Transcript Document

Bad Digestion
By Dr. Joel Doughten
A 22-year-old Caucasian woman presents with a complaint of vague
abdominal discomfort. She uses her hand to rub over the upper
abdomen and has a look of discomfort on her face. The pain, described
as burning, occurs at least twice weekly. Last year when she was
pregnant she had a similar but more severe pain. Which of the
following statements is TRUE regarding this patient?
• A:She should undergo upper gastrointestinal endoscopy.
• B:She should be reassured that this is just heartburn and is
nothing to be concerned about.
• C:She should be given a prescription for a proton pump
inhibitor (PPI) because over-the-counter medications are
unlikely to be effective.
• D:Measures such as elevation of the head of the bed, small
meals and not reclining after eating are highly effective.
• E:Intermittent “on-demand” treatment with a PPI is a
useful long-term treatment option.
Answer
• E:Intermittent “on-demand” treatment with
a PPI is a useful long-term treatment option.
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Dyspepsia
Heartburn (dyspepsia) is the most common presenting symptom associated with gastroesophageal acid reflux (GERD). Forty percent of
the U.S. population experience heartburn at least monthly. Most people self-medicate with over-the-counter (OTC) antacids or histamine 2receptor antagonists (H2RAs). A 2007 meta-analysis compared the placebo response, which ranged between 37 and 64 percent to common
OTC agents; the relative benefit increase was up to 41 percent withH2RAs, 60 percent with alginate/antacid combinations (such
asGaviscon®) and 11 percent with antacids alone.
Proton pump inhibitors (PPIs) such as omeprazole/Prilosec OTC® provide greater GERD pain relief at 4 weeks compared
to H2RAs. PPIs appear to have similar clinical effectiveness when compared to one another for treating GERD (SOR A; Ref.
2). Also, PPIs andfundoplication surgery appear to be similarly effective in relieving symptoms and improving quality of life. Even if surgery
is chosen, 10-65 percent of surgical patients still require medications 1 year later.
Empiric therapy is recommended for new dyspepsia patients. Step-up therapy, beginning with a H2RA once or twice daily, then PPIs has
historically been a useful and economical choice. Others favor step-down therapy, beginning with twice-daily PPI for 2 weeks, then H2RA to
maintain symptom-free state. On-demand PPI use in place of continuous daily maintenance therapy was recently shown effective in the longterm management of GERD. Modifications, such as avoiding spicy foods, elevating the head of the bed and avoiding foods before bedtime,
may be helpful for some patients but have not been shown to significantly improve symptoms in all people.
Older patients (55 years of age or older) with new-onset dyspepsia should undergo upper gastrointestinal endoscopy. Other red-flag
indications for endoscopy include anemia, melena,hematemesis, weight loss (>5 percent), persistent vomiting,dysphagia (difficulty
swallowing) and odynophagia (painful swallowing) (SOR C; Ref. 5). These patients have an elevated risk for gastric carcinoma, although
even in this subgroup the prevalence is small. Poor correlation exists between severity of symptoms andendoscopic findings.
Routine endoscopy is not recommended for patients with heartburn alone in the absence of red-flag or alarm symptoms, even if more than
twice weekly. Endoscopy to screen for Barrett’s esophagus is indicated for patients requiring chronic continuous therapy
with PPIs and those with chronic symptoms at risk for Barrett’s esophagus (i.e., duration of symptoms >5 years, white males, ≥50
years of age) (SOR C; Ref. 5).
Selected references:
1. Agency for Healthcare Research and Quality (AHRQ). Comparative Effectiveness of Management Strategies for Gastroesophageal Reflux
Disease.http://effectivehealthcare.ahrq.gov/repFiles/GERD%20Final%20Report.pdf Accessed March 2008
2. Ebell M. All PPIs equivalent for treatment of GERD. http://www.aafp.org/afp/20060101/tips/3.html Accessed March 2008
3. Howden CW, Chey WD. Gastroesophageal reflux disease. J Fam Pract 2003; 52: 240-7.
4. Klok RM, Postma MJ, van Hout BA, et al. Meta-analysis: comparing the efficacy of proton pump inhibitors in short-term use.
Aliment Pharmacol Ther May 15, 2003; 17:1237-45.
5. Medical Advisory Panel for the Pharmacy Benefits Management Strategic Healthcare Group. VHA/DoD clinical practice guideline for the
management of adults with gastroesophageal reflux disease in primary care
practice. http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=5188&nbr=003570&string=GERD Accessed March 2008
6. Pace F, Tonini M, Pallotta S, et al. Systematic review: maintenance treatment of gastro-oesophageal reflux disease with proton pump
inhibitors taken 'on-demand.' Aliment Pharmacol Ther 2007; 26:195-204.
7. Tran T, Lowry AM, El-Serag HB. Meta-analysis: the efficacy of over-the-counter gastro-oesophageal reflux disease therapies.
Aliment Pharmacol Ther 2007; 25:143-53.
True statement(s) about
dyspepsia include(s) which of
the following?
