Transcript Peptic Ulcer Disease

PEPTIC
ULCER
DISEASE
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The lesion of peptic ulcer disease (PUD) is a disruption in the
mucosal layer of the stomach or duodenum. An ulcer is
distinguished from an erosion by its penetration through the
muscularis mucosa or the muscular coating of the gastric or
duodenal wall. Peptic ulcer disease results from the
imbalance between defensive factors that protect the mucosa
and offensive factors that disrupt this important barrier.
Mucosal protective factors include the water-insoluble
mucous gel layer, local production of bicarbonate, regulation
of gastric acid secretion, and adequate mucosal blood flow.
Aggressive factors include the acid-pepsin environment,
infection with Helicobacter pylori, and mucosal ischemia.
Many differences are noted between children and adults with
peptic ulcer disease, especially in clinical presentation, in the
prevalence rates of different types of ulcer disease, and the
prevalence rate of complications.
PATHOPHYSIOLOGY
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The 2 most important concepts in understanding the
pathophysiology of peptic ulcer disease in children are the
host factors that serve to protect the GI mucosa from
ulceration and the inflammatory mediators and aggressive
factors that contribute to mucosal inflammation and
ulceration.
Peptic ulcer disease in children is the result of an imbalance
between mucosal defensive and aggressive factors. An
overlying physiochemical barrier provides cytoprotection of
the gastric mucosa. This barrier comprises water-insoluble
gastric mucus, gastrically produced bicarbonate, an
unstirred water layer, phospholipids, rapid shedding of cells
resulting from epidermal growth factor, normal mucosal
blood flow, prostaglandin-stimulated bicarbonate, mucus
production, and inhibited acid secretion.
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Contributors to mucosal inflammation and ulceration include
endogenous factors, such as gastric acidity (approximates
adult values by age 3-4 y), acid-dependent pepsin and
mucosal ischemia, and exogenous factors, such as drugs
(eg, NSAIDs, aspirin, corticosteroids), alcohol, cigarette
smoking, corrosive chemicals (eg, lye), and emotional stress.
In patients with traumatic injuries, burns, sepsis, respiratory
failure, or other critical systemic illnesses, many factors can
contribute to erosions and ulcers, including mucosal
ischemia, increased gastric acid and pepsin production,
higher levels of endogenous catecholamines and steroids,
and decreased prostaglandins and mucus production.
Important mediators of mucosal inflammation and resultant
ulceration include oxygen free radicals, lymphokines,
platelets activating factors, tumor necrosis factor,
leukotrienes, and monokines.
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The gram-negative spirochete, H pylori, was first linked to
gastritis in 1983. Since then, further study of H pylori has
revealed that it is a major part of the triad, which includes
acid and pepsin, that contributes to primary peptic ulcer
disease. The unique microbiologic characteristics of this
organism, such as urease production, allows it alkalinize its
microenvironment and survive for years in the hostile acidic
environment of the stomach, where it causes mucosal
inflammation and, in some individuals, worsens the severity
of peptic ulcer disease.
FREQUENCY
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Peptic ulcer disease has changed profoundly over the last
few decades in Western countries in both children and
adults. The proportion of H pylori –positive ulcers has
declined, and the prevalence of H pylori –negative gastric
ulcers and duodenal ulcers has grown. In a recent
retrospective study from China, 6.9% of children undergoing
esophagogastroduodenoscopy had an ulcer; almost half of
these cases (46.5%) had no associated H pylori infection.1
These data are different from that of other studies, in which
only 20-27% of childhood peptic ulcers were not associated
with either NSAID use or H pylori infection.
The prevalence of H pylori infection in developing countries
is as high as 50-100%. The prevalence of peptic ulcer
disease is increasing in developing countries. In a
retrospective review of 112 Taiwanese children undergoing
upper GI endoscopy for upper GI bleeding, gastric ulcer was
confirmed in 10% and duodenal ulcer was confirmed in 15%.
CLINICAL
HISTORY
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In children in whom peptic ulcer disease (PUD) is suspected,
include the following in the history:
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Review of past illnesses and chronic medical conditions
Family history of ulcer disease, including known H pylori infection, or
conditions affecting the GI tract (eg, Crohn disease)
Character, location, frequency, duration, severity, and exacerbating
(especially meals in children) and alleviating factors of abdominal pain
Vomiting and description of gastric material
Bowel habits and description of stool (eg, profuse diarrhea seen in
Zollinger-Ellison syndrome [ZES])
Prescribed and over-the-counter (OTC) medications, especially
nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids
Prior diagnostic testing and specific GI therapies
Appetite, diet, and weight changes
Family and social stressors
Alcohol ingestion and smoking habits
Crohn's disease, also called regional enteritis, is a chronic inflammation of the
intestines which is usually confined to the terminal portion of the small intestine,
the ileum. Ulcerative colitis is a similar inflammation of the colon, or large
intestine. These and other IBDs (inflammatory bowel disease) have been linked
with an increased risk of colorectal cancer.
