++
Patients with gastritis or gastropathies may or may not have
symptoms, and when symptoms occur, they are seldom specific. The
classically reported symptoms of peptic ulcer disease include gnawing
or burning epigastric pain that occurs 2 to 3 hours after meals
and is relieved by antacids. This presentation is uncommon in children.
True epigastric pain is relatively uncommon in children and always
requires investigation, as does upper gastrointestinal (GI) bleeding
with or without pain. A temporal relationship of pain with meals
occurs in only about half of children with peptic ulcer disease.15-17 Peptic
disorders may also present with symptoms of nausea, vomiting, and
weight loss. Symptoms of H pylori ulcer disease,
non–H pylori ulcer disease, and the various
gastritides and gastropathies overlap with those of hepatobiliary
disease, pancreatitis, and with functional disorders such as nonulcer
dyspepsia or functional heartburn. A detailed approach to history
taking and differential diagnosis in childhood abdominal pain is
described in Chapter 384. In children presenting
with abdominal pain, blood loss, anemia, or upper GI lesions at
endoscopy, it is particularly important to actively solicit a history
of use of over-the-counter NSAIDs, as parents and children often
fail to mention nonprescription drugs in the medication history. The
most common causes of abdominal pain in children are constipation
and irritable bowel syndrome, and although these conditions usually
present with nonepigastric pain, difficulties may arise when the
child is unclear about the nature and location of the pain—which
is not infrequently the case.7,18
++
On physical examination, epigastric tenderness is an unreliable
sign of peptic disease because other disorders may cause similar
findings. Referred pain to the back may suggest a perforated ulcer.
GI bleeding may occur with longstanding antecedent epigastric pain
or other symptoms, but painless bleeding may be the only manifestation
of ulcer disease. In fact, of children with endoscopically proven
duodenal ulcers, up to 25% of children have a “silent” presentation;
about 25% present with bleeding and antecedent pain, and
the rest present only with abdominal pain or recurrent vomiting.19,20 Iron
deficiency anemia may be a consequence of H pylori gastritis,
even in the absence of pain or ulcer disease.21 Peripheral
edema from hypoalbuminemia suggests a diagnosis of Menetriere disease.
Rarely, a succession splash may suggest a gastric outlet obstruction.
++
In infants and toddlers, and children who are neurologically
impaired, symptoms are even less specific and may include only unexplained
crying, arching, or grimacing. These symptoms are nonspecific and
may be due to a variety of causes, which include constipation, “infant
colic,”22 sensitivity to cow or soy milk
protein, infection, exposure to tobacco smoke, social neglect, and
gastroesophageal reflux disease.23,24
++
A positive family history of peptic ulcer disease may support
a clinical suspicion of peptic disease. However many individuals
have been told they have “an ulcer” or “gastritis” on
the basis of a clinical impression, or a questionable barium study,
without an accurate diagnosis having been made. More often than
not, this makes the family history of questionable relevance, unless it
can be verified by an endoscopy report.
+++
Diagnostic Evaluation
++
The diagnostic approach to peptic disorders depends upon the
diagnostic presentation. Those patients with upper gastrointestinal
(GI) bleeding are best evaluated as described in Chapter 387. Upper endoscopy provides a definitive diagnosis and may
allow therapeutic interventions in the case of an ulcer. In most
children, the symptoms of peptic disease are less specific so a
decision regarding the need for further evaluation depends upon
the frequency and intensity of the symptoms, as well as how disruptive
the symptoms are to the child’s normal daily activities.
Patients with nonspecific symptoms with suspected peptic disease
are often treated empirically with antacids, histamine-2-antagonists
(H2RAs) blockers, or proton pump inhibitors (PPIs). Those who have
significant symptom relief or repeated response to these therapies
most likely have some form of acid peptic disease, but a response
to empiric therapy does not provide a specific diagnosis or guide
treatment. For symptoms that are chronic or relapsing, an upper
GI endoscopy with biopsy is required to help differentiate between
the varying causes of symptoms, preferably while off acid-suppressing
therapy for at least 1 to 2 weeks.2,3,4,5
++
Specific diagnostic testing is available for H pylori, but
this testing does not distinguish between H pylori infection
and H pylori disease (see discussion below). Initiation
of treatment based upon these tests alone is not recommended.25-28 Upper
GI contrast studies (“upper GI series” or “barium
study”) have no role in the diagnosis of gastritis or uncomplicated
peptic ulcer disease because findings are frequently falsely positive
or falsely negative for gastric mucosal disorders, including ulcers.20,29,30 Findings,
such as “poor filling of the duodenal cap,” “irritability
of the duodenum,” or “duodenitis” are
nonspecific. Rarely, radiology identifies an ulcer crater, but because
radiography cannot distinguish between causes of ulceration, endoscopy
with biopsies is still necessary to determine the underlying cause
of ulceration and whether the findings are relevant to the child’s
symptoms. However, upper GI contrast studies are helpful with some
symptom presentations to exclude malrotation, or other anatomic
abnormalities such as ulcer-related complications including antral
or pyloric outlet narrowing, or perforation.
