ulcers tend
ulcers are being investigated, al- ing makes them feel better. Other to present acutely with complications
though no conclusive evidence has features commonly noted in adult of peptic ulcer disease such as he-
been demonstrated. One interesting patients who have duodenal ulcer matemesis, perforation, penetration,
theory suggests that the immune cells disease include heartburn, hypersali- or obstruction (Table 5).
in the lamina propnia, not parietal vation, nausea, vomiting, bloating,
cells, are the ones that respond to H, abdominal distension, and intolerance
antagonists and, therefore, are of pri- to fatty foods. DIFFERENTIAL DIAGNOSIS
mary importance in peptic ulcer for- Only 50% of patients who have Numerous disorders, both functional
mation. This theory highlights the primary gastric ulcers report relief by and organic, present similarly to pep-
importance of understanding the pri- eating, and in some, food will aggra- tic ulcer disease: functional abdomi-
mary events leading to ulcer forma- vate the symptoms. Those who have nal pain, gastritis, giardiasis, acute
tion so as to target future medications gastric ulcers often have nausea, gastroentenitis, esophagitis, metabolic
appropriately for the treatment of vomiting, and weight loss (infrequent acidosis, inflammatory bowel disease,
peptic ulcer disease. in duodenal ulcer). Typical gastric irritable bowel syndrome, ureteropel-

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I GASTROENTEROLOGY
#{149}#{149}#{149}#{149}

screening. In experienced hands, doc-

TABLE 5. Presentation of Peptic Ulcer Disease in Children: umentation of an ulcer crater in the
Primary Versus Secondary Lesions stomach or duodenum is sufficient to
establish the diagnosis of peptic ulcer
SECONDARY PEPTIC #{149}

SYMPTOMS PRIMARY PEPTIC ULCER ULCER disease in children. However, spasm

of the bulb, pylorospasm, or delayed
Abdominal pain 80% of patients Often absent j gastric emptying are nonspecific find-
ings in children and do not establish
Vomiting 25% of patients-in children Often absent #{149}
the diagnosis of peptic inflammation.
less than 4 years, it may be #{149}
Who, then, should undergo upper
a presenting complaint, #{149}
endoscopy? Several symptoms are
unrelated to meals, and
highly suggestive of the diagnosis of
does not relieve pain; in : peptic ulcer disease in children:
older children, vomiting I
1) presence of pain in the epigas-
often follows meals, and #{149}
trium, 2) pain related to eating,
50% of time it relieves pain
3) family history, 4) vomiting, and
Nausea 20%-usually older children; Often absent #{149} 5) GI bleeding. Although the sensi-
not presenting complaint #{149} tivity of each of these factors has
been shown to be more than 70%,
01 bleeding Present up to 60% of time; Primary complaint in up their specificity has been as how as
may not be primary to 80% of patients 45%. In one study, no symptom or
complaint group of symptoms could predict ad-
Perforation Absent initially Primary complaint equately (with reasonable sensitivity
and specificity) which patient suf-
Weight loss Present in 25% of patients Often absent I fered from peptic ulcer disease. En-
who have gastric ulcers doscopy was considered in any pa-
tient who had any positive responses.
Obstruction Absent initially Primary complaint
Any child less than 4 years of age
who has intermittent vomiting and/or
abdominal pain for more than