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Abdominal pain is the most common symptom of childhood
peptic ulcer disease.
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The pain is usually dull and vague. The pain is most likely to be dull and
aching rather than sharp and burning, as adults describe. Food intake
often causes the pain to worsen; this is the opposite of the adult
pattern.
The pain may be poorly localized or localized to the periumbilical or
epigastric areas.
In preschool-aged children, the pain is typically periumbilical and
worsens after eating.
Younger children may not localize pain and present with anorexia and
irritability.
After the age of 6 years, the child's description of pain may be similar to
the description by adults. The classic pain of peptic ulcer disease (ie,
pain that awakens the child, worsens with food, and is relieved by
fasting) is described infrequently, but it helps in distinguishing GI
pathology from psychogenic pathology when present.
Frequent exacerbations and remissions of pain extend over weeks to
months.
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Vomiting in infants and toddlers may be associated with slow
growth. Recurrent vomiting is also noted in preschool-aged
and school-aged children.
GI tract bleeding (eg, melena, hematochezia, hematemesis)
may be another presentation in children.
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In infants and particularly neonates, serious underlying illness
and stress ulceration most commonly manifest as acute
perforation or hemorrhage.
GI bleeding may lead to iron-deficiency anemia (IDA), and patients
may present with vague complaints of fatigue, headache,
dyspnea, or malaise.
As many as 25% of children with duodenal ulcer have silent
presentation with painless upper GI bleeding or iron deficiency
anemia.
For children with ulcer perforation, the symptoms are
consistent with peritonitis and abrupt in onset.
PHYSICAL
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Children with peptic ulcer disease leading to complications
(eg, severe blood loss in the GI tract, perforation,
obstruction) can appear acutely ill and have evidence of
hemodynamic instability or signs of an acute abdomen.
Children with long-standing peptic ulcer disease from H
pylori may become profoundly anemic from undetected
chronic bleeding and have no complaints.
H pylori
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Include the following in the physical examination:
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Observation of the general appearance of the child
Evaluation of vital signs
Assessment of perfusion with attention to mental status, heart
rate, pulses, and capillary refill
Assessment of hydration status with attention to moisture of the
mucous membranes and skin turgor
Observation of any pallor of the skin and conjunctivae
Thorough chest examination
Careful inspection, auscultation, and palpation of the abdomen,
with notation of any liver or spleen enlargement
Rectal examination and stool guaiac testing
Pelvic examination in sexually active female patients with pain
Examination of the testicles and inguinal area in male patients
Hemorrhage accompanies peptic ulcer disease in 15-20% of
patients.
Acute abdomen resulting from perforation of the GI tract
occurs in 5% of children with peptic ulcer disease.
CAUSES
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Primary peptic ulcer disease
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Primary peptic ulcer disease can be divided into the following:
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H pylori– associated disease
H pylori– negative/idiopathic disease
Hypersecretory states - ZES, gastrin (G)-cell hyperplasia/hyperfunction
systemic mastocytosis, cystic fibrosis, short bowel syndrome, and
hyperparathyroidism.
Genetic factors may be important, as indicated by the observation
that as many as 50% of children with peptic ulcer disease have a
first-degree or second-degree relative with peptic ulcer disease. In
addition, a concordance rate that is 3 times higher in monozygotic
than in dizygotic twins has been described, and children with
blood group O have an increased incidence of peptic ulcer
disease.
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Emotional stress has been described as a factor that predisposes
children to peptic ulcer disease.
Alcohol has been documented to produce inflammation, erosions,
and hemorrhage in the gastric mucosa in animal and adult
human studies. Caffeine intake also predisposes children to
peptic ulcer disease.
Compared with people who do not smoke cigarettes, those who
do are twice as likely to develop peptic ulcer disease. Smoking
may lead to ulceration, slow healing, and an increased risk of
recurrent disease.
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Secondary peptic ulcer disease
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Corticosteroids, NSAIDs, and aspirin use predispose children to
ulceration. These drugs disrupt the mucosal permeability barrier,
rendering the mucosa vulnerable to injury. As many as 30% of
adults taking NSAIDS have GI adverse effects. Although the
prevalence of NSAID gastropathy in children is unknown, it seems
to be increasing, especially in children with chronic arthritis
treated with NSAIDS. Recent case reports have demonstrated
gastric ulceration from low-dose ibuprofen in children, even after
1 or 2 doses
Secondary peptic ulcer disease (PUD)
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Serious systemic illness, sepsis, hypotension,
respiratory failure, and multiple traumatic injuries
increase the risk for secondary (stress) ulceration.