++
Endoscopy and biopsy allow categorization of entities as erosive
and hemorrhagic or nonerosive. This helps to narrow the diagnostic
possibilities as shown in Table 409-1, but
because most gastritis and ulcer disease are part of a continuum
of response to injury, the endoscopic findings of any mucosal abnormality
including erosions or ulcer (Fig. 409-2 and eFig. 409.1) do not delineate a cause of
the lesion. For example, although Crohn disease and cytomegalovirus
gastritis are most often nonerosive, they often progress to erosions
and ulcers. H pylori gastritis is classified as
nonerosive, because it most often presents with normal or nodular
mucosa, with abnormalities seen only on histologic examination,
but it can cause erosions or ulcers in the stomach and duodenum.
++
++
++
++
Following demonstration of an ulcer diagnostic classification
as either primary peptic ulcer disease or secondary disease is useful
(Table 409-2).25-28 The
most common cause of primary ulcers is H pylori.
Although categorization is based on etiology, primary peptic
ulcers are usually chronic, with fibrinopurulent debris overlying
active inflammatory infiltrate, granulation tissue, and fibrosis.31 In
contrast, secondary peptic ulcers are usually acute
in onset, often induced by physiologic stress or drug ingestion,
and usually are not fibrotic. Primary peptic ulcers are more often
duodenal, whereas secondary ulcers are more often gastric. Secondary
ulcers are those occurring in the presence of systemic underlying
disease, whereas in primary ulcer disease this is usually not present.
Primary peptic disease is uncommon below the age of 8 years or so,
whether H pylori related or not.19,20,25,26,28 Secondary
ulcer disease occurs at all ages, depending on the cause of the
underlying gastritis.
++
++
Delineation of a specific or most likely diagnosis requires a
careful review of the biopsy in the context of the clinical scenario.5 Specific diagnostic
entities are discussed below. Biopsy interpretation is often only
descriptive, and semiquantitative. The types of cell present and
their distribution in the mucosa is described. “Acute” or “active” refers
to the presence of neutrophils, “chronic” refers
to the presence of round cells (lymphocytes, monocytes, plasma cells),
and “chronic active” refers to a combination of
a chronic process with some neutrophils present. There are no precise
definitions for chronic gastric inflammation because the “normal” number
of mononuclear “allowable” is unknown32-34 Although
adult “normal” or asymptomatic volunteers sometimes
undergo endoscopy and biopsy as a baseline for studies, their histology
even in “health” may reflect many variables, such
as normal aging, smoking, intake of alcohol, NSAIDs, and so forth.
These findings cannot be extrapolated to children, who should have “virgin” mucosa,
unaffected by aging or toxins, unless a recent infection, including a systemic viral infection
has occurred. In addition to the types of cells and lymphoid collections,
descriptive terminology also includes the extent or depth of inflammation
in the mucosa (superficial, deep, or pan-mucosal) and distribution
(diffuse or focal). These terms can be combined to provide an overall
description, for instance, “chronic active, pan-mucosal.”19
+++
Differential Diagnosis
+++
Helicobacter
Pylori–Associated Gastritis and Ulcer
++
Gastric infection with H pylori is one of the
most common causes of gastritis and peptic ulcer disease. H
pylori organisms are spiral-shaped gram-negative, urease-producing
bacteria that are highly motile because of multiple unipolar flagella. H
pylori colonizes the mucus layer of the stomach, adjacent
to the gastric mucosa. The prevalence of gastric infection with H
pylori varies between countries and socioeconomic groups,
but even where it is common, children are considerably less susceptible
to peptic ulcers and other sequelae than adults. Improved sanitation
and socioeconomic status decrease childhood H pylori acquisition
rates.35 In most individuals, it is “silent” or
asymptomatic and most often unassociated with complications. However,
antral-predominant gastritis causes high-output gastric acid secretion,8,9,36-38 and
it has a lifetime incidence of 10% to 15% of development
of duodenal ulcer disease.39,40
++
In its acute phase, H pylori causes an acute,
active (neutrophilic) gastritis, antral-predominant. The acute infection
is accompanied by symptoms and increased acid hypersecretion for
a week or so, then by hypochlorhydria,41,42 lasting
for 6 weeks or so, after which serum gastrin levels and acid secretion
are elevated, or occasionally normal. This fluctuation probably
has to do with the areas of stomach infected, but the commonest residuum,
at least when ulcer disease is present, is acid hypersecretion.38 If
the organism is not eradicated, in most cases, the gastritis becomes
chronic and active. Virtually all individuals infected with H
pylori have some gastritis, but there are considerable
individual and geographic variations in intensity and distribution
of inflammation and in the disease associations. Two typical distribution
patterns of infection in the stomach are observed with different
pathophysiology. The first is an antral-predominant gastritis associated
with increased gastric acid production. Individuals with this pattern
of distribution are prone to peptic ulcer disease (PUD). This has
been postulated to be due to the organism secreting ammonia resulting
in a local increase in mucosal pH which in turn increases gastrin
secretion. However, the mechanisms by which H pylori–associated
gastritis causes ulceration in the duodenum remain unclear.43 The
second distribution pattern of H pylori infection
is a pan-predominant gastritis or corpus-predominant gastritis with
decreased gastric acid production which are more prone to developing
gastric atrophy (intestinal metaplasia and possibly gastric adenocarcinoma).