vic junction obstruction, appendicitis, upper GI series has been the initial 4 weeks should be evaluated because
pancreatitis, parasitic infestation, bihi- screening test of choice; this will functional abdominal pain is far less
ary tract disease, colitis, diabetes identify peptic ulcer disease correctly common in this age group. In gen-
melhitus, eosinophihic gastroenteritis, in more than 50% of patients. Dou- eral, pediatric patients should be con-
heavy metal toxicity, anaphylactoid ble-contrast studies (where an effer- sidered candidates for evaluation of
purpura, Meckel diverticulum, pyelo- vescent substance is given in addition peptic ulcer disease by upper endos-
nephritis, and spinal cord lesions. to barium to create an air contrast copy if they have chronic abdominal
study) improve the diagnostic capa- pain (>3 months) or pain that causes
bihity of upper GI series to chose to significant discomfort and any of the
DIAGNOSTIC EVALUATION 90%; however, these studies are diffi- following: 1) hematemesis; 2) a his-
As always, a complete history and cult to perform in children. Investiga- tory of peptic ulcer disease in a first-
physical examination are the most tions have demonstrated that up to degree relative; 3) nocturnal pain,
important parts of the initial evalua- 63% of children thought to have pep- especially if it awakens the patient
tion. Historical points that should tic ulcers according to radiographic from sleep; 4) pain occurring within
raise the suspicion of peptic ulcer findings had normal endoscopic 1 hour of eating or relieved by eat-
disease include a family history of findings. ing; 5) recurrent vomiting; 6) weight
peptic ulcer disease, classic pattern of In adults, endoscopy is reserved loss; and 7) chronic complaints local-
pain and related symptoms, predis- for patients who have: I ) persistence ized to the epigastrium (especially in
posing factors such as smoking or of symptoms despite adequate then- children > 10 years of age).
regular use of NSAIDs, long-term apy, 2) nondiagnostic upper 01 series Additional studies in patients who
corticosteroid therapy (controversial), and persistent symptoms, 3) coexist- have peptic ulcer disease can help
nocturnal pain, and past or present ent GI bleeding, 4) coexistent gastric uncover an underlying predisposition
conditions associated with peptic ul- outlet obstruction, 5) recurrent duode- to peptic ulcer formation. A fasting
cer disease (Table 3). Findings on nal ulcer and scarring, 6) previous serum gastnin level is obtained to
physical examination of patients who ulcer surgery, and 7) only gastric exclude Zolhinger-Ellison syndrome,
have peptic ulcer disease can be nor- ulcers (because of the potential for a condition of hypergastrinemia and,
mal, but commonly epigastnic tender- malignancy). There are no clear therefore, acid hypersecretion due to
ness and occasionally guaiac-positive guidelines to delineate which pediat- the presence of a gastrinoma. Gastrin
stools are found. ric patients should undergo endos- levels are significantly elevated, usu-
The diagnosis of peptic ulcer dis- copy for evaluation of peptic ulcer ally greater than 500 pg/mL and of-
ease is confirmed by either radiologic disease. An upper 01 series tradition- ten in the thousands (normal, 0 to
or endoscopic studies. In adults, an ally has been used in their initial 200 pg/mL). Zohlinger-Elhison syn-