 Ulcers
associated with a brain tumor or injury, or Curling
ulcers, are characterized as single, deep, and prone to
perforation. They are associated with high gastric acid output
and are located in the duodenum or stomach.
 Extensive burns are also associated with ulcers, namely
Curling ulcers.
 Stress ulceration and upper-GI hemorrhage are complications
that are increasingly encountered in critically ill children in the
intensive care setting. Severe illness and a decreased gastric
pH are related to an increased risk of gastric ulceration and
hemorrhage. Neutralization of gastric acid inactivates
proteolytic pepsin, which is responsible for gastric mucosal
injury. Therefore, gastric pH of critically ill children should be
maintained at more than 6 to prevent injury.
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Other causes of secondary ulcers include the following:
Allergic gastritis and eosinophilic gastritis
 Cytomegalovirus
 Graft versus host disease
 Uremic gastropathy
 Henoch-Schönlein gastritis
 Corrosive gastropathy
 Celiac disease
 Hepatic cirrhosis
 Bile gastropathy
 Autoimmune disease
 Exercise
 Crohn disease
 Other granulomatous gastritides (eg, sarcoidosis, histiocytosis X,
tuberculosis)
 Phlegmonous gastritis and emphysematous gastritis
 Other infections, including Helicobacter heilmanni, herpes simplex,
influenza,
syphilis,
Candida
albicans
,
histoplasmosis,
mucormycosis, and anisakiasis
 Radiation gastropathy
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Cytomegalovirus
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ZES is a rare disorder that can cause gastric or duodenal
ulcers (usually multiple) from excessive acid secretion.
Consider ZES if a patient has severe peptic ulceration, kidney
stones, watery diarrhea or malabsorption. ZES can also be
associated with multiple endocrine neoplasias type I, which
occurs earlier than isolated ZES. In addition to the typical
pancreatic gastrinomas, ZES has been reported in children
with solitary extrapancreatic gastrinomas in the stomach,
liver, and kidney. Compared with adult disease, malignant
gastrinomas in children are slow growing. Patients with ZES
usually have fasting serum gastrin levels of more than 200
pg/mL and basal gastric acid hypersecretion at more than 15
mEq/h. Protein pump inhibitor therapy should be
discontinued at least 2 weeks before the gastrin level is
measured.
DIFFERENTIAL DIAGNOSES
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Appendicitis
Gastroesophageal
Reflux
Cholecystitis
Intussusception
Cholelithiasis
Pancreatitis and
Pancreatic Pseudocyst
Crohn Disease
Pneumonia
Esophagitis
Pyelonephritis
Gastroenteritis
Zollinger-Ellison
Syndrome
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Other Problems to Be
Considered
Autoimmune gastritis
 Chronic recurrent
abdominal pain
 Eosinophilic gastritis
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LABORATORY STUDIES
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A minimum of laboratory studies may be indicated in
children with mild peptic ulcer disease (PUD) symptoms
and normal examination findings. The following
laboratory data may be needed in children who are in
unstable condition, in those who have severe or chronic
or recurrent symptoms, or in those with serious
complications of peptic ulcer disease.
Hemoglobin and hematocrit tests: These may be
indicated to diagnose anemia in the setting of chronic
blood loss from the GI tract, to determine the severity of
anemia in the setting of acute or massive GI bleeding,
and to guide and monitor transfusion or iron therapy.
PROCEDURES
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Esophagogastroduodenoscopy
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Esophagogastroduodenoscopy (EGD) is the procedure of choice
for detecting peptic ulcer disease in the pediatric population.
EGD allows for direct visualization of the mucosa; for localization
of the source of bleeding; and for the diagnosis of H pylori
infection by analyzing biopsy specimens, performing cultures or
detecting urease activity.
Therapeutic endoscopy for acute bleeding (coagulation of a
bleeding ulcer with a heater probe or injection with
vasoconstricting agents) is another important indication for EGD.
More than 90% of duodenal ulcers are found in the duodenal
bulb. An erosion is small (<3 mm) and superficial defect in the
mucosa.
Consider nasogastric (NG) lavage in a child who is ill and in whom
upper-GI hemorrhage is suspected because of hematemesis or
melena.
the gross appearance of an active ulcer is a round or
oval, punched-out lesion with a smooth, white base and
surrounding mucosa that is red and edematous.
Most gastric ulcers are located in the lesser
curvature of the stomach.