A) Upper abdominal pain not
related to colon function
B) Symptoms may include early
satiety, fullness, bloating, and
nausea
C) Defined as predominant
epigastric pain present for ≥4
wk, with or without heartburn
D) All the above
Answer
• D) All the above
A 45-year-old man presents with complaints of heartburn
often accompanied by a bitter taste in the back of his
throat. These symptoms have been present for several
months and seem to have gotten worse since starting a
high-stress job and gaining weight. You suspect that this
patient has gastroesophageal reflux disease (GERD). All
of the following factors can worsen symptoms of GERD
EXCEPT:
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A:High protein intake
B:Smoking
C:Consumption of decaffeinated coffee
D:Consumption of carbonated beverages
E:Use of a phosphodiesterase inhibitor such
as sildenafil (Viagra®) for erectile
dysfunction
Answer
• A:High protein intake
Alarm features of GERD symptoms that should
lead to endoscopic evaluation in from 1 to 10
days, depending upon the patient?s state of
illness, include all of the following EXCEPT:
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A:Anemia
B:Acute onset dysphagia
C:Melena
D:Involuntary weight loss greater than 5
percent of baseline weight
• E:Age 50 years or older
Answer
• E:Age 50 years or older
Factors Associated with Decreased
Lower Esophageal Sphincter Tone
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Factor
Examples
Dietary supplements
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Arginine via the nitric oxide system
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Carminitive herbs such as peppermint (Mentha xpiperita), spearmint (Mentha spicat)a and other mint family (Lamiaceae) plants
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Essential oils (volatile, scented plant oils in high doses)
Foods/beverages
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Alcohol
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Chocolate (probably via themethylxanthines)
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Coffee (caffeinated more than decaffeinated)
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Cow’s milk
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Fat
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Orange juice & other citrus juices
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Spicy foods
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Tea
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Tomato juice
Lifestyle
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Smoking
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Stress
Medications
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Aminophylline (theophylline)
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Anticholinergics
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Beta-adrenergics
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Calcium channel blockers
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Nitrates
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Phosphodiesteraseinhibitors including sildenafil(Viagra®), vardenafil(Levitra®), tadalafil(Cialis®)
Physiologic, via stomach dilatation
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Post-prandial
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Gastric stasis
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Pyloric obstruction
Trauma/irritation/miscellaneous
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Acid hypersecretion
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Esophagitis
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Scleroderma-like diseases
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Surgical damage
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Gastroesophageal Reflux Disease
Gastroesophageal reflux disease (GERD) is caused by the reflux of acidic stomach contents (refluxate) passing into the esophagus, resulting in symptoms of heartburn,
regurgitation and/or dysphagia. GERD is common. It is estimated that 15 percent of people in the United Stateshave heartburn or regurgitation at least once a week and 7 percent
of people suffer from symptoms daily.
One of the main mechanisms that normally prevents refluxate from entering the esophagus is the lower esophageal sphincter (LES). The LES normally exists in a contracted
state, but it will relax during the swallow sequence to let material into the stomach. The LES also relaxes to vent swallowed air and to allow retrograde expulsion of material from
the stomach. Many substances decrease LES tone and can lead to the development of GERD or the exacerbation of preexisting GERD. These include dietary supplements,
medications, trauma and smoking. (See Table.) The LES may relax with stomach distention, so some experts recommend not overeating or overconsuming fluids with meals to
avoidGERD exacerbation via this mechanism.
Research has been done to examine the specific effects of coffee and other beverages on GERD. For example, coffee (instant coffee, decaffeinated coffee, ground coffee)
decreases LES for up to 90 minutes after ingestion. Caffeinated coffee seems to cause more gastric acid production, resulting in decreased LES tone with a more acidicrefluxate.
Caffeine itself has some ability to decrease LES tone. High protein intake is not associated with GERD.
People report that stress worsens GERD symptoms, a fact that has supported in clinical trials. For example, stress increases GERD symptom reports, without necessarily being
correlated to objective physiological changes such as increased esophageal acid exposure or duration of acid exposure in the esophagus. This phenomenon occurs especially in
people with high levels of anxiety.
Elevating the head of the bed may help decrease GERD symptoms. This should be done by using 4- to 6-inch blocks under the bedposts at the head of the bed rather than using
extra pillows. Extra pillows can compress the abdomen and increase intra-abdominal pressure, exacerbating GERD symptoms.
The mainstay of initial GERD treatment is pharmacologic with histamine type-2 receptor antagonists and proton pump inhibitors. Often, step-down therapy is recommended, so
proton pump inhibitor therapy for 8 weeks is the first choice of treatment in many GERD guidelines. Starting doses include
Esomeprazole (Nexium®) – 40 mg daily
Lansoprazole (Prevacid®) – 30 mg daily
Omeprazole (generic, Prilosec®) – 20 mg daily
Pantoprazole (Protonix) – 40 mg daily
Rabeprazole (Aciphex®) – 20 mg daily
Patients with GERD should be tested for H. pylori infection and treated if positive. Patients who fail to respond to proton pump inhibitor therapy and those who are over the age
of 50 years at the onset of symptoms should be referred for nonurgent endoscopic evaluation. Patients withGERD and alarm symptoms should be referred
for endoscopicevaluation on a more urgent basis (SOR C; Ref. 6). Alarm symptoms and timeframes for endoscopy (in parentheses) are:
Anemia (7-10 days)
Acute onset dysphagia (within 1 day)
Hematemesis (within 1 day if ill-appearing)
Melena (within one day if ill-appearing)
Persistent vomiting (7-10 days)
Involuntary weight loss >5 percent (7-10 days)
Lifestyle modifications, such as smoking cessation and stress reduction, should be recommended, but there is little evidence that these interventions are helpful
(SOR C; Ref. 8).