The most prevalent pattern of gastritis in children19 in
the Western world is an antral-predominant gastritis, with little
or no involvement of the body (corpus) of the stomach.
++
Primary gastritis per se (ie, without ulcer disease), even though
otherwise silent, causes iron-deficiency anemia in some children.21H
pylori is a cofactor in the development of the very rare
gastric B-cell lymphoma arising from mucosa-associated lymphoid
tissue, or MALT, that is rare in childhood but has been described
in children aged 11 to 16 years, with subsequent cure after H
pylori eradication in some.6
++
As a general principle, diagnostic tests for H pylori should
be employed judiciously and be reserved for those children who are
most likely to derive measurable benefit such as those who reasonably
may be suspected to have peptic ulcer disease. H pylori infection
in developed countries is low, and, in the absence of peptic ulceration, H
pylori is only rarely a cause of symptoms.44 A
positive urea breath test merely indicates that H pylori infection
is present, not that it is the cause of symptoms; it is neither
diagnostic of specific gastroduodenal pathology nor rules out other
diagnoses. Abdominal pain in children is more commonly due to causes
other than H pylori; therefore, testing for H
pylori in all children presenting with abdominal pain is
not indicated. Expert consensus groups have recommended that in
children presenting with abdominal pain, the goal of diagnostic
testing should be to determine the cause of the pain, not the presence
of H pylori.25-28
++
In contrast, in adults, guidelines recommend the use of H
pylori testing (urea breath tests or stool antigen tests)
of adults with persistent dyspepsia, followed by treatment of those
with positive tests.45
++
Antibody tests utilizing whole blood, serum, or saliva are not
recommended in children for clinical use. Antibody tests are of
low sensitivity and specificity—they may remain positive
for years after eradication or resolution of infection; therefore,
a positive test does not necessarily mean that active infection
is present at the time of testing. The urea breath test (UBT) is
sensitive and specific for the presence of active infection. Monoclonal
stool antigen tests are less accurate for the presence of H
pylori,46,47 and there is insufficient
evidence to recommend fecal antigen testing in children.25-28
++
Endoscopy with biopsies provides the most accurate approach for
definitive diagnosis of upper gastrointestinal mucosal diseases,
including H pylori–associated disorders.
Although H pylori gastritis may be present at endoscopy,
it may not be the cause of presenting symptoms if ulcer disease
is not present.25-28 Marked nodularity (see Fig. 409-3 and eFig. 409.2) is present in the antrum of
patients in approximately 50% of children with H
pylori gastritis without peptic ulcer disease, and in virtually
all those with H pylori gastritis with peptic ulcer
disease.19 Peptic ulcers that are H pylori related
look the same endoscopically as H pylori–negative
ulcers—the presence of H pylori gastritis
makes the distinction.
++
++
++
If active H pylori infection is present in a
symptomatic patient, it is considered prudent to eradicate the organism.
These recommendations are largely based upon the belief that treatment
will potentially decrease the risk of gastric cancer. Eradication
of H pylori is best acheived with a combination
of 3 drugs.25-28 Examples of such regimens are
a PPI approved for use in children, plus amoxicillin plus clarithromycin;
or, PPI plus amoxicillin plus metronidazole; or PPI plus clarithromycin
plus metronidazole. The medications are all given as twice-daily
doses for 2 weeks; compliance is key to success of eradication. Elimination
of H pylori is followed closely by the disappearance
of neutrophils, which may be completely absent within 1 week of
treatment. The chronic inflammation and the lymphoid hyperplasia
subside more slowly, often taking longer than 1 year.19,48-50 Confirmation
of eradication of H pylori with a UBT is recommended.25-28
++
Eradication of H pylori infection results in
ulcer cure, with very low rates of ulcer recurrence. Potential sequelae
of persistent H pylori infection include atrophic
gastritis and intestinal metaplasia with a risk for gastric cancer
(see atrophic gastrititis below).
