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386 SECTION VI Gastrointestinal Disease
ulcers, specifically those associated with H. pylori infection, will heal
with 14 days of PPI treatment, which is part of H. pylori treatment
itself. Complicated ulcers, however, necessitate a longer treatment of 8
to 12 weeks. NSAID-induced ulcers should be treated for a minimum
of 8 weeks if the NSAID is stopped. Idiopathic ulcers must be evaluated as previously mentioned. Patients with ZES will need treatment
as outlined later.
Maintenance Treatment
In addition to detailed evaluation of the etiology of ulceration for each
individual patient and treatment according to the root cause of PUD
(i.e., H. pylori infection, NSAIDs, ZES), some patients will require
maintenance therapy to prevent ulcer recurrence.
After eliminating risk factors for PUD, patients with the following high-risk characteristics may benefit from antisecretory therapy
with a PPI: (1) giant ulcer (>2 cm) and age older than 50 or multiple
comorbidities, (2) H. pylori–negative ulcer disease, (3) non-NSAID
disease, (4) refractory peptic ulcers defined as ulcers that do not heal
after 12 weeks of PPI treatment, (5) H. pylori eradication failure, (6)
recurrent peptic ulcer, (7) continued NSAID use. Maintenance therapy regimens include either an H2RA or a PPI at the lowest possible
therapeutic dose. The risks of chronic PPIs versus the likelihood of
developing PUD should be reviewed periodically.
Special Considerations
Patients that require dual antiplatelet therapy, specifically aspirin
and clopidogrel, for treatment after cardiac catheterization, unstable
angina, NSTEMI or stroke tend to be co-treated with PPIs to reduce GI
side effects. Both PPIs and clopidogrel are metabolized by CYP2C19,
leading to concerns that PPIs may decrease the efficacy of clopidogrel
and lead to catastrophic events. This risk, however, has been assessed
by various systematic reviews and, although the research obviously
shows that PPIs decrease the risk of GI events, it has not demonstrated
a clear adverse effect on patients on clopidogrel.
Additionally, new anticoagulants, such as dabigatran, rivaroxaban, apixaban, and edoxaban, are becoming more commonly used
in patients who need long-term anticoagulation. Though research on
these drugs and GI bleeding as it relates specifically to PUD is lacking, these drugs are linked to increased risk of GI bleeding overall and
likely lead to increased bleeding in patients with PUD.
Surgery
The efficacy of nonsurgical ulcer treatment has increased dramatically
with the discovery of H. pylori eradication treatment and antisecretory
therapy. As a result, surgery is rarely used to treat PUD. It is an important therapeutic option, however, for patients with complications, such
as gastric outlet obstruction, bleeding and perforation.
Complications of PUD
The most common complications of PUD include bleeding, perforation, and obstruction, with bleeding being the most common and
obstruction being the least common.
Bleeding
GI bleeding accounts for half a million hospitalizations per year and
about $5 billion in annual costs in the United States. Upper GI bleeds
(UGIBs) make up half of those hospitalizations and carry a significant
mortality rate of up to 7.4%. Peptic ulcers are the most frequent cause
of UGIBs, making up about a third of all cases.
Bleeding ulcers present with the classic symptoms of an UGIB and
vary depending on the severity of the bleed. In chronically bleeding
UGIB, patients present with occult blood in the stool and possibly
iron deficiency anemia. When the bleed is acute, patients will have
coffee-ground emesis and melena (black and tarry stool); however, a
patient with a brisk UGIB may present with hematemesis and, possibly, hematochezia with hypotension. Treatment of bleeding ulcers
includes fluid resuscitation, blood transfusions when hemoglobin
levels fall below 7 g/dL or below 8 g/dL in patients with existing cardiovascular disease or who are symptomatic, intravenous PPI therapy
(which should be switched to oral therapy as soon as the patient tolerates oral medications), and an esophagogastroduodenoscopy (EGD)
within 24 hours of admission. If the patient has high-risk clinical features, such as hemodynamic instability or hematemesis, EGD should
be performed within 12 hours of admission. Endoscopic intervention
is dictated by the features of the bleeding ulcer. Typically, endoscopic
interventions, such as injections, sclerotherapy, or clips, are employed
if there is active bleeding from the ulcer, or if there is a clot adherent
to the ulcer. In active bleeding, combination therapy such as injected
epinephrine followed by the application of clips produces improved
outcomes over a single modality. Hospital discharge is dependent on
the patient’s clinical status, but it is typically after 3 days of hospitalization for patients with high-risk bleeds.
Perforation
Perforation of a peptic ulcer accounts for 2% to 10% of ulcer complications. Perforation happens when an ulcer penetrates the full thickness
of the stomach or duodenal wall. It should be suspected if a patient
develops sudden, severe abdominal pain. On physical examination,
the patient will have exquisite abdominal pain and tenderness, guarding, and, potentially, signs of peritonitis such as rebound tenderness.
Upright chest and abdominal radiographs will show free peritoneal air
under the diaphragm; however, if they do not, and the clinical suspicion for perforation is high, the next most useful imaging modality, if
the perforation happened within the previous 6 hours, is ultrasound.
After 6 hours have elapsed, CT may provide diagnostic value.
Patients with an abdominal perforation need to be treated for
hemodynamic instability and receive antibiotics targeting enteric
bacteria. Additionally, they should undergo an emergent surgical
evaluation. Risks of surgery must be weighed against the individual
patient’s risk of perforation-related mortality. However, nonoperative management is appropriate only for a small number of patients,
and the most effective treatment remains surgical repair of the
perforation.
Gastric Outlet Obstruction
Though much less common than UGIB and perforation, gastric outlet
obstruction (GOO) is a serious complication of a peptic ulcer located
at the pylorus. Though PUD historically accounted for the majority
of cases of obstruction, the incidence of GOO in PUD has declined
as treatment for PUD has steadily improved. Currently, the leading
cause of GOO is malignancy, therefore malignancy must be ruled out
by endoscopy in all cases.
The precise etiology of GOO is unknown; however, it is more prevalent in patients with duodenal or pyloric ulceration. Causes of GOO
secondary to PUD are likely multifactorial, from inflammatory-related
causes such as spasm, edema, and pyloric dysmotility in the acute setting to more chronic causes such as scarring and fibrosis as the ulcer
heals.
Patients with GOO present with early satiety, nausea, bloating,
vomiting, and weight loss. On physical exam, patients will have stigmata of dehydration, abdominal distention, and a succussion splash.
At presentation, patients should undergo gastric decompression to
clear the gastric contents, and electrolyte abnormalities must be evaluated and treated along with IV rehydration.