Selected references:
1. Behrman RE, Kliegman RM, Jenson HB. Nelson Textbook of Pediatrics. 17th ed.Philadelphia: WB Saunders Co., 2004.
2. Bradley LA, Richter JE, Pulliam TJ, et al. The relationship between stress and symptoms of gastroesophageal reflux: the influence of psychological factors. Am
JGastroenterol 1993; 88:11-19.
3. Dennish GW, Castell DO. Caffeine and the lower esophageal sphincter. Am J DigDis 1972; 17:993-996.
4. Feldman M, Barnett C. Relationships between the acidity and osmolality of popular beverages and reported postprandial heartburn. Gastroenterol 1995; 108:125-131.
5. Goyal RK. Diseases of the esophagus. In: Kasper DL, Braunwald E, Fauci AS, et al., eds, Harrison’s Principles of Internal Medicine. New York: McGraw-Hill, 2005.
6. Institute for Clinical Systems Improvement (ICSI). Initial management of dyspepsia and
GERD. http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=9658&nbr=005174&string=GERD Accessed March 2008
7. MacDonald-Haile J, Bradley LA, Bailey MA, et al. Relaxation training reduces symptom reports and acid exposure in patients with gastroesophageal reflux
disease. Gastroenterol 1994; 107:61-69.
8. University of Michigan Health System. Gastroesophageal reflux disease
A 30-year-old woman presents to your office with a complaint of
intermittent abdominal discomfort and bloating as well as recurrent
bouts of diarrhea. This has been going on for the last 6 months and
more than 50 percent of days in a week. She states that the onset of
the pain is associated with the diarrhea and that she gets relief of the
pain when she defecates. You consider the diagnosis of irritable bowel
syndrome (IBS). Which of the following should be routinely ordered
or performed on patients in whom the diagnosis of irritable bowel
syndrome is being entertained?
• A:Colonoscopy
• B:Complete blood count and fecal occult
blood
• C:Stool cultures
• D:Sedimentation rate
• E:Serum chemistries
Answer
• B:Complete blood count and fecal occult
blood
Which of the following
statements is TRUE regarding
the treatment of irritable bowel
syndrome?
• A:Anxiolytic agents have been shown to be
helpful.
• B:Alosetron (Lotronex®) is useful for
constipation-predominant IBS.
• C:Lubiprostone (Amitiza®) is useful only in
women with constipation-predominant IBS.
• D:Dietary changes are generally ineffective.
• E:Interventions such as acupuncture and
psychotherapy are ineffective.
Answer
• C:Lubiprostone (Amitiza®) is useful only in
women with constipation-predominant IBS.
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Irritable Bowel Syndrome
Irritable bowel syndrome (IBS) is the most common functional disorder of the gastrointestinal tract and affects 10-15 percent of
the U.S.population. Although the exact pathophysiology of the disease is uncertain, various etiologies have been proposed. IBS has been
shown to have a familial clustering, suggesting a genetic basis. Ten percent of patients with IBS have a flare-up after a gastrointestinal
infection. Support for a neurologic basis comes from studies showing increase activation of pain signaling areas in the brain on magnetic
resonance imaging (MRI) or positron emission tomography (PET). Other possible etiologies include gut hypersensitivity, small-bowel
bacterial overgrowth, altered gastrointestinal motility, dietary intolerance, stress and other psychological factors. Although some patients with
IBS may have an ongoing low-grade inflammatory state evidenced by an increase number of mast cells in the colon and an increase in the
number of lymphocytes, an autoimmune component has not been proposed.
Traditionally, the diagnosis of IBS has been one of exclusion. The diagnosis is suggested in the absence of red-flag signs and symptoms that
may suggest other serious processes. The American Gastroenterological Association states that a medical history and physical
examination, and certain routine studies, are recommended to assess the presence of “alarm signs” or “red flags” (fever, weight loss,
blood in stools, anemia, abnormal physical findings or blood studies, family history of inflammatorybowel disorders or cancer) that
might require more extensive evaluation. For screening purposes, a stool Hemoccult and complete blood count are recommended
(SOR C; Ref. 1). Other testing (e.g., sedimentation rate, stool cultures, serum chemistries) should be ordered based on symptom pattern.
Colonoscopy is recommended for patients >50 years of age. Typical symptoms of IBS are abdominal bloating, abnormal stool frequency and
form (diarrhea and/or constipation) and mucus in the stool.
The revised Rome III criteria allow physicians to make a provisional diagnosis of IBS. The criteria include recurrent abdominal discomfort at
least 3 days per month during the previous 3 months and 2 of the following 3 features:
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Abdominal discomfort is relieved with defecation.
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Onset of the discomfort is associated with a change in frequency of stool.
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Onset of the discomfort is associated with a change in form (appearance) of stool.