+++
Other Infectious
Gastritides
+++
Helicobacter
Heilmanii
++
This organism, previously Gastrospirillum hominis,
is probably transmitted from cats and dogs51,52 and
may cause chronic active gastritis similar to that of H
pylori, but with less severe inflammation, which is focal
and usually restricted to the antrum. A definite association between H
heilmanii infection and ulcer disease has not been established.
++
Acute gastric anisakiasis occurs frequently in Japan and in areas
of high consumption of raw fish. Gastric symptoms may occur within
3 hours of ingestion and in sensitized people systemic allergic
symptoms may arise within 5 hours. Peripheral leukocytosis and eosinophilia may
also occur. Endoscopy shows one or more worms protruding into the
lumen a couple of millimeters off the gastric mucosa, surrounded by
a ring of intense erythema, mucosal swelling, and sometimes gastric
erosions. The worms can be in the antrum or body but tend to favor
the greater curvature of the stomach. Early endoscopy is diagnostic
and therapeutic, allowing for removal of worms and relief of symptoms.
+++
Other Gastric
Infections
++
Several gastric infections have been described in immune-suppressed,
sick, or malnourished individuals, including newborns with some
infections (see Chapter 391). These include
cytomegalovirus (CMV)53, herpes simplex, candidiasis,
histoplasmosis, mucormycosis Mycoplasma pneumoniae, Mycobacterium
tuberculosis, syphilis, Epstein–Barr virus, herpes
zoster varicella virus, ascaris lumbricoides, strongyloides
stercoralis. Influenza A is a rare cause of bleeding from
hemorrhagic gastropathy in children and is sometimes fatal.54 CMV
infection tends to occur in the gastric fundus and body, and may
cause wall thickening, ulceration, hemorrhage, and perforation.55 Histologic
findings include acute and chronic inflammation with edema, necrosis,
and cytomegalic inclusion bodies in epithelial and endothelial cells,
as well as in ulcer bases and mucosa adjacent to ulcers.
+++
Helicobacter
Pylori–Negative Gastritis and Ulcer
++
The exact prevalence of H pylori–negative duodenal
and gastric ulceration is unclear, ranging from 1.7% to
48% in both the adult and the pediatric population.6 Some
adult studies report a prevalence of H pylori–negative
duodenal and gastric ulceration as low as 1.7% and 3.2%,
respectively,56 whereas others report H
pylori–negative duodenal ulcer disease rates of
8% to 12%,57,58 up to 48%.59 The
few data in children indicate a prevalence of up to 29%.58,60,61 In
children with H pylori–negative duodenal
ulcer disease, the gastric antrum is normal at endoscopy and histologically;
this is in contrast to the findings in H pylori–associated
ulcer disease. That there are widely differing prevalences of H
pylori–negative ulcer disease likely reflects
different degrees of thoroughness of exclusion of H pylori infection,
as well as truly changing prevalences of H pylori infection
within communities as eradication treatments are used. H
pylori–negative ulcer disease can be diagnosed
only when H pylori infection has been reliably
excluded (use of more than one test) and in the absence of recent
antibiotic or bismuth ingestion (partial treatment of H
pylori). NSAID ingestion and other conditions that cause
ulcer disease, such as Crohn disease, Zollinger–Ellison
syndrome, and G-cell hyperplasia, also must be excluded.