MEDICAL CARE
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In children with peptic ulcer disease (PUD) who appear to be
well, in whom examination findings are normal and
symptoms are mild, evaluation may be conducted on an
outpatient basis.
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The eradication of H pylori relies on a multidrug regimen.
Triple therapy is considered to be the standard treatment for
children, including a proton pump inhibitor combined with 2
antibiotics. This regimen has been shown to be very effective
in eradicating H pylori from the stomach. The current
recommendation
is
treatment
with
amoxicillin,
clarithromycin, and a proton pump inhibitor for 2 weeks.
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Non-H pylori peptic ulcer disease is effectively treated with
acid suppression; however, prospective studies are lacking.
Complete healing and resolution of symptoms requires
appropriate therapy for underlying etiology, as in Crohn
disease.
Proton pump inhibitors are increasingly used in the pediatric
population, especially in children with gastroesophageal
reflux disease (GERD), than before. Proton pump inhibitors
provide consistent gastric pH control, and patients do not
develop tachyphylaxis with repeated dosing.
A recent study in hospitalized adult patients revealed no
significant difference among various proton pump inhibitors
given through different routes (intravenous [IV] vs oral [PO])
on raising intragastric pH levels above 6 for 72 hours after
successful endoscopic hemostasis in patients with a
bleeding peptic ulcer.8 In addition standard-dose proton
pump inhibitor infusion was as effective as a high-dose
regimen in reducing the risk of recurrent bleeding.
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The risk of adverse effects appear to be minimal with longterm administration. The number of gastrin-secreting cells (G
cells) increases, as does the ratio of G cells to D cells. The
clinical significance of this effect is unknown. Long-term
studies have demonstrated hypergastrinemia and
enterochromaffinlike cell hyperplasia in children receiving
continuous proton pump inhibitor therapy, but this has not
affected histologic findings or caused an increase risk for
carcinoid formation.
Small gastric polyps may develop in some patients during
proton pump inhibitor maintenance therapy. These polyps
usually develop in the gastric corpus and are hyperplastic or
benign fundic gland cysts.
Rebound acid hypersecretion arises from the trophic effects
of the proton pump inhibitor–induced hypergastrinemia; 44%
of previously asymptomatic subjects experienced clinically
significant heartburn, acid reflux, or dyspepsia after
discontinuing a 2-month course of esomeprazole at 40 mg/d
compared with 15% after placebo.
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Sucralfate is an aluminum salt of sulfated sucrose, which, in
the presence of acid pH, forms a complex, pastelike
substance that adheres to the damaged mucosal area. It
forms a protective coating that acts as a barrier between the
lining and gastric acid, pepsin, and bile salts.
Misoprostol is a synthetic prostaglandin E1 analog with
gastric antisecretory and cytoprotective properties. It is
effective in adults for the prophylaxis and treatment of
nonsteroidal anti-inflammatory drug (NSAID)-induced
gastropathy. Studies on the benefits of misoprostol
administration in children are limited.
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Optimal management of severe or refractory peptic ulcer
disease requires a multidisciplinary team approach, using
primary care providers, gastroenterologists, and general
surgeons. Medical management has become the
cornerstone of therapy. Identification and eradication of
recurrent H pylori infection can heal ulceration and also
prevent recurrence. Severe, intractable, or recurrent peptic
ulcer disease with associated complications mandates a
careful evaluation to determine potential etiologies like
gastrinomas or Crohn disease
MEDICATION
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Histamine H2-receptor antagonists
Ranitidine (Zantac)
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Neonates: 2-4 mg/kg/d PO divided q8-12h or 2 mg/kg/d IV
divided q6-8h
Infants and children: 6-9 mg/kg/d PO divided q8-12h or 2-4
mg/kg/d IV divided q6-8h
Continuous infusion: Administer daily IV dose over 24 h
Proton pump inhibitors
Omeprazole (Prilosec, Zegerid)
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0.6-0.7 mg/kg/d PO initially, may increase to 0.6-0.7
mg/kg/dose PO bid; reported effective dose range 0.7-3.3
mg/kg/d
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Antacids
Aluminum and magnesium hydroxide (Mylanta, Maalox)
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hs
50 mg/kg/d PO divided bid; not to exceed 2-3 g/d
Clarithromycin (Biaxin)
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and
Antibiotics
Amoxicillin (Amoxil, Trimox)
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5-15
mL
PO
q3-6h
or
q1-3h
pc
Alternative: 1-2 chewable tab PO q1-3h pc and hs
7.5 mg/kg PO bid for 2 wk (with omeprazole and metronidazole or
with omeprazole only) or for 10 d (with amoxicillin and
omeprazole)
GI agents
Sucralfate (Carafate)
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Not established; 40-80 mg/kg/d PO divided q6h have been used