Treatment for IBS consists of dietary modifications and symptom-oriented medications. Conservative therapy is the goal for managing IBS,
and unnecessary surgery should be avoided. Patients should be reassured about this disorder and relaxation training and stress management
considered. The American Gastroenterological Association states that cognitive-behavioral treatment, dynamic (interpersonal)
psychotherapy, hypnosis and stress management/relaxation seem to be effective in reducing abdominal pain and diarrhea (but not
constipation), and also reduce anxiety and other psychological symptoms (SOR C; Ref. 1).
IBS is often classified based on the symptom complex – constipation-predominant, diarrhea-predominant and pain-predominant. Patients with
predominantly constipation may benefit from supplemental fiber in their diet. Patients should be encouraged not to put off the urge to
defecate. Polyethylene glycol and lubiprostone (Amitiza®) may be used for persistent constipation. Patients with diarrhea-predominant IBS
should try dietary changes such as elimination of lactose or caffeine and avoiding artificial sweeteners and high-fat foods. Lactose-intolerant
patients may need to limit their milk consumption. Medications for diarrhea include loperamide, alosetron (Lotronex®) or
a tricyclicantidepressant. Abdominal pain may be relieved with peppermint oil, antispasmodic medications, low-dose tricyclic antidepressants
or selective serotonin reuptake inhibitors (SSRIs). Patients with abdominal bloating should avoid high-fiber diets because the fiber aggravates
the gas. They should also eat more slowly, avoid chewing gum and avoid smoking to prevent excessive air swallowing. Probiotic therapy may
decrease abdominal bloating. Medications that can be used for moderate to severe IBS are shown in the Table. Tegaserod (generic,Zelnorm®)
was indicated for patients with constipation-predominant IBS but was removed from the market in April 2007 because of increased risk of
serious cardiovascular events. Anxiolytics are generally not recommended unless the patient has a comorbid anxiety disorder.
Pharmacologic Treatment of Irritable
Bowel Syndrome
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Medication Type
Medication
Dose
Comments
Antispasmodics
Dicyclomine(generic,Bentyl®)
20 mg 4 times daily
Anticholinergicadverse effects
Hyoscyamine(generic,Levsin®)
0.125-0.25 mg every 4 hours or 0.375-0.75 mg sustained release twice daily
Antidiarrheal
Loperamide(generic, Imodium®)
4-8 mg total daily dose
Helps diarrhea but not other symptoms
Antidepressants
Tricyclics(e.g.,amitriptyline,nortriptyline,imipramine)
Doses lower than those used for depression
Anticholinergicadverse effects (current research investigating efficacy ofSSRIs)
Chloride channel activator
Lubiprostone(Amitiza®)
24 mcg taken twice daily with food
For treatment of constipation; no drug interactions
5-hydroxytryptamine 3 receptor antagonist
Alosetron(Lotronex®)
0.5-1 mg twice daily;
available only through prescribing program
Use in diarrhea-predominant IBS women; risk of ischemic colitis
The classic signs and symptoms
of celiac disease include which
of the following?
Iron-deficiency anemia
Diarrhea
Weight loss
Abdominal pain
A) 1,3
B) 2,4
C) 1,2,3
D) 1,2,3,4
Answer
1. Iron-deficiency anemia
2. Diarrhea
3. Weight loss
In the patient with
dyspepsia, alarm symptoms
or factors that warrant early
referral to endoscopy include
all the following, except:
A) Significant unanticipated
weight loss
B) Difficulty swallowing
C) Bleeding or anemia
D) Age <45 yr
Answer
• D) Age <45 yr
Which of the following drugs should the
patient discontinue 2 wk before the stool
antigen test for Helicobacter pylori?
Proton pump inhibitors
Antibiotics
Bismuth
Nonsteroidal anti-inflammatory drugs
A) 1,3
B) 2,4
C) 1,2,3
D) 1,2,3,4
Answer
1. Proton pump inhibitors
2. Antibiotics
3. Bismuth
Dyspepsia that is bloatinglike in character should be
treated with
a(n)_______agent, while
dyspepsia that is ulcer-like
should be treated with a(n)
_______ agent.
A) Antisecretory; promotility
B) Promotility; antisecretory
Answer
• B) Promotility; antisecretory
According to the United
States Preventive Services
Task Force guidelines for
CRC screening, routine
colon cancer screening
_______ recommended
for individuals 76 to 85 yr
of age.
A) Is
B) Is not
Answer
• B) Is not
All the following statements
about fecal immunochemical
testing are true, except:
A) Less sensitive than fecal
occult blood testing (FOBT)
B) Detects human globin
C) No dietary restrictions
required
D) Less specific than FOBT
Answer
• A) Less sensitive than fecal occult
blood testing (FOBT)
How common is celiac disease?
What are the symptoms?
What tests must you order to
make the diagnosis?
What is the final test before you
put them on a gluten free diet for
the rest of their life?