+++
Atrophic Gastritis
and Intestinal Metaplasia
++
Atrophic gastritis, also known as “gastric atrophy,” describes
a loss of normal gland components or the presence of intestinal
metaplasia. It is considered to be a preneoplastic lesion when a certain
type of intestinal metaplasia develops in the atrophic mucosa.62-64 Atrophic
gastritis of the stomach is a patchy lesion and may be missed by
sampling error if tissue from multiple sites is not obtained. There
is relatively little information on atrophic gastritis in children. When
it does occur, it generally does so in the presence of H
pylori, after the age of 10 years, with intestinal metaplasia
very infrequently present.65,66-69 As the degree
of atrophy progresses, the presence of active H pylori infection
decreases, owing to the loss of H pylori–friendly,
acid-secreting, superficial gastric mucosa, and newly present intestinal
metaplasia that does not harbor H pylori. The supervention
of hypochlorhydria is also somewhat hostile to H pylori colonization,
because in the absence of acid, other organisms can proliferate
and offer competition for H pylori. The acid–H
pylori relationship and the mechanisms of development of
atrophy have been well described elsewhere.36 Although H
pylori infection is far and away the most important cause
of atrophic gastritis worldwide, atrophy may result from any severe,
chronic mucosal injury to the gastric mucosa in disorders such as
in severe chronic varioliform gastritis and in autoimmune disease
(scleroderma) with gastrointestinal tract involvement, including
in children.1
++
Ménétrièr disease is a rare condition
characterized by giant gastric folds, excess mucus secretion, decreased
acid secretion, and hypoproteinemia due to the selective loss of
serum proteins across the gastric mucosa. Although this condition
is reported from the neonatal period onwards, the mean age of onset in
children is 4.7 years.70 In children, it may follow
a viral prodrome. Presentation includes epigastric pain, anorexia,
vomiting, edema, hypoproteinemia, and raised IgE levels in some.71 Fecal
alpha-1-antitrypsin levels are often elevated as in other protein-losing
enteropathies. In children, it is generally a benign self-resolving
disorder that may be associated with acute cytomegalovirus (CMV)
infection.71,72 In adults, Ménétrièr
disease is a more severe disease that is an acquired premalignant
disorder. It may even present with malignancy. The diagnosis of
Ménétrièr disease is made by endoscopy
and biopsy. The differential diagnosis includes consideration of
other disorders associated with large gastric folds including lymphoma,
infections such as H pylori, CMV and anisakiasis,
granulomatous gastritides, eosinophilic and allergic gastritis,
and other rare disorders such as plasmacytoma and systemic lupus
erythematosus. Some “thick fold” diseases may require
full-thickness gastric biopsy, but Menetrier disease does not. Dramatic
resolution of many manifestations in adults has been reported with
the use of anti-EGFR antibody. Ganciclovir may be beneficial in
children.73
+++
Nonsteroidal
Anti-Inflammatory Drugs (NSAIDs), Aspirin, and Other Drugs
++
There are few data on the frequency of adverse gastrointestinal
(GI) effects of NSAIDs in children, but they do occur.74,75,76,77-81 Though
the conventional wisdom is that short-term use of NSAIDs for fever
control is safe, a recent case series suggests otherwise.81 As
in adults, erosions and ulcers due to NSAIDs may be single or multiple;
the gastric antrum tends to be involved more than the body, but
any or all regions of the stomach may be involved. In young children,
ulceration of the incisura presenting with upper GI bleeding is
a typical NSAID lesion, and bleeding may occur after just 1 or 2
doses of drug, or with more chronic use. NSAIDs can result in mucosal
damage, ranging from histologic changes alone to frank ulceration;
patients may be asymptomatic or suffer life-threatening ulcer bleeding
or perforation. Many patients have gastric erosions when starting
on NSAIDs, but often are asymptomatic and the erosions often heal
spontaneously82—the phenomenon of “gastric
adaptation.” Although enteric-coated (“buffered”)
aspirin may cause fewer symptoms, enteric-coating of aspirin does
not prevent complications.83
++
Risk factors for gastrointestinal complications of NSAIDs include
a history of ulcer (complicated or uncomplicated), drug dose, comcomitant
use of aspirin and another NSAID, use of a corticosteroid, use of
an anticoagulant, and, possibly, H pylori infection.84 Current
evidence suggests that eradication of H pylori is
indicated before instituting high-dose or long-term NSAID therapy.
PPIs and misoprostol are effective in preventing morbidity; the
adverse effects (abdominal cramps, diarrhea) of misoprostol limit its
use. At present there are no data on effectiveness of PPI for prophylaxis
of children receiving NSAIDs.
++
Erosive or hemorrhagic gastropathies have also been described
with valproic acid, dexamethasone, chemotherapeutic agents, alcohol,
potassium chloride, iron, long-term fluoride ingestion, and cysteamine.6
+++
Gastric Acid
Hypersecretory States
++
Zollinger-Ellison syndrome, G-cell hyperplasia, and systemic
mastocytosis are extremely rare in children.85-87 Zollinger-Ellison
syndrome is caused by gastrin-secreting tumors called gastrinomas,
which produce a baseline fasting hypergastrinemia (> 125 pg/mL).4 It
should be noted that plasma gastrin levels well in excess of 100
pg/mL are often seen in patients receiving PPIs.88 Zollinger-Ellison
syndrome may occur in association with multiple endocrine neoplasia
type 1 (MEN1) or as a sporadic form. Hyperparathyroidism, hypercalcemia,
and renal stones are found in patients with Zollinger-Ellison syndrome
and MEN1.4,89,90
++
Systemic mastocytosis is a condition in which mast cells accumulate
in skin, bone, bone marrow, liver, spleen, and GI tract. Mast cell
products such as histamine and cytokines produce a variety of effects,
including gastric hypersecretion, that may be associated with symptoms
of nausea, vomiting, abdominal pain, peptic ulceration, diarrhea,
and malabsorption.91-94 Management with acid suppression
is usually effective.94
++
Other conditions associated with gastric acid hypersecretion
include short bowel syndrome, hyperparathyroidism, and cystic fibrosis.