CHAPTER 37 Diseases of the Stomach and Duodenum
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387
Radiographic imaging will demonstrate an enlarged gastric bubble and dilated proximal duodenum on abdominal radiographs.
Computed tomography of the abdomen will generally show gastric
distention and retained chyme in the gastric cavity with an associated
fluid level (Fig. 37.6).
Ultimately, patients must undergo EGD for diagnostic and possible therapeutic purposes (Fig. 37.7). Endoscopic biopsies must be
obtained from the site of obstruction to evaluate for malignancy and
from the antrum and body to determine if there is underlying H. pylori
infection. If PUD is suspected, antisecretory IV treatment with a PPI
must be initiated to promote healing of the ulcer and alleviation of the
obstruction. Oral alimentation must be introduced slowly, as tolerated
by the patient. Patients with refractory obstruction who fail conservative treatment may be treated endoscopically with balloon dilation,
endoscopic stent placement, or even surgery. Additionally, patients
should receive treatment for H. pylori and other causes of PUD, if
indicated.
ZOLLINGER-ELLISON SYNDROME
Definition and Epidemiology
ZES is a rare condition that results from ectopic gastrin secretion due
to a neuroendocrine tumor, called a gastrinoma. This leads to elevated
levels of basal acid secretion in the stomach. Symptoms such as multiple or H. pylori–negative duodenal ulcers, recurrent ulcers, refractory
ulcers, esophagitis, and unexplained diarrhea should raise clinical suspicion of ZES. Gastrinomas are primarily located in the duodenum
(60% to 80%) or pancreas (10% to 14%) in an area known as the “gastrinoma triangle.” They are also rarely found in other areas such as the
stomach, liver, bile duct, and ovary. ZES tends to present in patients
between 45 and 50 years old, and there is a slight male predominance
with an estimated male to female ratio of 2:1 to 3:2. The diagnosis is
often delayed due to low clinical suspicion.
Although the majority of ZES cases develop sporadically, 10% to
54% of ZES cases are found in patients with multiple endocrine neoplasia type 1 (MEN1). Multiple endocrine neoplasia type 1 is an autosomal dominant genetic disorder, usually of the menin gene located
on chromosome 11q13. In addition to gastrinomas, patients with
MEN1 also have increased incidence of parathyroid hyperplasia, pancreatic endocrine tumors, pituitary adenomas, and adrenal adenomas.
Therefore, patients diagnosed with ZES must be screened for MEN1.
Pathophysiology of ZES
The main pathologic characteristic of ZES is excessively elevated levels of circulating gastrin, secreted autonomously from gastrinomas.
Unlike physiologic gastrin production, gastrin release from gastrinomas is not subject to regular inhibitory feedback loops. This unregulated acid secretion causes excessive acid secretion that eventually leads
to peptic ulceration in 90% of people with ZES. Exaggerated gastrin
levels also act as trophic factors for ECL and parietal cells resulting in
hypertrophic gastric rugae that are visible on endoscopy.
Fig. 37.6 Transverse view of an abdominal CT demonstrating a gas-
tric outlet obstruction with significant narrowing at the distal stomach
(arrow). This has caused gastric distention with retained fluid in the
stomach and a visible fluid level. (From Mönkemüller, et al. Gastrointestinal Endoscopy 2012;75:463-465.)
Fig. 37.7 Endoscopic appearance of gastric outlet obstruction due to a pyloric channel stricture. (A) Pyloric
channel stricture. (B) Endoscopic view of balloon dilation of the pyloric stricture. (C) Post-procedure view of the
pylorus after successful balloon dilation. (From Kochhar et al. Gastrointestinal Endoscopy 2018;8:899-908.)
Clinical Presentation
In addition to an elevated risk of PUD, as detailed above, a third of
patients may present with unexplained diarrhea, which can sometimes
lead to electrolyte imbalances such as hypokalemia, steatorrhea, and
weight loss. Diarrhea may be the sole clinical manifestation in about
20% of patients. Diarrhea occurs when the high acid load reaches
the small intestine causing direct enterocyte damage, inactivation of
pancreatic lipase, and precipitation of bile acids, which interferes with
micelle formation.
CBA
388 SECTION VI Gastrointestinal Disease
Other manifestation of ZES include esophageal syndromes from
gastric acid hypersecretion, such as dysphagia, esophagitis, esophageal
ulceration, strictures, or even perforation. In fact, reflux esophagitis
may occur in up to 40% of patients with ZES.
Diagnosis
As in the diagnosis of other rare diseases, the most important factor in diagnosing ZES is having a high index of suspicion for ZES in
patients that present with classic symptoms, as detailed above. These
classic symptoms, however, may be hard to discern in the age of ubiquitous PPI use because these antisecretory agents may mask ZES symptoms. Diagnosis of ZES requires the presence of hypergastrinemia and
hyperchlorhydria.
Initially, patients with suspected ZES should be evaluated by
obtaining a fasting gastrin level and obtaining a gastric pH. A low gastric pH in conjunction with high gastrin levels is characteristic because,
in achlorhydric states, gastrin will be appropriately elevated but so will
pH. Because PPIs also affect the gastric pH, PPIs must be discontinued
for at least 1 week prior to testing. PPI discontinuation in patients with
ZES incurs serious risks and should be done only after careful evaluation of the risks and benefits of PPI withdrawal for diagnostic purposes
under the supervision of experienced practitioners. Some case reports
have described serious health complications of ZES that developed just
48 hours after PPI withdrawal.
Gastrin levels greater than ten times the upper limit of normal
(ULN) with a gastric pH less than 2 establishes the diagnosis of ZES.
However, most patients with ZES will have equivocal gastrin levels. A
secretin stimulation test can help make the diagnosis in this case.
The secretin stimulation test takes advantage of the paradoxical
increase in gastrin secretion after the administration of secretin in
patients with gastrinomas. Similar to gastrin and gastrin pH levels, the
secretin test must be obtained while the patient is not under antisecretory therapy. Gastrin levels are obtained before and after the administration of 2 U/kg of secretin. The test is positive if gastrin levels increase
at least 120 pg/mL with secretin administration.
After the diagnosis of ZES is made, all patients must be screened
for MEN1 by measuring calcium, parathyroid hormone (PTH), and
MEN1 germline mutation testing. In addition, first-degree relatives
of patients with MEN1 also must be screened. Because a majority of
gastrinomas are malignant, it is critical to attempt to localize the gastrinoma with the purpose of tumor resection.