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 GASTROENTEROLOGY
Peptic Ulcers

drome is rare in children but should and hypercalcemia with nephrocalci- acid secretion. H2 antagonists inhibit
be suspected when there are multiple nosis may be seen in patients who responses to all secretagogues (see
duodenah or gastric ulcers, recurrent ingest calcium preparations. Many of Pathophysiology) and are quite effec-
ulcers despite therapy, hypercalcemia, the antacids used combine the two tive in suppressing gastric acid. H2
a family history of ulcers, a family anions magnesium and aluminum, antagonists are reversible, competi-
history of endocrine tumors, unex- thereby diminishing side effects. As tive antagonists of the action of hista-
plained diarrhea, or if contemplating with all antacids, these preparations mine on H2 receptors and are highly
surgery for ulcers. A secretin stimula- can interfere with absorption of other selective. They function in a dose-
tion test, in which patients receive medications if they are administered dependent manner, decreasing both
intravenous secretin and serum gas- within 30 to 45 minutes of the antac- the volume of gastric juice secreted
tnin samples subsequently are ob- ids. The cost of a 6-week course of and the amount of gastric acid. H2
tamed over time, can be used to con- antacid therapy is approximately $60, antagonists are indicated for short-
firm Zolhinger-Elhison syndrome. A about 25% to 50% the cost of H2 term therapy of peptic ulcer disease,
serum calcium level should be ob- antagonists or proton pump inhibitors. prevention of recurrences, and treat-
tamed at the same time as a serum Pediatricians comfortable using ment of Zolhinger-Ellison syndrome
gastrin level to evaluate patients for antacids should consider empiric and reflux esophagitis.
multiple endocrinopathy type I. therapy with these drugs in patients Cimetidine was the first medication
who have food-related abdominal of this class marketed. The pediatric
pain when the pain is not associated dose is 7 mg/kg, given every 6 to 8
Treatment with systemic signs of illness such as hours. Side effects of all H2 antago-
In adults, the natural history of peptic weight loss or fevers. If the patient nists include nausea, headache, and
ulcer disease suggests that 15% to does not respond to this medication skin rash. In addition, cimetidine in-
40% of ulcers will heal spontane- within 2 weeks, then referral to a terferes with other medications me-
ously in 2 to 4 weeks. However, the pediatric gastroenterologist should be tabolized by the cytochrome P450
1-year recurrence rate of duodenal considered. If the patient responds to system and rarely can cause gyneco-
ulcer is 50% to 80% in untreated pa- this intervention, then treatment for a mastia as well as impotence. Raniti-
tients, as well as in patients who total of 8 weeks is warranted. If pain dine and nizatidine are four to 10
have H pyloni in whom this organism recurs after completion of therapy, times as potent as cimetidine and
has not been eradicated. Therefore, it referral to a pediatric gastroenterolo- tend to cause fewer side affects and
is imperative that appropriate therapy gist should be considered again. minimal inhibition of the cytochrome
be prescribed. P450 system. Published pediatric ex-
penience with ranitidine is consider-
AGENTS THAT BLOCK ACID able. The dosage commonly used is
ACID NEUTRALIZATION SECRETION 2 to 3 mg/kg given every 8 to
The first use of antacids was ascribed H2 receptor antagonists are one of the 1 2 hours, with infants being treated
to the Sumerians who, in approxi- most frequently used medications for on an every 8 hours schedule and
mately 3500 BC, used alkaline sub- treating peptic inflammation. H2 re- older children every 12 hours. Famo-
stances such as mint and peppermint ceptors are found on the gastric acid- tidine is an H2 antagonist that is 20
leaves to neutralize gastric acidity producing panietal cells, and hista- times stronger than cimetidine and
and treat indigestion. Antacids are a mine serves as a common pathway can be given once a day. The adult
well-studied, low-cost, safe, and ef- for a variety of stimulants to gastric dose is 40 mg/day, but there is less
fective means of treating peptic in-
flammation. They neutralize gastric
acid, thereby preventing the deleteri- TABLE 6. Dosage of Medications Used in Peptic Ulcer Disease
ous effects of stomach acid on nor-
mal and eroded gastric mucosa. Ant- MEDICATION PEDIATRIC DOSAGE ADULT DOSAGE
acids are indicated for patients of any Antacids 0.5 mL/kg/dose 1 h 1-2 Thsp 1 h after meals
age to treat peptic ulceration. The after meals and QHS and QHS
preferred product is the liquid prepa-
ration; the dose used in pediatrics Cimetidine 7 mg/kg/dose q 6-8 h 300 mg qid or 800 mg QHS
(Table 6) is 0.5 mL/kg, given 1 and rid or qid or 15 mg/
3 hours after eating and before bed. kg/dose q 12 h bid
Because of the need for frequent ad-
Ranitidine 1-2 mg/kg/dose q 150 mg bid or 300 mg QHS
ministration, compliance is a major
8-12 h bid or tid
issue in treating patients with
antacids. Famotidine ? 40 mg QD
The side effects of antacids are
related to the cations present; diar- Omeprazole ? 20 mg QD
rhea occurs in those who receive the Sucralfate ? 1000 mg qid
magnesium-containing preparations,
constipation occurs in patients who Misoprostol ? 200 g qid
receive the aluminum preparations, =j
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 #{149}
GASTROENTEROLOGY #{149}
#{149}
Peptic Ulcers