Peptic ulcer disease is reported in children and adults with short
bowel syndrome, but the exact mechanism remains unclear.95-97 Treatment
with PPIs can be helpful; they may have to be given intravenously
in severe refractory peptic ulcer disease associated with short
bowel syndrome.95 Peptic ulceration, usually duodenal,
can occur in patients with primary hyperparathyroidism as a result
of hypercalcemia-induced gastric acid hypersecretion.98 Cysteamine,
used for treatment of cystinosis is a potent secretagog, causing
hypergastrinemia and gastric acid hypersecretion.6
++
Physiologic stressors such as shock, metabolic acidosis, hypoxemia,
bacterial sepsis, head injury, burns, major surgery, or multiple
organ failure reduce gastric blood flow with subsequent mucosal
ischemia. This impairs the mucosal defensive barrier, increasing
the risk of acid causing mucosal damage, even though hypersecretion
is seen only in cases of sepsis and central nervous system trauma.
Further risk factors for hemorrhage include gastric hypersecretion,
mechanical ventilation, and use of corticosteroids. Stress lesions
usually occur within 24 hours of the onset of critical illness and
result in overt upper GI hemorrhage. The erosions are typically
asymptomatic, multiple, superficial, and tend not to perforate.
++
Most neonatal gastropathies are due to physiologic stress, including
prematurity, hypoxemia, prolonged ventilatory support, sepsis, and
acid–base imbalance. Hemorrhagic gastropathy has been reported
in otherwise healthy full-term infants presenting with severe upper gastrointestinal
hemorrhage,99 and also in one patient as antenatal
hemorrhage,100 most cases of hemorrhagic gastropathy
are reported in sick neonates in the intensive care unit.
+++
Traumatic Gastropathy
++
Forceful retching or vomiting may cause tears either above or
below the gastroesophageal junction (Mallory-Weiss tears)
or may produce typical subepithelial hemorrhages in the fundus and
proximal body of the stomach (prolapse gastropathy101)
from “knuckling” or trapping of the proximal stomach
into the distal esophagus. Although both prolapse gastropathy and
tears tend to resolve quickly, they can result in significant blood
loss. Generally, bleeding ceases spontaneously as vomiting resolves,
but occasionally bleeding from a Mallory-Weiss tear may be severe
enough to warrant endoscopic therapy. By a similar mechanism of
trauma, linear erosions may occur in the herniated gastric mucosa
of patients with a large hiatal hernia, resulting in chronic blood
loss anemia.102 Gastric erosions may also result
from trauma secondary to long-term nasogastric tube placement. Aggressive
continuous suction through nasogastric or gastrostomy tubes, especially
in children who are receiving anticoagulants, can cause severe subepithelial
hemorrhage and bleeding. Ingestion of foreign bodies, gastrostomy
feeding devices, and endoscopic procedures such as diathermy103 are
also common causes of subepithelial hemorrhage, erosion, and ulcer.
+++
Portal Hypertensive
Gastropathy
++
This congestive gastropathy is common in children with both cirrhotic
and noncirrhotic portal hypertension104 but is
not related to the severity of underlying liver disease, the size
of esophageal varices, the presence of hypersplenism, or a previous
history of bleeding and variceal sclerotherapy. Although hemorrhage from
portal hypertensive gastropathy is not usually catastrophic, bleeding
may occur and result in severe blood loss and anemia. In adults,
congestive gastropathy is more frequently associated with large gastroesophageal
varices than with esophageal varices alone, and sclerotherapy of
esophageal varices may exacerbate portal hypertensive gastropathy
and gastric varices. Diagnosis is made by endoscopy alone. Biopsy
is not required and is potentially dangerous.