A useful imaging modality for localizing gastrinomas is a somatostatin-receptor scintigraphy (SRS) scan combined with CT scan, but
other modalities such as CT, MRI, and ultrasonography may also be
used. In experienced hands, upper endoscopy with endoscopic ultrasound (EUS) has similar sensitivity to SRS (74% and 75% respectively)
and can be helpful in determining the location of the gastrinoma.
Treatment of ZES
After ruling out other causes of hypergastrinemia (such as pernicious
anemia or PPI-induced hypergastrinemia, in which the high gastrin
occurs secondary to low acid secretion), the most important treatment
goal for ZES is reduction and normalization of acid secretion, which
can be achieved through PPI therapy. To control acid secretion in ZES,
PPIs typically need to be taken at elevated doses, sometimes double
the standard dose or higher. PPI treatment must be titrated to achieve
a basal acid output (BAO) that is less than 10 mmol/hour the hour
preceding the next scheduled dose. When patients are unable to take
oral medications, IV PPI therapy must be administered to control acid
secretion. In extreme cases, vagotomy may be performed to decease
acid secretion.
Surgery can sometimes uncover a hitherto unrecognized primary
tumor. Additionally, it allows for evaluation of tumor grade and stage
and removes the source of the ectopic gastrin production. Regardless,
surgery significantly improves survival rates in patients with ZES.
Gastrinomas tend to metastasize via a hematogenous route primarily
to the lymph nodes, followed by the liver. Up to 50% of patients will
have liver metastases at presentation.
GASTRITIS
Gastritis is a general term that is used to describe inflammation in the
gastric mucosa. Gastric inflammation can be caused by a variety of
conditions, most commonly H. pylori infection and NSAID gastritis
(more strictly in the latter case termed gastropathy, because inflammation is rather mild). Gastritis can be acute or chronic and may be secondary to other infectious causes, autoimmune disorders, drugs, and
ischemia. Every effort should be made to identify the cause of gastritis,
though many times a specific diagnosis may not be identifiable.
Atrophic gastritis is a histopathologic entity of glandular loss that
results from chronic inflammation. It can be divided into two major
types: multifocal (secondary to environmental factors, H. pylori,
specific diets) or corpus predominant (autoimmune) gastritis. This
section will focus on the corpus predominant subtype, autoimmune
metaplastic atrophic gastritis (AMAG).
AMAG is a chronic inflammatory gastritis caused by autoantibodies against intrinsic factor and the parietal cells in the fundus and
body. It has a prevalence of 2% with a female to male ration of 3:1,
and it is more common in persons with other autoimmune diseases,
specifically diabetes mellitus and autoimmune thyroid disease. AMAG
increases the risk of intestinal-type gastric adenocarcinoma and gastric carcinoid tumors. Patients typically present with nonspecific GI
symptoms and are generally diagnosed relatively late in their disease,
once they have hematologic manifestations, such as macrocytic anemia
due to vitamin B12 deficiency (pernicious anemia). Due to the inability
to absorb vitamin B12, these patients may present with concomitant
neurologic and psychiatric symptoms, though this happens in less than
10% of cases. On biopsy, patients will have gastric body mucosal atrophy as well as ECL hyperplasia in the setting of hypochlorhydria (and
resultant hypergastrinemia). Treatment consists of vitamin B12 supplementation and surveillance for associated diseases.
Infectious gastritis may be caused by infections other than H.
pylori, such as CMV, Mycobacterium avium-intracellulare, enterococcal
infections, HSV, as well as parasitic and fungal infections. Treatment
for infectious gastritis involves treatment of the specific microbe causing damage to the gastric mucosa.
Eosinophilic gastritis (EG) is a part of a continuum of eosinophil-associated gastrointestinal disorders (EGIDs). It is associated
with systemic eosinophilia in about 75% of patients with EGID. In EG,
there is an eosinophilic infiltration, which rarely includes all layers of
the gastric wall. There is mucosal involvement in 60% of cases, muscular involvement in 30% of cases, and subserosal involvement in 10% of
cases. Diagnosis is difficult, given the varying locations of infiltration,
and the nonspecific appearance of the stomach on EGD. Eosinophilic
gastritis may be a cause of GOO. Treatment includes systemic steroids;
however, there has been some success treating patients with elemental
diets free of allergenic foods.
Ménétrier’s disease is a very rare condition associated with hypertrophy of the gastric mucosa primarily in the body of the stomach.
Histologically, there is proliferation of the gastric glands with cystic
dilation of the basilar portion. The etiology of the disease is unknown,
and the diagnosis is difficult to make. Diagnosis generally necessitates
Management of patient with unexplained dyspepsia
Yes
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Age ≥60?
CHAPTER 37 Diseases of the Stomach and Duodenum
No
389
EGD showing
organic cause for
dyspepsia?
Yes
Management dependent
on pathology on EGD
Fig. 37.8 Guideline for management of patients with dyspepsia. EGD, Esophagogastroduodenoscopy; TCA,
tricyclic antidepressant. (Adapted from Moayyedi PM, Lacy BE, Andrews CN, Enns RA, Howden CW, Vakil
N. ACG and CAG Clinical Guideline: Management of Dyspepsia. Am J Gastroenterol. 2017;112:988-1013.)
No
+ –
Treat and
eradicate
H. pylori
Symptom
cessation
Successful treatment
evaluation of the gross appearance of the gastric mucosa during
endoscopy along with the characteristic constellation of symptoms.
Clinically, there is associated nausea, vomiting, anemia, hypochlorhydria, and peripheral edema secondary to hypoalbuminemia.
Lymphocytic gastritis is another rare disorder characterized by
mucous and gastric epithelium infiltration by T cells. It is associated with celiac disease, H. pylori gastritis, collagenous colitis, and
Ménétrier’s disease.
FUNCTIONAL (NONULCER) DYSPEPSIA
When a patient presents with a constellation of symptoms similar to
that of PUD or gastritis without evidence of ulceration on EGD, they
are said to have nonulcer dyspepsia (NUD). Nonulcer dyspepsia is a
diagnosis of exclusion. The etiology of NUD is not well understood;
however, patients with NUD may have impaired gastric mucosal
integrity, dysmotility, dysregulation of the gut-brain axis, or sensory
dysfunction. Psychosocial factors and psychiatric disorders such as
depression and anxiety, however, are very strongly associated with
NUD. NUD affects 10% to 30% of the world’s population.
Specific diagnostic criteria include bothersome postprandial fullness, early satiety, epigastric pain, or epigastric burning, in addition to
a lack of evidence of an organic or structural explanation of the symptoms on EGD, imaging, or laboratory studies. Patients older than 60
years of age should have an EGD to evaluate for possible malignancy.