Answer
• 1 in 125 people
• One in 10 has all the classic symptoms,
anemia, diarrhea and weight loss
• serum tissue transglutaminase antibody
and IgA level; 20% of individuals with
celiac disease do not produce IgA and
antiendomysial antibody
• Duodenal biopsies
Dyspepsia
• “bad digestion”; definition—upper abdominal pain not
related to colon function
• may include early satiety
• fullness,
• Bloating
• nausea (component of many disorders, including
• chronic headaches)
• defined by Talley as predominant epigastric pain
present for 4 wk, with or without heartburn
• heartburn defined as chest burning with gross
regurgitation that can include dyspepsia; not 2
separate diseases, but consider more prominent
symptom
• affects 26% to 41% of citizens in United States;
• 5% of primary care visits
Uninvestigated dyspepsia
• upper abdominal pain, as described, in which no
investigation (invasive or noninvasive) previously
• Performed
• causes—irritable bowel syndrome (IBS)
• Nonulcer dyspepsia (NUD), or functional dyspepsia
• ulcer disease
• gastroesophageal reflux disease (GERD; often has
dyspeptic component);
• carbohydrate malabsorption
• gallstones (foregut organ)
• chronic pancreatitis
• malignancy (eg, pancreatic cancer);
• Ischemia
• systemic diseases (eg, amyloidosis, sarcoidosis)
Medications causing dyspepsia
• top 2 aspirin and nonsteroidal anti-inflammatory
drugs (NSAIDs)
• both most common cause of non-Helicobacter pylori,
non-aspirin/non-NSAID ulcers (due to nonreporting of
medication use by patients);
• others include angiotensin- converting enzyme (ACE)
inhibitors
• Antibiotics
• colchicine,
• Estrogens
• ethanol (causes diarrhea)
• Gemfibrozil
• steroids,
• Iron
• niacin
Gas producing foods
• everyone has carbohydrate intolerance
it is the human condition.
• (no human perfectly digests
carbohydrates), it keeps us humble
• fructose with glucose (eg, apples)
• fructans (eg, onions, leeks, watermelon)
• breads and pasta
• sorbitol (stone fruits eg. nectarines and
peaches)
• raffinose (eg, legumes, cabbage)
Lactose deficiency
• clinically common; low threshold
• lactose in meal easier to absorb
• diagnosis—lactose tolerance test or breath test; simpler test to
have patient drink 3 glasses of milk without food
• treatment—lactose avoidance or lactase supplement
• yogurt well-tolerated; most people, regardless of lactase state
• tolerate one glass of milk daily without problems, no matter what
is the deficiency
• People who produce lactase enzyme “genetic mutants”
(normally stop producing lactase at age of weaning)
• Northern Europeans have no lactase deficiency
• Asian-Americans are lactase-deficient
• Lactaid dietary supplements contain the natural lactase enzyme
that is lacking. Take one tablet with the first bite of dairy and
you can enjoy the food without worrying about discomfort. It
comes in fast act chewables and caplets.
Celiac Disease
• occurs in 1 in 125 people
• >1 million Americans affected (>50% are women)
• only 90,000 exhibit classic signs and symptoms,
including iron-deficiency anemia, diarrhea, and
weight loss
• screening—serum tissue transglutaminase antibody
and IgA level
• 20% of individuals with celiac disease do not produce
IgA
• diagnosis—minimum of 6 biopsies from duodenum
(>90% accurate)
• Can’t always diagnose with red flags
• unable to distinguish celiac disease from IBS by
history
Helicobacter pylori causes
pathogenic changes to acid
production by inducing
dysregulation of _______
production.
(A) Gastrin (C) Tumor Necrosis
Factor (TNF)(B) Somatostatin (D) CagA
protein
Answer
• (B) Somatostatin
In Western countries, which
gastritis distribution is typically
associated with H pylori
infection?
(A) Antral-predominant (B)
Corpus-predominant (C)
Atrophic
Answer
• (A) Antral-predominant
Treating corpus-predominant
gastritis patients for H pylori may
worsen or even induce
gastroesophageal reflux
disease (GERD).
(A) True (B) False
Answer
• (A) True
Which factor in a patient’s
background is the most
significant predictor of H pylori
infection?
(A) Age (C) Use of nonsteroidal
anit-infammatory drugs
(B) GERD (D) Country of origin
Answer
• (D) Country of origin
Resistance to which of the
following antibiotics is
associated with 90% failure rates
when prescribing standard
“triple therapy” to eradicate H
pylori?