+++
Gastritis Associated
with Autoimmune Diseases
++
Gastritis with and without atrophy has been seen in children
with autoimmune thyroiditis and nongoitrous juvenile hypothyroidism,
some with achlorhydria and gastric parietal cell antibodies.105 Autoimmune
atrophic gastritis has also been described in 15% of adults
with vitiligo.106 Conversely, hypertrophic gastropathy
has been associated with systemic lupus erythematosus.107 In
children and adults with connective tissue diseases, a mast cell
gastritis and a combination mast cell and eosinophilic gastritis
have been described.108
++
Graft versus host disease (GVHD) is discussed further in Chapter 133. Acute GVHD may involve the stomach
with biopsy findings consisting of crypt epithelial cell apoptosis
and drop-out.109 Chronic GVHD rarely involves the
stomach.
++
The classic adult form of pernicious anemia,
associated with body-predominant atrophic gastritis, occurs rarely
in children. Patients have antibodies against parietal cell components,
including the proton pump, intrinsic factor, and pepsinogen.106 The
typical finding at endoscopy is thin rugae of the gastric body,
sometimes with blood vessels visible through the mucosa. Histologic
examination shows severe atrophic fundic gland gastritis with absence
of parietal cells. It is associated with endocrinopathies such as
autoimmune thyroid disease and diabetes mellitus, vitiligo, selective
IgA deficiency, abnormal cellular immunity, chronic candidiasis,
and collagen vascular disease.110 Adenocarcinoma
of the stomach occurs as a complication. Although gastric adenocarcinoma
is rare in children, it does occur,111 and endoscopic
surveillance of pernicious anemia is indicated. Other causes of
vitamin B12 deficiency are discussed in Chapter 188.
++
GI bleeding in patients with systemic sclerosis and CREST syndrome
has been reported and is most often due to mucosal telangectasia,
although peptic ulcers and erosive gastritis have also been described.112 In
a large group of children with insulin-dependent diabetes mellitus,
7% had upper GI symptoms for which endoscopy was performed113;
half had evidence of erosions and ulcers.
++
In celiac disease (see Chapter 408) gastroscopy
is usually normal, but if biopsies are taken, a lymphocytic gastritis
is often detected as characterized by the intraepithelial location
of the lymphocytic infiltrate.114-116 Rarely, bleeding
from gastric or duodenal ulcers may occur in celiac disease.117
+++
Inflammatory
Bowel Disease and Other Granulomatous Gastridities
++
Crohn disease is the most common cause of granulomatous disease
of the stomach.5 Although gastroduodenal involvement
is relatively common, Crohn disease is rarely isolated to the stomach
and usually also involves more distal intestinal disease.118 If
disease is isolated to the upper GI tract, particularly in younger
children, other conditions such as chronic granulomatous disease
of childhood should be considered and excluded.
++
Chronic granulomatous disease (CGD) is a rare inherited immune
deficiency disorder discussed in Chapter 188.
Gastric involvement typically presents with a narrowed, poorly mobile
antrum on contrast radiography53,119 and a swollen,
pale lusterless anral mucosa. Histologic findings include focal,
chronic active inflammation in the antrum, with granulomata or multinuclear
giant cells. The pathognomonic lipochrome-pigmented histiocytes
may be absent in gastric biopsies but are often evident on biopsies
from the lower gastrointestinal tract.5
++
Other rare granulomatous gastritides include reaction to foreign
bodies, tuberculosis, histoplasmosis, histiocytosis X, sarcoidosis,
Wegener disease, and idiopathic isolated granulomatous gastritis,
a rare condition of a chronic granulomatous reaction limited to
the stomach, and a diagnosis of exclusion.
+++
Other Gastritides
and Gastropathies
++
Allergic and eosinophilic gastroenteropathies are
discussed in detail in Chapter 411. Henoch-Schönlein
purpura (HSP) (see Chapter 472) can involve
the stomach with endoscopic findings that include erythematous or
hemorrhagic mucosa, mucosal edema, with erosions or ulcers.120 Corrosive
injury causes mucosal damage. The ingestion of strong acids and
alkalis usually results in damage to the esophagus but may involve
the stomach. When gastric injury occurs, the prepyloric area is
particularly vulnerable,121,122 probably because
of pylorospasm and pooling of secretions. Endoscopic findings range
from mild friability and erythema to necrosis, ulcers, exudates,
hemorrhage, and gastric outlet obstruction with perforation rarely
occurring. Chronic cicatrization is relatively infrequent and may
take several months to become apparent, hence the need for serial
imaging or evaluation. Iron poisoning, especially with ferrous sulfate,
is common in children in some areas of the world and may cause a
corrosive gastropathy with stricture.123 Therapeutic
administration of oral ferrous sulfate can cause mild endoscopic
abnormalities in the stomach; these are of uncertain clinical significance.124
++
Exercise-induced gastropathy or gastritis occurs
in long-distance runners, usually presenting with blood loss anemia,
with or without upper GI symptoms. Symptoms often occur postexercise
and include abdominal cramps or epigastric pain, nausea, gastroesophageal
reflux, and vomiting.125-127
++
Long-term or high-dose PPI therapy often causes a characteristic
hyperplasia of parietal cells, with a thickened parietal cell zone,
and lingular pseudohypertrophy of individual parietal cells. Endoscopic evidence
of polyps or nodules may occur in children. The changes are benign
and often resolve with cessation of PPI therapy.