Depending on individual clinical symptoms, some patients may benefit from motility studies to evaluate for dysmotility and gastroparesis
(Fig. 37.8).
Unfortunately, treatment for NUD is limited and therapeutic
modalities have not been well studied. Some (about 1 in 10) dyspeptic
patients with NUD who test positive for H. pylori may respond to H.
Non-invasive test for
Continuation of symptoms
Symptom cessation
Symptom cessation
Symptom cessation
Symptom cessation
H. pylori
Trial of PPI
Continuation
of symptoms
Trial of TCA
Continuation
of symptoms
Trial of prokinetic
Continuation
of symptoms
Consider psychotherapy
pylori eradication even if they do not have evidence of PUD on endoscopy. Antisecretory therapy with a PPI or H2RA is recommended
for H. pylori–negative patients and those that have been successfully
treated for H. pylori who continue to have symptoms. Tricyclic antidepressants are recommended for patients that continue to be symptomatic despite H. pylori eradication and antisecretory therapy. Further
treatment options include prokinetics, such as cisapride and domperidone, though these are not available in the United States. Patients who
do not respond to therapy and have ongoing, bothersome symptoms
may benefit from psychological therapies, the most common being
cognitive behavioral therapy.
CYCLIC VOMITING SYNDROME
Cyclic vomiting syndrome (CVS) is an idiopathic condition that presents both in children and adults with the mean age of presentation
of 37 years in the adult population. The etiology of CVS is largely
unknown, but it has been observed to be triggered in patients with
chronic cannabis use, migraine headaches, and by certain foods (which
typically also trigger migraine headaches). Characteristically, patients
present with bouts of vomiting lasting hours to days with absence of
vomiting between episodes. Adult patients will commonly report alleviation of symptoms while taking hot showers or baths.
Diagnosing CVS is difficult, and many years may elapse before a
clear diagnosis is made. Clinicians may often misdiagnose patients
with recurrent infectious gastroenteritis or other self-limiting causes of
vomiting. Specific criteria for diagnosis include (1) stereotypical bouts
of acute vomiting lasting less than 1 week, (2) three or more episodes
in the prior year and two in the past 6 months, occurring at least 1 week
apart, (3) absence of vomiting between episodes. The diagnosis of CVS
must be made only after excluding other possible diagnoses.
390 SECTION VI Gastrointestinal Disease
In the acute setting, therapy is supported with IV fluids, antiemetics, and slow reintroduction of food as tolerated by the patient.
Antiemetics taken prior to the attack during the prodromal period
may prevent or reduce the longevity of symptoms. Maintenance therapy consists of avoidance of triggers and, if appropriate, psychosocial
treatment. When a patient presents with CVS in the setting of cannabis
use, cannabis use must be stopped.
RAPID GASTRIC EMPTYING
Rapid gastric emptying, also known as dumping syndrome, is a debilitating condition manifesting in postprandial gastrointestinal and vasomotor symptoms that occur following esophageal, gastric, or bariatric
surgery. It is due to premature delivery of food into the small intestine.
Postsurgical rapid gastric emptying occurs in 25% to 50% of cases with
5% to 10% of patients experiencing debilitating symptoms; however,
this diagnosis is also correlated with diabetes mellitus, and idiopathic
cases have also been reported. Rapid gastric emptying can be divided
into two categories, early and late dumping syndrome, of which the
early variation is most common. It is defined as less than 30% retention
of gastric contents within 1 hour of solid meal ingestion.
In early rapid gastric emptying, hyperosmolar food is delivered to
the small intestine triggering the release of vasoactive substances such
as neurostatin, vasoactive intestinal peptide (VIP), and glucose modulators such as incretins, insulin, and glucagon. This results in gastrointestinal symptoms such as early satiety, pain, diarrhea, nausea, cramps,
and bloating, vasomotor symptoms such as hypotension, and sympathetic nervous system response such as facial flushing, palpitations,
and diaphoresis within 30 minutes of meal ingestion.
The symptoms of late gastric emptying are a result of hyperinsulinemia and subsequent reactive hypoglycemia. Hyperinsulinemia occurs
secondary to an increased release of incretins in response to undigested
carbohydrates in the small intestine. Symptoms, including diaphoresis, tremulousness, decreased concentration, and altered levels of consciousness, occur 1 to 3 hours postprandially. Early and late gastric
emptying may be present in isolation, but they frequently coexist.
Diagnosis of rapid gastric emptying primarily relies on a high clinical suspicion in patients with typical clinical symptoms of rapid gastric
emptying. Other diagnostic modalities include oral glucose tolerance
test and radionuclide scintigraphy.
First-line treatment includes lifestyle modifications to reduce the
amount of food taken per meal, eating at more frequent intervals, and
separating solid from liquid food ingestion. Additionally, it can be helpful to lie down after meals and decrease carbohydrate and lactose ingestion. Early consultation with a dietitian is important to ensure that an
adequate nutritional status is maintained. When lifestyle modification
methods fail to alleviate symptoms, pharmacologic options include
acarbose, guar gum, or symptomatic treatment with loperamide, tincture of opium, and other methods of pain control. Octreotide, which
inhibits the secretion of vasoactive agents, may also be helpful.
GASTROPARESIS
Gastroparesis occurs when there is delayed gastric emptying into the
small intestine, causing a characteristic constellation of symptoms. It is
most commonly seen in diabetics, postsurgical patients, and those on
chronic scheduled opioid therapy. A third of cases are idiopathic, and
women are more likely than men to develop this disorder. Up to 30%
to 50% of patients with type 1 diabetes have delayed gastric emptying,
as do 15% to 30% of patients with type 2 diabetes.
Diabetic gastroparesis is better understood than idiopathic gastroparesis. The etiology of diabetic gastroparesis is similar to that of
diabetic neuropathy with possible denervation of the vagus nerve
causing a delay in gastric emptying. Additionally, patients with diabetes-related gastroparesis have been found to have decreased numbers of interstitial cells of Cajal (ICCs), the pacemaker cells of the GI
tract, as well as decreased levels of nitric oxide release from enteric
neural cells. Although patients with idiopathic gastroparesis also have
decreased numbers of ICCs, the cause of idiopathic gastroparesis is less
well understood, though enterovirus infections have been implicated.
Clinically, patients experience early satiety, abdominal distension,
nausea, vomiting, anorexia, and malnutrition. Though all patients
with gastroparesis experience nausea, patients with diabetes tend to
have more severe and more frequent episodes of vomiting when compared to those with idiopathic gastroparesis. Patients with idiopathic
gastroparesis are more likely to have severe postprandial fullness and
early satiety.