(A) Metronidazole (B)
Amoxicillin (C) Clarithromycin
(D) Tinidazole
Answer
• (C) Clarithromycin
Helicobacter pylori timeline:
• H pylori prevalence currently decreasing
• in United States, with resulting dramatic changes in disease
management
• 1982—first cultured accidentally
• Initial attempts to publish rejected by medical community because
orthodoxy convinced ulcers acidogenic and bacteria
• could not survive stomach
• 1984—first paper published; Marshall ingested H pylori and
successfully validated Koch’s postulates
• 1988—first randomized controlled trial treating ulcers as infectious
• 1994—National Institutes of Health (NIH) consensus conference
concluded gastric ulcers share infectious etiology
• H pylori labeled class 1 carcinogen by World Health Organization
(WHO)
• 1997—H pylori genome sequenced
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Pathogenesis
does not invade tissue
incubates beneath gut mucosal layer
produces multiple enzymes and induces development of toxins
provokes strong immune response
systemic immune response allows serologic detection
local immune response affects acid secretion via dysregulation of D cell (produces
somatostatin)
Western populations
typically experience antral-predominant gastritis with somatostatin down-regulation
gastrin upregulation,
increased acid secretion and risk for duodenal ulcer
reduced risk for gastric cancer
Eastern populations
typically develop corpus-predominant gastritis
Somatostatin up-regulation
acid suppression
decreased gastrin, and higher risk for gastric cancer
protected against duodenal ulcer and gastroesophageal reflux disease (GERD)
duodenal ulcers increasingly rare due to widespread use of proton pump inhibitors
(PPIs) and antibiotics
Nonsteroidal anti-inflammatory
drug (NSAID)–induced ulcers:
• until mid 1990s, most ulcers attributed
to H pylori
• NSAIDs currently most common
etiology
• virtually all complicated (bleeding)
ulcers now NSAID-related
GERD and H pylori: distribution of
gastritis determines treatment
• GERD symptom history critical; in patients with preexisting GERD and typical Western antral-predominant
gastritis
• treatment for H pylori results in reduced acid production
and improvement of reflux in those without preexisting
GERD
• new GERD unlikely to develop; in patients with Eastern
corpus-predominant gastritis
• treatment for H pylori increases acid production
• GERD may worsen or develop from latent form
• controversies surrounding treatment of H pylori result
from geographic variations in distribution of gastritis
Functional dyspepsia: dyspepsia
lacks singular etiology
• Functional nonulcer dyspepsia responds
poorly to treatment of H pylori (only 1 in 15
patients improve
• testing dyspeptic individuals for H pylori
recommended only in areas with established
high demographic prevalence
• H pylori infection window ends after age 5
yr
• country of origin predicts risk forH pylori
infection
H pylori and cancer
• Correa cascade —H pylori induces atrophic gastritis,
intestinal metaplasia, dysplasia, and cancer
• progression determined by genetics
• alternative theory
• suggests 1) bone marrow produces premalignant cells
• 2) chronically inflamed tissues induce pluripotent cell
migration
• 3) premalignant cells generate tumors at site of
inflammation
• disrupting migration of premalignant cells may prevent H
pylori–related malignancies
• possible concept can be extrapolated to other cancers
Genetics and gastric cancer
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H pylori strains expressing cagA protein associated with increased risk for gastric
cancers
cagA-negative strains also induce malignancies
Genetics determine cancer susceptibility, especially polymorphisms of inflammatory
mediator genes
eg, interleukin-1 (IL-1
higher in cancer patients than in controls); some relatives of patients with gastric cancer
produce less stomach acid
These individuals susceptible to gastric cancer and express genetic polymorphisms
affecting IL-1 , IL-8, IL-10, and tumor necrosis factor (TNF)-alpha
all associated with increased risk for gastric cancer
distribution of gastritis also relevant
Study data—found early treatment of H pylori may prevent development of gastric
cancer
however, preventive treatment ineffective
once irreversible premalignant intestinal changes (eg, metaplasia, dysplasia) have
occurred
Mucosa-associated lymphoid tissue (MALT) lymphoma: B-cell lymphoma, but
dependent on stimulation of T-cells by H pylori
can be cured with antibiotics, but may require conventional lymphoma therapy when
found outside gastric mucosa
Diagnosis of H pylori
• serology unreliable for diagnosis, but negative
predictive value good
• breath test has improved positive predictive value
• stool antigen testing effective
• Enzymelinked immunosorbent assay (ELISA)
provides excellent sensitivity and specificity
• serology stays positive long after treatment
• PPI therapy alters intestinal microorganism
populations, masking endoscopy results
• only multiple biopsies reliably detect H pylori in
patients who use PPIs
• immunologic staining may improve detection
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Treatment
no ideal treatment of H pylori
significant resistance rates exist among commonly used antibiotics
10% to 11% resistance to clarithromycin
clarithromycin resistance associated with 90% failure rate in standard
PPI-based triple therapy
30% to 70% resistance to metronidazole; can overcome resistance to
metronidazole by increasing dose, but clarithromycin resistance
absolute
Suggested treatment: includes PPI, amoxicillin, and clarithromycin for
14 days (increases compliance)
metronidazole may be substituted for amoxicillin in penicillin-sensitive
patients, but reduces efficacy
bismuth, metronidazole, and tetracycline regimen also used
PPI, amoxicillin, and metronidazole least expensive regimen
useful for patients exhibiting macrolide resistance, but results poorer
overall (50%-60% success rate vs 70% average)
25% to 30% of patients do not respond
Sequential therapy
• involves amoxicillin and PPI twice daily for 5 days;
followed by PPI, clarithromycin, and tinidazole for 5 days
• regimen demonstrates 90% eradication, (>80% with
clarithromycin resistance, vs 10%-15% with triple therapy)
• single-pill dosing with bismuth, metronidazole, and
tetracycline (Pylera) increases compliance
• results comparable to triple therapy (circumvents
clarithromycin resistance)
• Rescue therapies
• prescribed after patient fails 2 previous regimens
• frequently PPI, amoxicillin, and levofloxacin; rifabutin
regimen costly and associated with hematologic side
effects;
• furazolidone (uncommon in United States) available from
compounding pharmacies
Guidelines for diagnosis and treatment of
H pylori (American
College of Gastroenterology [ACG])
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ulcer disease
Past history of ulcer MALT lymphoma
early gastric cancer
Uninvestigated dyspepsia (some populations)
Controversial indications—functional dyspepsia
(endoscopy-negative)
GERD
NSAID use
unexplained iron deficiency anemia
Idiopathic thrombocytopenic purpura (ITP)
populations at high risk for gastric cancer
Definition of dyspepsia
• It consists predominantly of epigastiric pain, early
satiation and postprandial fullness, present for 1
month with or without heartburn (Rome III
Committee)
• It is experienced regularly by 25% to 34% of
Americans and accounts for over 5% of visits to a
primary care provider.