++
In acute renal failure, gastropathy may be due
to physiologic stress rather than renal failure. When GI bleeding
occurs in acute renal failure, it is associated with erosions or
ulcers in 71% of cases in adults and with an increased
risk of death and duration of hospital stay; additional factors
that predispose to bleeding are use of corticosteroids and concurrent
disease such as liver cirrhosis.128
++
Duodenogastric reflux causing bile gastropathy was
common in patients who had undergone gastric resection surgery for
peptic ulcer disease. Other than for cancer or rare indications
like hypersecretory syndromes not responsive to acid suppression, these
operations are largely obsolete even in adults these days, making
this disorder uncommon. The mere finding of bile in the stomach
at endoscopy is common and unlikely to be of any significance.
++
Chronic varioliform gastritis is a subacute,
inflammatory gastric mucosal disease characterized by swollen congested
rugae and disseminated mucosal erosions which is exceedingly rare
in childhood.1
+++
Complications
and Treatment
++
Principles of management are given here, with treatments specific
to less common forms of gastritis given under each type of gastritis.
The approach to H pylori is a special case and
is addressed separately in the section above.
++
Gastric acid and pepsin are major factors in the final pathway
leading to mucosal damage. Therefore, acid-suppressing or buffering
therapy is often important in the management of gastritis and of
peptic ulcer disease, but not always. Proton pump inhibitors (PPIs)
are generally recommended treatment of acid peptic disorders, and
as part of H pylori eradication therapy. The length
of therapy depends upon the etiology and severity of the disease,
but initial PPI therapy usually should not exceed 2 months. H2-receptor
antagonists (eg, ranitidine, cimetidine, famotidine) are also commonly
used in children. However, they are of lower efficacy than PPIs,
and their major drawback is the tolerance that develops, often within
a few weeks.129,130 Antacids may relieve occasional
dyspepsia, but they are not useful for treatment of significant
disease. Chronic use of acid suppression therapies (proton pump
inhibitors or H2-receptor antagonists) may increase rates of community-acquired
pneumonia in adults and children, Clostridium difficile infection
in adults, bacterial gastroenteritis in adults, gastroenteritis
in children, candidemia and necrotizing enterocolitis in preterms,
and vitamin B12 deficiency in adults over 65 years.131-137
++
Sucralfate is a complex of aluminum and sulfated sucrose that
has very little acid-neutralizing ability. It is occasionally used
for children with large areas of oozing from the stomach, or in
children where duodenogastric reflux is thought to be a cause of
symptoms. In children with renal failure, aluminum may be inadequately
excreted; therefore, aluminum levels should be monitored closely,
or, better yet, sucralfate use should be avoided.
++
When appropriate, specific treatment of the underlying cause
of the mucosal injury should be administered. For example, the key
management strategy for stress-induced gastritis is treatment of
the underlying acidosis, hypoxemia, or sepsis. Traumatic gastropathy
requires supportive therapy as well as attention to the underlying
cause of forceful emesis. Crohn disease or eosinophilic gastritis
is treated with immune modulation.
++
Diet plays little role in the prevention or treatment of acid
peptic disease. In some patients, it may be useful to exclude beverages causing
increased acid secretion, such as tea, coffee, and cola. Bland diets
are not of any proven benefit in the treatment of peptic ulcers
and serve only to diminish quality of life. There is no need specifically
to exclude spicy foods from the diet, unless the patient complains
that these cause symptoms; the same principle applies to other foods.
++
The major complications of gastritides are bleeding, which is
either diffuse or in the case of peptic ulcer disease may be focal
and severe; perforation that sometimes penetrates into an adjacent
organ (eg, pancreas); and distortion of the antrum or pylorus or
duodenum, which results in varying degrees of gastric outlet obstruction.138 Other
complications such as hypoalbuminemia or B12 deficiency
are observed in specific disorders as discussed above.
++
Bleeding is treated with endoscopic therapy or surgery as discussed
in Chapter 387. Treatment of scarring and
distortion of the gastric outlet may require endoscopic dilation139 or,
rarely, surgery.