Some patients with idiopathic gastroparesis are misdiagnosed as
having nonulcer dyspepsia, therefore a high index of suspicion is key
to the diagnosis. After gastric outlet obstruction has been ruled out,
the timing of gastric emptying may be evaluated with gastric emptying
scintigraphy, breath testing, or a wireless motility capsule. It is very
important that patients refrain from taking prokinetic or gastroparetic
agents prior to these studies.
Treatment takes a stepwise approach beginning with dietary modifications (small, spaced out meals), improving glucose control in diabetic patients, and adding prokinetic agents. More invasive procedures
such as gastric pacemakers may be tried in severe cases.
GASTRIC VOLVULUS
Gastric volvulus is a rare condition that affects both adult and pediatric patients, where the stomach rotates at least 180 degrees along its
transverse or longitudinal axis causing gastric inlet or outlet obstruction. In extreme cases, gastric volvulus may cause strangulation,
necrosis, and perforation; therefore it is considered a surgical emergency. The mortality rate for acute gastric volvulus ranges between
15% to 20%, whereas it is 0% to 13% for chronic cases. Rotation of
the stomach is generally caused by paraesophageal hernias, structural
abnormalities (such as neoplasms), adhesions, and gastric ligamentous laxity (Fig. 37.9).
Clinically, presentation varies depending on acuity and degree of
obstruction. Borchardt triad of acute abdominal pain, severe retching
without vomiting, and inability to place a gastric tube is present in 70%
of cases with acute gastric volvulus. If the volvulus is severe enough to
cause strangulation and necrosis, hematemesis may be seen. Patients
with chronic gastric volvulus may present with vague symptoms such
as abdominal pain, dysphagia, and bloating. These may be misdiagnosed as other upper GI disorders.
Given the rarity and nonspecific presentation of gastric volvulus, diagnosis is often done while investigating other causes for the
patient’s symptoms. Evidence of gastric outlet obstruction with
an interruption, such as two pockets of air-fluid levels, is seen on
radiographs. Additionally, given the correlation with esophageal
hernias, these can also be seen on radiographs and should increase
index of suspicion for gastric volvulus. These patients typically have
subsequent abdominal CT scans that show abnormal location of the
antrum and evidence of GOO.
Treatment can be divided into three categories: conservative, endoscopic, or surgical. In the acute setting, patients must be treated and
CHAPTER 37 Diseases of the Stomach and Duodenum
B
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A
Fig. 37.9 The two major types of gastric volvulus. (A) Organoaxial vol-
vulus, in which there is anterior rotation about the cardiopyloric axis,
resulting in an upside-down stomach with the greater curve on top and
the lesser curve on the bottom. Obstruction may occur at the gastroesophageal junction and the pyloroantral area. (B) Mesenteroaxial volvulus, in which there is anterior rotation about an axis perpendicular to
the cardiopyloric axis. The greater curve remains on the bottom. (From
Tsang, Tat-Kin et al. Endoscopic reduction of gastric volvulus: The alphaloop maneuver Gastrointestinal Endoscopy 1995; 42: 244-248.)
391
stabilized. Conservative therapy consists of placing a gastric tube and
laying patients in the prone position. It is generally reserved for stable patients with viable stomach tissue at the time of presentation. An
endoscopic approach affords therapeutic and diagnostic value because
it can assess the condition of the gastric mucosa and may sometimes
lead to resolution of the volvulus with insufflation. Critically ill patients
with evidence of tissue compromise generally must undergo surgery
to relieve the volvulus and resect damaged tissue. Surgery also repairs
gastric perforations and hiatal hernias. Patients generally undergo a
gastropexy (fixation of the stomach to the anterior abdominal wall) to
prevent future episodes.
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38
Inflammatory Bowel Disease
Talha A. Malik, Michael F. Picco, Francis A. Farraye
INTRODUCTION
Inflammatory bowel disease (IBD) comprises two chronic disorders:
ulcerative colitis (UC) and Crohn’s disease. The diagnosis of IBD is
based on review of clinical, endoscopic, radiologic, and histologic data.
Although the cause of these two diseases has yet to be defined, new and
emerging targeted anti-inflammatory treatments hold great promise
in helping to reduce morbidity and improve the quality of life of individuals with IBD.
UC is characterized by chronic inflammatory changes that involve
the colonic mucosa in a continuous superficial fashion, typically starting in the rectum and extending proximally. Depending on the extent
of the disease, UC can be divided into proctitis (rectum only), proctosigmoiditis (rectum and sigmoid), left-sided colitis (extending to the
splenic flexure), and pancolitis (inflammation extends proximal to the
splenic flexure). This classification is significant for both prognosis
and therapy. Unlike UC, Crohn’s disease can involve any segment of
the gastrointestinal tract from the mouth to the anus, often in a discontinuous fashion. It is characterized by transmural chronic inflammation, which results in complications such as abscesses, fistulas, and
strictures.
Historical Perspective
Ulcerative colitis was first described in ancient Greece by Hippocrates
as a condition characterized by chronic diarrhea and bloody stools. In
1859, Samuel Wilks, a British physician, described “ulcerative colitis”
as a discrete disease entity.
In 1913, the British physician Kennedy Dalziel first described
patients with transmural inflammation of the small and large intestines. Subsequently, in 1932, Dr. Burrill Crohn, Dr. Leon Ginzburg,
and Dr. Gordon Oppenheimer published papers describing a condition that caused inflammation of the terminal ileum and which they
called regional or terminal ileitis. This disease entity later began to be
referred as Crohn’s disease.
The first breakthrough that established IBD as the major intestinal autoimmune disease occurred in the 1950s when it was demonstrated that symptoms in patients with both UC and Crohn’s disease
responded to corticosteroids. In the 1980s, traditional immune modulators, mainly thiopurines, were used as first-line steroid sparing
agents. In 1997, Targan and colleagues published findings from the
“Crohn’s Disease cA2 Study” that looked at the efficacy of infliximab,
a biologic antibody against tumor necrosis factor (TNF) cA2 in the
induction of remission in luminal Crohn’s. This began the era of biologics. During the first decade of the 21st century, biologics given intravenously or as subcutaneous injections emerged as the most effective
therapeutic agents used to induce and maintain remission in moderate
to severe UC and Crohn’s disease. Since then, new oral agents are now
available and effective in the treatment of patients with IBD.