published experience with pediatric NSAIDs. Misoprostol must not be sewing of the peptic ulcer. The initial
use of this medication than with used by patients who are or possibly symptoms recur in 50% to 75% of
ranitidine. could be pregnant. Its use may cause pediatric patients, more commonly
The proton-pump inhibitor omepra- miscarriage or incomplete miscar- with duodenal than gastric ulcers.
zole works by inhibiting the hydro- riage, which could lead to infertility, There are no reliable predictors to
gen ion pump in the panietal cell, significant hemorrhage, or death. determine whose disease is most
thereby blocking the final common Misoprostol is given at a dose of likely to occur.
pathway for acid formation. This 200 g qid in adults; once again, Hemorrhage accompanies peptic
drug is indicated in pathologic hyper- there is little published experience in ulcer disease approximately 1 5% to
secretory states such as Zollinger- pediatric patients. 20% of the time, more commonly
Elhison syndrome. Omeprazole is be- with duodenal than gastric ulcers and
coming the drug of choice for reflux more frequently with secondary than
esophagitis in adults. The adult dose ANTIINFECTIVE AGENTS
primary ulcers. Bleeding stops spon-
is 20 mg/day; however, there is little The successful treatment of peptic taneously in 90% of these patients,
published experience in pediatrics. ulcers and gastnitis associated with although the risk of rebleeding in
This drug is well tolerated, although H pyloni requires eradication of this duodenal ulcers is 40%.
reported side effects include head- microorganism by the use of standard Perforation, defined as an exten-
ache, nausea, and abdominal pain. antimicrobials combined with bis- sion of the ulceration through the
muth preparations. Therefore, it is serosa into the peritoneal cavity, oc-
important to consider and confirm curs in 5% to 10% of patients who
CYTOPROTECTIVE AGENTS this diagnosis. Although optimal have peptic ulcer disease. These ul-
Sucralfate is a sulfated disaccharide treatment has not yet been defined, cers often are on the anterior wall of
aluminum salt that splits into nega- several studies have shown efficacy the duodenum, in the first portion, or
tively charged aluminum plus other following a course of bismuth subsa- on the lesser curvature of the stom-
component particles when ingested. licylate in combination with one or ach. About 75% of patients who have
These particles become attracted to two antibiotics, either amoxicilhin perforation have a history of peptic
the positively charged protein mole- and/or metronidazole ( triple thera- ulcer disease. Right shoulder pain
cules of injured gastric mucosa with py ). Because a low frequency of may be the most notable symptom
a six to eight times greater affinity antimicrobial resistance among the initially, but this depends on the loca-
than to normal gastric epithelium. It H pyloni is found in children and an tion of the perforation.
serves, therefore, to coat
damaged increased frequency of side effects is Penetration occurs when peptic
gastric mucosa, insulating it and pro- associated with triple therapy, most ulceration extends through the serosa
tecting it from further damage by authors recommend a 4- to 6-week into surrounding structures that seal it
acid, pepsin, or bile. Sucralfate is course of bismuth and a 2- to 4-week off, such as the penitoneum, pancreas,
indicated for the treatment of gastric course of amoxicilhin to eradicate H hepatobihiary tract, or colon. Penetra-
or duodenal ulcers, but must be given pyloni. Amoxicillin is used in a stan- tion should be suspected in the pres-
as a slurry (1 g/lO mL) to affect the dard dosage (20 to 40 mg/kg per day ence of constant lumbar pain and
esophagus. The adult dose is a 1-g tid). The dose of bismuth is 15 mL intractability to medical regimens.
tablet qid; this can be titrated down (one tablet) qid in children 10 to Gastric ulcers on the posterior wall
for use in pediatric patients. Sucral- 12 years and 30 mL qid (two tablets) may penetrate to the pancreas; ulcers
fate is an extremely potent phosphate in children older than I 2 years. Most on the lesser curvature or anterior
binder and may cause constipation as authors do not recommend long-term wall rarely penetrate.
well as problems with absorption of treatment of children less than Gastric outlet obstruction occurs
other drugs administered within 1 hour 10 years of age with bismuth subsa- with chronic peptic disease and im-
of sucralfate. hicylate because of the potential tox- plies complete or partial obstruction
Prostaglandins are 20 carbon fatty icity (eg, renal impairment) and prob- of the distal stomach, pylorus, or
acids that exert various physiologic lems associated with chronic exposure proximal duodenum. It may result
effects. The E type, such as synthetic to salicylates. from edema or scarring and presents
misoprostol, exerts a trophic effect on with vomiting, often late in the day
gastric epithelium by increasing or in the evening. Pain is described
blood flow and bicarbonate secretion Complications of Peptic as constant and associated with post-
and markedly increases production of Ulcer Disease prandial fullness.
mucus. Prostaglandins also provide Prior to the routine use of H2 antago-
an antisecretory effect by blocking nists, up to 33% of patients who had
the rise in cAMP induced by hista- peptic ulcers eventually required sur- Conclusion
mine, thereby inhibiting the forma- gical management of their disease or Peptic ulcer disease is an uncommon
tion of gastric acid by the panietal its complications. Recurrence is the pediatric disorder that may have sig-
cell. Misoprostol is indicated in the most common complication of peptic nificant long-term ramifications. The
treatment of gastric or duodenal ul- ulcer disease. A small percentage of significance of peptic ulcer disease
cers and is particularly useful in pre- patients eventually are defined as likely will increase as more inten-
venting the gastric inflammation having intractable disease and un- sively ill children survive their hospi-
caused by the chronic use of dergo selective vagotomy and over- tal stay and develop secondary ulcers.