• Patients may describe as indigestion or bloating,
early satiety, nausea and vomiting
• Health care providers have also defined dyspepsia
in different ways and as a result a multitude of
esophageal, gastroduodenal, pancreatic, and
hepatobiliary disorders could underlie the
symptoms
Causes of dyspetic symptoms
• Top 3 causes are ulcers, reflux disease and nonulcer
dyspepsia
• Other causes include carbohydrate malabsorption,
gallstones, chronic pancreatitis, malignancies, ischemic
changes and other systemic diseases
• Consider celiac disease which affects 1 in 150 Americans
• Duodenogastric reflux, hypervigilance and somatic
manifestation of psychiatric disease
• Medication intolerance, abdominal pain is a classic side
effect of proton pump inhibitors and many other
medication may cause dyspepsia. Review all medications
with the patient, including nonprescription agents
• The most common cause of dyspepsia is functional
(idiopathic) also referred to as nonulcer dyspepsia
Pathophysiology of nonulcer
dyspepsia
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Impaired gastric accommodation
Visceral hypersensitivity
Delayed gastric emptying
Helicobacter pylori infection
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Refer for upper endoscopy if the
following alarm symptoms are
present
Age greater than 45 years old
Weight loss of greater than 10%
Bleeding
Increasing dysphagia
Severe vomiting or early satiety
History of ulcers or esphagogastric cancer
Family history of GI cancer
Abdominal mass of lymphadenopathy detected on
physical examination
• Unexplained iron deficiency anemia
Drugs that can cause dyspepsia
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Calcium channel blockers
Methylxanthines
Alendronate
Orlistat
Potassium supplements
Acarbose
Erythromycin
Metronidazole
Test and treat or treat then test?
• Few randomized, controlled trails have compared
strategies of empiric antisecretory therapy versus
immediate investigation. Nevertheless, the limited data
support the conclusion that antisecretory therapy compared
with investigative strategies neither saves money nor
improves quality of life in patients with dyspepsia. The
empiric treatment strategy was associated with higher
costs, primarily because of higher number of sick-leave
days and medication costs.
• In young patients without alarm symptoms some studies
have suggested that First perform a 13C urea breath test or
a stool antigen test for H phlori infection, if positive, treat
with H phlori eradication for 2 months, then reevaluate
• Alternatively, try PPI at least twice daily for 4 to 8 wk
• PPI trail should be first choice if the community H Pylori
prevalence is less than 10%
Test and treat or treat then test?
• One of the largest trails to address this issue included 500
patients with dyspepsia with a median age of 45 years who
were randomly assigned to a test and treat strategy or
prompt endoscopy.
• After on year of follow-up there was no significant
difference in symptoms, quality of life, number of sickleave days, visits to general practitioners, or hospital
admission between the groups
• There were 60% fewer endoscopies performed in the testand –treat group
• A higher number of patients were dissatisfied with their
management in the test-and-treat group compared to
endoscopy (12% versus 4%).
H Pylori as a cause of dyspepsia
• Results of 2 studies contradictory
• American College of Gastroenterology
recommends H pylori testing for
uninvestigated dyspepsia on a case-by-case
basis
Testing for H phlori
• The rate of H phlori infection is decreasing in western
society
• This decreases the effectiveness of tests, leading to more
false negatives and more false positives in low-prevalence
areas such as the US
• Antibodies persist, so serologic testing is not
recommended in low-prevalence areas.
• Urea breath test has a high sensitivity and specificity,
although it has a high rate of false-negative results if the
patient is already on acid suppression, on antibiotics for the
past 2 months, or is taking PPIs or bismuth-based
medication
• Stool antigen test has a sensitivity and specificity similar to
those of the urea breath test and the drawbacks are similar
• Rapid test is now available with results in 5 minutes
Endoscopy
• It is the gold-standard
• The diagnostic yield of endoscopy increases
with age
• Early endoscopy increases the chance of
finding a curable rather than incurable
gastric cancer
Major Society Recommendations
• European Helicobacter Pylori Study Group
consensus statement regarding management of
patients with dyspepsia as developed from a
multinational European meeting in March 2005
• They recommended a test and treat strategy in
adults less than 45 years of age who present with
persistent dyspepsia
• They noted that the age cutoff may vary between
countries, depending upon the prevalence of
gastric cancer
• In areas of low H. Pylori prevalence (less than
20%), empirical PPI treatment or a test and treat
strategy were considered to be equivalent
American Gastroenterological
Association recommendations
• Patients 55 years of age or younger without alarm features should
receive a test and treat approach followed by acid suppression.