EPIDEMIOLOGY
There is variation in the incidence and prevalence of UC and Crohn’s
disease across the globe based on geographic region, particular environment, immigration trends, and ethnic group. In the past, UC was
generally considered to be slightly more common. However, this trend
has changed with the rising incidence of Crohn’s disease. It is estimated
that there are more than 2 million people with IBD in North America.
The annual incidence in North America of both UC and Crohn’s disease is estimated to be between 0 to 20 per 100,000 persons. The estimates for prevalence of UC and Crohn’s disease in North America are
35 to 250 per 100,000 and 25 to 300 per 100,000, respectively. The incidence and prevalence of IBD reflect the interplay of complex genetic
and environmental factors that contribute to these disorders. For
example, both diseases are more common in northern climates and
among white individuals, particularly among populations of European
descent living in North America, South Africa, and Australia. Although
incidence rates of IBD are lowest among Hispanic and Asian populations, IBD can occur in any ethnic or racial group from anywhere in
the world. The cause of IBD remains unknown, but it is believed to
result from a combination of genetic, immunologic, infectious, and
environmental factors. In addition, research points toward a relationship between the human microbiome and dysfunction of the immune
system in patients with IBD.
UC and Crohn’s disease can occur at any age, but the peak age of
onset for UC is between 30 and 40 years of age and for Crohn’s disease
it is between 20 and 30 years. There is another peak, especially for UC,
between 60 and 70 years of age based on studies in several European
cohorts. The incidence and prevalence of UC and Crohn’s disease
appear to be similar in North American men and women.
RISK FACTORS AND PATHOPHYSIOLOGY
IBD is likely a result of an uncontrolled immune-mediated inflammatory response in genetically predisposed individuals to an environmental trigger that interacts with the intestinal flora and primarily affects
the alimentary tract.
Approximately 5% to 20% of patients with IBD have a first-degree relative with the disease, and first-degree relatives of IBD
patients have about a 10- to 15-fold increased risk for developing
IBD, predominantly with the same disease as the proband. A positive family history is more frequently observed in patients with
Crohn’s disease compared with UC, suggesting that genetic factors
are more important in the etiology of Crohn’s disease. The lifetime
risk of developing IBD in first-degree relatives has been estimated
at 5% in Crohn’s disease and about 2% in UC among non-Ashkenazi Jewish populations and 8% and 5% within Ashkenazi Jewish
populations, respectively.
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Through genome-wide association studies (GWAS), over 200
genetic loci have been identified as being associated with IBD.
However, there is little diagnostic utility in clinical practice of these
genetic variants due to their overall low incidence in IBD populations.
With increasingly diverse populations being studied, this may change.
Examples of single nucleotide polymorphisms (SNPs) associated
with Crohn’s include sequences in the NOD2, IL23-receptor and the
ATG16L1 genes. It is thought that NOD2 variants may predict more
complicated disease, mainly in European patients with stricturing ileal
and penetrating disease. IL-12 variants may be associated with risk for
early surgery.
Additionally, other genes associated with IBD that have been identified through GWAS include IRGM, LRRK, FUT2, CARD9, TNFSF15,
FCG2RA, NKX2-3, PTPN2, ZNF365, ECM1, STAT3, and IL10R among
others. As mentioned, these variants have little diagnostic or therapeutic utility in clinical practice at this time due to lack of replication of
associations noted in small studies.
Profound alterations in mucosal immunology have been demonstrated in patients with IBD. In the normal immunologic state of the
intestine, activated lymphoid tissue is abundant within the mucosal
compartment. This state has been described as controlled or physiologic inflammation, and it likely develops in response to constant
encounters with antigenic substances (derived from host microbial
flora or dietary and environmental sources) that have crossed the epithelial barrier from the luminal environment. Indeed, one of the main
functions of the intestinal immune system is to discriminate noxious
or harmful substances and organisms from nonharmful ones. As a
result, a large and well-maintained network of many different mucosal immune cells exists, including cells involved in reducing immune
responses (regulatory cells) and those involved in activating immune
responses. In IBD, this homeostatic balance, or immune tolerance, is
dysregulated, resulting in overactivation of the immune system.
In the past, it was thought that inflammation in Crohn’s was predominantly mediated by TH1 cells and in UC it was primarily mediated by TH2 cells; there is now considerable evidence that each of their
pathogeneses is more complex and nuanced, whereby both types of T
helper cells appear to play a role. Furthermore, there is recent evidence
that TH17 cells produce pro-inflammatory cytokines that facilitate
inflammation in IBD, the most notable of which appear to be IL-6 and
IL-17. Moreover, IL-23R is expressed in high numbers on TH17 cells
and has been postulated to play a key role in propagation of inflammation in both UC and Crohn’s disease.
Overall, the immune mechanisms mediating inflammation in IBD
are complex and work through significant interactions with environmental triggers, the genome, and the gut microbiome to produce
active disease necessitating the need for a personalized approach to
management.
As alluded to, environmental factors also are believed to play a role
in the pathogenesis of IBD because the disease is more common in
industrialized countries. Moreover, the frequency has increased in
countries as they become more industrialized. It has been postulated
that poor sanitation, food contamination, and crowded living conditions are associated with helminthic infection, which leads to regulatory T-cell conditioning and stimulation of IL-10 and transforming
growth factor-β production by mononuclear cells, thereby preventing
intestinal inflammation.
The only environmental factor clearly associated with IBD is
tobacco smoking. Tobacco seems to be protective against UC, with an
older age of onset in former smokers. Among UC patients, smoking
cessation may cause an exacerbation. Moreover, studies have shown
that tobacco smokers with UC may have a milder disease course,
require less immune suppression, and have a reduced need for surgery.
Conversely, Crohn’s disease is associated with a more aggressive disease course. Tobacco consumption is associated with a 2-fold
increase in the risk of development of Crohn’s disease and an earlier
age of onset. Passive smoking may also increase the risk. Smoking leads
to more frequent exacerbations of Crohn’s disease, an increased need
for immunosuppression and surgery, as well as a higher risk of postresection recurrence. Not all studies demonstrate these associations,
suggesting a gene-environment interaction of tobacco and IBD with
the divergent effects on UC and Crohn’s disease not well understood.
Diet may also play a role. There is observational evidence that
patients with Crohn’s disease consumed a much higher quantity of
refined sugars represented by sugar, candy, and sweetened foods like
cakes and cookies prior to their diagnosis. Subsequently, it was suggested that high sugar intake itself could also interact with intestinal
flora and produce pro-inflammatory intestinal agents. In addition to
increased intake of refined sugars, newly diagnosed patients with IBD
consumed less dietary fiber, raw fruit, and vegetables when compared
to healthy controls. A systematic review of past epidemiologic surveys
and case control studies performed in Japanese patients suggested an
association between increased consumption of animal meat in addition to carbohydrates as potential risk for development of Crohn’s disease. The researchers hypothesized that Western dietary patterns may
be responsible for the increased occurrence of IBD in Japan.