264 Pediatrics in Review Vol. /6 No. 7 July /995

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#{149} : .#{149} #{149} #{149} #{149}#{149}#{149} #{149} #{149} GASTROENTEROLOGTY#{149}
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#{149}

It also is a disease that has impor-

tance for the primary care physician, PIR QUIZ
who will be called on to identify 9. Assuming that no additional risk 12. An I 1-year-old boy has had epigas-
those children at risk for these disor- factors are present, among the pa- tric pain for the past 4 months. The
ders among the many patients pre- tients listed, the one at greatest risk pain frequently awakens him at
for developing a duodenal ulcer is: night. Results of an upper gastro-
senting with abdominal pain, weight
A. A 10-year-old boy who requires intestinal series were normal. The
loss, or vomiting. Consultation with a an occasional prednisone most appropriate next diagnostic
pediatric gastroenterologist is encour- pulse to control seasonal exac- step is:
aged to facilitate confirmation of the erbations of asthma. A. Double-contrast upper gastroin-
diagnosis, which will aid in the B. A 10-year-old boy whose father testinal series.
has been diagnosed as having a
choice of appropriate therapy. B. Fasting serum gastrin level.
duodenal ulcer.
C. Repeat conventional upper gas-
C. A 13-year-old boy who drinks
trointestinal series.
alcohol at weekend parties.
SUGGESTED READING D. Therapeutic trial of omeprazole.
D. A 13-year-old girl who smokes
E. Upper gastrointestinal endos-
Do()ley CP, Cohen H, ed. Helicohacter pylon one half pack of cigarettes
copy.
infection. Gastnoenterol Clin N Amer. 1993; daily.
22:1-206 E. A 13-year-old girl who takes Match each listed therapeutic agent
Fontana M, Tornaghi R, Petrillo M, Ct al. ibuprofen monthly for primary
with its appropriate mechanism of
Ranitidine treatment in newborn infants. dysmenorrhea.
action and indication for use in the
J Pediatr Gastnoentenol Nutr. 1993; 16:406-
10. A correct statement about the prevention and/or treatment of pep-
411
pathophysiology of peptic ulcer tic ulcer
Kato 5, Shibuya H, Hayashi Y, et al. Effec-
disease is that: 13. Augments blood flow, bicarbonate
tiveness and pharmacokinetics of
omeprazole in children with refractory A. Extracellular calcium plays no secretion, and gastric mucus pro-
duodenal ulcer. J Pediatr Gasinoenterol significant role. duction; prolonged NSAID use
B. Gastrin inhibits gastric acid se- 14. Bactericidal; documented H pylon
Nutr. 1992;l5:l84-l88
Rosioru C, Glassman MS. Berezin SH, et al. cretion. infection
Treatment of Helicohacter pylon-associated C. Helicobacten pylon preferen- 15. Binds preferentially to injured mu-
tially attaches to duodenal epi- cosa; prevention of further injury
gastroduodenal disease in children. Dig Dis
thelial cells. 16. H2 receptor antagonist; failure of
Sci. I 993;38: 123-I 28
D. Histamine acts directly on the
adequate response to antacid
parietal cell proton pump.
therapy
E. Prostaglandin E2 stimulates gas-
17. Proton pump inhibitor; Zollinger-
tric mucus production.
Ellison syndrome
I I. A 4-year-old child who has a pri- A. Bismuth
mary duodenal ulcer is most likely B. Misoprostol
to present having: C. Omeprazole
A. Epigastric pain. D. Ranitidine
B. Intestinal perforation. E. Sucralfate
C. Intolerance to fatty foods.
D. Lost weight.
E. Recurrent vomiting.

Pediatrics in Review to Hold 1996

Cover Art Contest: Works by Children!
In 1996, we plan to display a piece child/adolescent artist) doing Pediatricians: Please have your
of art by children on the covers of your favorite thing. patients send art they would like
our 1996 issues. Four pictures will 3. Qualification: The artist must be considered to:
be chosen, and the cover artwork either between the ages of a) 5
Sydney Sutherland,
will be changed quarterly. and 10 years or b) I I and 15
years. (There will be two cate-
Editorial Assistant
Rules of the Contest Pediatrics in Review
gories, by age, for submission
I . The contest will run from Janu- and judging.) do The Department of
ary through July 1995. (Winners 4. Requirements: The picture must Pediatrics, Box 777
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2. The theme of each submission: ARTISTS: Think Big! Small Rochester, NY 14642
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Pediatrics in Review Vol. /6 No. 7 July 1995 265

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 Peptic Ulcer Disease in Children
Adam G Mezoff and William F Balistreri
Pediatrics in Review 1995;16;257
DOI: 10.1542/pir.16-7-257

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 Peptic Ulcer Disease in Children
Adam G Mezoff and William F Balistreri
Pediatrics in Review 1995;16;257
DOI: 10.1542/pir.16-7-257

The online version of this article, along with updated information and services, is located on
the World Wide Web at:
http://pedsinreview.aappublications.org/content/16/7/257

Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned, published, and
trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove
Village, Illinois, 60007. Copyright 1995 by the American Academy of Pediatrics. All rights reserved.
Print ISSN: 0191-9601.

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