Study of the relationship between obesity and IBD is especially
important because of credible molecular evidence that links adipose
tissue physiology to intestinal inflammation. However, it is still not
entirely clear whether this link translates into a causal or clinically
meaningful association between obesity and Crohn’s disease.
Recently, there has been interest in understanding the association
between cannabis and IBD. There are no credible epidemiologic data
suggesting that cannabis plays a role in the development of IBD or its
management. However, studies are ongoing.
Medications suggested to be potential risk factors for the development of IBD include, most importantly, nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs have also been implicated in
exacerbating existing disease. Other medications potentially linked to
development of IBD include oral contraceptives, hormone replacement therapy, and antibiotics, but evidence for these is not as strong
as with NSAIDs.
Mycobacterium avium subspecies paratuberculosis has been linked to
Crohn’s disease but this association has not been confirmed. Similarly,
associations between Salmonella, Campylobacter, and measles virus
have been reported to increase the risk of IBD, but not proven.
Poor hygiene (lack of sanitation), especially early in life, may protect against the development of IBD. Other potential associations
include stress, anxiety, depression, disruptive sleep pattern, and sedentary lifestyle. Although provocative, these associations have not been
confirmed in well-designed prospective studies.
CLINICAL PRESENTATION
Intestinal Manifestations
Ulcerative Colitis
UC is characterized by chronic inflammation of the mucosal surface
that involves the rectum and extends proximally through the colon in
a continuous manner. The extent and severity of colonic inflammation
determine prognosis and presentation (insidious vs. acute onset). Most
patients initially exhibit diarrhea, abdominal pain, urgency to defecate,
rectal bleeding, and the passage of mucus per rectum. At presentation,
approximately 40% to 50% of patients have proctitis or proctosigmoiditis, 30% to 40% have left-sided colitis (disease extending to the splenic
flexure), and the remaining 20% to 25% have pancolitis. Though data
394 SECTION VI Gastrointestinal Disease
are variable, depending on the cohort, it has been observed that up
to 50% of patients diagnosed with proctitis or proctosigmoiditis will
progress to more extensive disease by 25 years of follow-up.
The typical clinical course of UC is one of chronic intermittent
exacerbations followed by periods of remission. A disease flare may be
suggested by the development of diarrhea, hematochezia, and abdominal pain, with dehydration, fever, and tachycardia suggesting more
severe disease. Elevated fecal calprotectin, erythrocyte sedimentation
rate (ESR) or C-reactive protein (CRP) level may also indicate a flare.
Anemia commonly occurs and is caused by chronic blood loss from
the involved colonic mucosa as well as bone marrow suppression from
the systemic inflammatory process. Perforation can occur in patients
with severe or fulminant colitis, especially those taking corticosteroids,
and in the setting of toxic megacolon. Toxic megacolon is characterized by gross dilation of the large bowel associated with fever, abdominal pain, dehydration, tachycardia, and bloody diarrhea.
Crohn’s Disease
The clinical presentation of Crohn’s disease depends on the section of
gastrointestinal tract involved and the type of inflammation. Crohn’s
disease can involve any portion of the gastrointestinal tract; the most
common site is ileocecal/ileocolonic (40% of patients), followed
by isolated small bowel disease mostly affecting the terminal ileum
(30%), and isolated colonic involvement (25%). The remaining sites
of Crohn’s disease are rarely (5%) affected in isolation and include the
esophagus, stomach, and duodenum.
Symptoms in Crohn’s disease often include right lower quadrant
abdominal pain, fever, weight loss, diarrhea, and sometimes a palpable
inflammatory mass on physical exam. Hematochezia may be present
with colonic involvement but is less common than in UC. The symptoms can often be present for months or years before a diagnosis is
made, and in children, growth retardation may be the sole presenting
sign. In contrast to UC, the inflammation in Crohn’s disease is transmural and can result in deep ulcerations and the formation of fistulous
tracts. Fistulas may form between different segments of bowel (e.g.,
enteroenteric, enterocolonic) or between bowel and skin (enterocutaneous), bowel and bladder (enterovesicular), or rectum and vagina
(rectovaginal). Over time, as many as 30% to 40% of patients will
develop perianal involvement with fissures, fistulas or abscesses.
Chronic inflammation can cause fibrosis and stricture formation,
which in turn may result in partial or complete intestinal obstruction
with the patient complaining of abdominal pain, distention, nausea,
and vomiting. Strictures can also lead to stasis with subsequent small
intestinal bacterial overgrowth. Small bowel disease may lead to vitamin D deficiency. Extensive ileal mucosal disease may lead to malabsorption of vitamin B12 (resulting in a megaloblastic anemia and
neurologic side effects if not corrected) and malabsorption of bile salts
(resulting in diarrhea induced by unabsorbed bile salts and potential
fat-soluble vitamin deficiency). Depletion of the bile salt pool can lead
to the formation of gallstones. Weight loss may result from generalized malabsorption caused by loss of absorptive surfaces. Chronic fat
malabsorption leads to luminal binding of free fatty acids to calcium;
this allows oxalate, which normally is poorly absorbed because it complexes to calcium in the gut lumen, to be absorbed in the colon. The
increase in oxalate absorption increases the risk for urinary calcium
oxalate stone formation. Patients with an ileostomy or chronic volume
loss from diarrhea are also at increased risk for uric acid stones.
Extraintestinal Manifestations
Although both UC and Crohn’s disease primarily involve the bowel,
they are also associated with inflammatory manifestations in other
organ systems. This reflects the systemic nature of these disorders
TABLE 38.1 Extraintestinal Manifestations
of Inflammatory Bowel Disease
Skin
Pyoderma gangrenosum
Erythema nodosum
Sweet syndrome
Hepatobiliary
Primary sclerosing cholangitis
Cholelithiasis
Autoimmune hepatitis
Musculoskeletal
Seronegative arthritis
Ankylosing spondylitis
Sacroiliitis
Ocular
Uveitis
Episcleritis
Miscellaneous
Hypercoagulable state
Autoimmune hemolytic anemia
Amyloidosis
(Table 38.1). Extraintestinal manifestations can occur in parallel or
independently of disease activity and they can become more difficult
to treat than the bowel disease itself.
The most common extraintestinal manifestation is arthritis, which
is seen in about 9% to 50% of patients and is divided into two major
types: axial and peripheral. Axial arthropathy consists of sacroiliitis or
ankylosing spondylitis and does not parallel activity of bowel disease.
Ankylosing spondylitis occurs in 5% to 10% of IBD patients and manifests with low back pain and stiffness that is usually worse during the
night, in the morning, or after inactivity. Sacroiliitis alone (without
ankylosing spondylitis) is common in IBD (up to 20% of patients) but
in many cases is asymptomatic. Peripheral arthropathy is divided into
type 1 and type 2. Type 1 peripheral arthropathy affects peripheral large
joints. It is an asymmetric, seronegative, oligoarticular, nondeforming
arthritis that may involve the knees, hips, wrists, elbows, and ankles.
This peripheral arthropathy usually parallels disease activity. Peripheral
arthropathy type 2 involves typically metacarpal phalangeal (MCP)
joints, is typically symmetrical, and does not parallel disease activity.
Liver complications of IBD include both parenchymal and biliary
tract diseases. Parenchymal diseases include fatty liver, pericholangitis,
and chronic active hepatitis. Pericholangitis, also known as small-duct
sclerosing cholangitis, is the most common of these diseases. It usually
is asymptomatic, identified only by abnormalities in alkaline phosphatase and γ-glutamyl transpeptidase (GGT) on laboratory tests and histologically by portal tract inflammation and bile ductule degeneration.
Small-duct sclerosing cholangitis may progress to cirrhosis.
Biliary tract disease includes an increased incidence of gallstones
and primary sclerosing cholangitis (PSC). PSC is a chronic cholestatic
liver disease marked by fibrosis of the intrahepatic and extrahepatic
bile ducts. It occurs in 1% to 4% of patients with UC and less often in
those with Crohn’s disease. Overall, about 70% of patients with PSC
have UC. Fibrosis leads to strictures of the bile ducts, which in turn
may lead to recurrent cholangitis (with fever, right upper quadrant
pain, and jaundice) and progression to cirrhosis. In addition, about
10% of patients develop cholangiocarcinoma. Medical or surgical
CHAPTER 38 Inflammatory Bowel Disease
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TABLE 38.2 Differentiating Features of UC and Crohn’s Disease
Ulcerative Colitis Crohn’s Disease
Site of involvement Involves colon only
Rectum almost always involved
Pattern of involvement Continuous Skip lesions
Diarrhea Bloody Usually nonbloody
Severe abdominal pain Rare Frequent
Perianal disease No In 30% of patients
Fistula No Yes
Endoscopic findings Erythematous and friable
Superficial ulceration
Radiologic findings Tubular appearance resulting from loss of haustral
folds
Histologic features Mucosal involvement only
Crypt abscesses
Smoking Protective Worsens course
Serology pANCA more common ASCA more common
ASCA, Anti–Saccharomyces cerevisiae antibodies; pANCA, perinuclear antineutrophil cytoplasmic antibody; RLQ, right lower quadrant.
therapy for IBD does not modify the course of PSC and most patients
progress to cirrhosis and may require liver transplantation.
The two classic dermatologic manifestations that can be associated with IBD are pyoderma gangrenosum and erythema nodosum.
Pyoderma gangrenosum occurs in about 5% of patients and is characterized by a discrete ulcer with a necrotic base, usually on the legs. The
ulcer may spread and become large and deep, destroying soft tissues.
Pyoderma is unrelated to disease activity. Treatment is usually with
systemic or intralesional steroids, or both. Other treatment options
include dapsone, cyclosporine, and anti-TNF agents. Erythema nodosum occurs in 10% of IBD patients, usually with peripheral arthropathy, and produces raised, tender nodules, usually over the anterior
surface of the legs. Erythema nodosum responds to treatment for the
underlying bowel disease. A less common dermatologic manifestation
of IBD is Sweet syndrome or acute febrile neutrophilic dermatosis.
This condition is characterized by the sudden onset of fever, leukocytosis, and tender, erythematous, well-demarcated papules and plaques
that show dense neutrophilic infiltrates on histologic examination.
Ocular manifestations of IBD include uveitis and episcleritis. They
occur in 1% to 5% of patients. Uveitis (or iritis) is an inflammatory
condition of the anterior chamber that produces blurred vision, photophobia, headache, and conjunctival injection that may not parallel
disease activity. Local therapy includes corticosteroids and atropine.
Episcleritis is typically associated with disease activity. It produces
burning eyes and scleral injection without vision deficits and is treated
Fig. 38.1 Endoscopic image of ulcerative colitis demonstrates diffuse
inflammation characterized by erythema, edema, friability, and hemorrhage.
with topical corticosteroids.
and specificity, laboratory testing is of limited value and should not be
DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS
The diagnosis of IBD is based on a constellation of clinical features
and endoscopic, radiographic, and histologic findings. Laboratory tests
are not specific and usually demonstrate inflammation (leukocytosis)
and anemia when the disease is active. Perinuclear antineutrophil
cytoplasmic antibody (pANCA) is positive in up to 70% of patients
with UC but is uncommon in patients with Crohn’s disease, whereas
anti–Saccharomyces cerevisiae antibodies (ASCA) are common (up to
60%) in Crohn’s disease but not typically found in UC (Table 38.2).
Additional markers, mainly for Crohn’s disease, have improved the
sensitivity and specificity of serologic testing, including antibodies to
OmpC (Escherichia coli outer membrane porin C) and antibodies to
bacterial flagellins CBir1, FlaX, and A4-Fla2. Due to lack of sensitivity
used to make a diagnosis of IBD.
Colonoscopy findings in patients with UC are nonspecific, typically
revealing granular mucosa, decreased vascular markings, exudate, and
superficial ulcerations (Fig. 38.1) typically beginning in the rectum.
In more severe cases, the mucosa is friable, with deeper ulcerations.
Patients with long-standing severe disease can develop pseudopolyps, which represent islands of normal tissue in regions of previous
ulceration. In Crohn’s disease (Fig. 38.2), endoscopic examination
may show aphthoid erosions, deep linear or stellate ulcers, edema,
erythema, exudate, and friability with intervening areas of normal
mucosa (skip lesions). However, a diagnosis of indeterminate colitis is
made in 10% to 15% of patients because of an overlap of findings. For
example, colonic Crohn’s disease may produce superficial continuous
rectal involvement similar to that seen in UC. Similarly, chronic UC
Any area of the gastrointestinal tract
Rectum usually spared
Aphthoid and deep ulcers
Cobblestoning
String sign of terminal ileum
RLQ mass, fistulas, abscesses
Transmural
Crypt abscesses, granulomas (about 30%)
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