• If symptoms remain H. Pylori testing should be performed using a 13C
urea breath test or stool antigen test
• Those who are H. Pylori negative should be given an empirical trial of
a PPI for four to eight weeks
• Empirical PPI therapy is the most cost-effective approach in
populations with a prevalence of H. Pylori infection of 10% or less
• Young patients who respond to H. Pylori test and treat or PPR therapy
can be managed without further investigation since endoscopy usually
adds little even in those who continue to have upper gastrointestinal
symptoms but do not have alarm symptoms
• The age of 55 years and older and those with alarm symptoms was
based mainly on expert opinion due to the generally low risk of
malignancy in most US populations
• The age cutoff of 45 to 50 years may be more appropriate for US
patients of Asian, Hispanic, or Afro-Caribbean extraction.
Managing dyspepsia
• Determine whether the pain is similar to ulcer pain
or mainly bloating sensation
• Epigastric pain syndrome – ulcer like pain,
discontinue nonsteroidal anti-inflammatory drugs
and try antisecretory agents like PPIs
• Other agents Metoclopramide which has a high
likelihood of side effects including Parkinsons
symptoms, Cisapride which is essentially
unavailable and low-dose tricyclic antidepressants,
selective serotonin reuptake inhibitors,
psychotherapy and hypnosis
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Dietary causes of bloating and
dyspepsia
Caffeine
Fatty foods in excess
Fruit
Sorbital
Fructose
Lactose
Beans
Raw cabbage
Broccoli
Cauliflower
Carbonated beverages
Some spices
Have a patient keep a dietary history for I week
Complementary remedies
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Peppermeint oil
Caraway oil
Artichoke leaf extract
Capsaicin
Celandine
STW (lberogast) is a combination of 9
extracts, the company supported trails
support use for functional dyspepsia
Diagnosis
• Comprehensive evaluations reveal no identifiable
causes of dyspepsia in 30 to 60% of cases
• History alone is insufficient for distinguishing
ulcer form nonulcer dyspepsia
• Animal studies suggest acidinduced gastric
damage makes normal distention painful, even
after lesions heal
• For humans this may result in dyspepsia
• Some people genetically more susceptible to
unexplained functional dyspepsia
Which of the following
conditions is not one of the top 3
causes of dyspepia?
a.
b.
c.
d.
Ulcers
Gastroesophageal Reflux Disease
Psychosomatic Illness
Nonulcer dyspepsia
ANSWER
c. Psychosomatic illness
A patient complains of classic dyspeptic
symptoms but has not undergone any test.
You decide to order an endoscopy when you
learn that he:
a. Is 40 years of age
b. Has no personal or family history of
gastrointestinal cancer
c. Drinks a six-pack of cola daily
d. Has lost more than 10% of his body weight
within the last month
ANSWER
d. Has lost more than 10% of his body weight
within the last month.
PPIs can cause Abdominal Pain?
a. True
b. False
ANSWER
a. True
Urea breath testing for
Helicobacter Pylori is becoming
less reliable in the western world
because?
a. The overall prevalence of H Pylori
infection is decreasing
b. H Pylori is endemic in this region
c. The isotope used in the test is unstable
d. Newer strains of H Pylori use less urea
than older strains
ANSWER
a. The overall prevalence of H Pylori infection
is decreasing
In at least _____% of patients
with dyspepsia, the cause is never
identified
a.
b.
c.
d.
10%
20%
30%
40%
ANSWER
c. 30%
The cause of dyspepsia is never identified in
30 to 60% of patients
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WHEN TO TEST
There are a number of clinical circumstances in which testing for H. pylori is
considered. Recommendations for diagnostic testing for H. pylori were first
proposed by the National Institutes of Health (NIH) in 1994 [1]. More recent
guidelines were published in 2006 by the European Helicobacter Study Group
(EHSG) [2] and in 2007 by the American College of Gastroenterology (ACG)
[3].
ACG recommendations — The ACG guidelines made the following
conclusions [3]:
Testing for H. pylori should be performed only if the clinician plans to offer
treatment for positive results.
Testing is indicated in patients with active peptic ulcer disease, a past history
of documented peptic ulcer or gastric MALT lymphoma.
The test-and-treat strategy for H. pylori (ie, test and treat if positive) is a
proven management strategy for patients with uninvestigated dyspepsia who
are under the age of 55 years and have no "alarm features" (bleeding, anemia,
early satiety, unexplained weight loss, progressive dysphagia, odynophagia,
recurrent vomiting, family history of GI cancer, previous esophagogastric
malignancy).
Deciding which test to use in which situation relies heavily upon whether a
patient requires evaluation with upper endoscopy and an understanding of the
Uncomplicated duodenal ulcers and gastric ulcers
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Uncomplicated duodenal ulcers — H. pylori is present in the majority of
patients with uncomplicated duodenal ulcers, especially if nonsteroidal
antiinflammatory drugs are excluded [1]. As a result, it has been argued that no
diagnostic method is cost-effective in such patients, and that treatment should
be empiric [4]. However, H. pylori infection is absent in up to 27 percent of
patients with endoscopically proven duodenal ulcers [3]. Such patients appear
to have a significantly worse outcome, especially when treated empirically for
infection [5]. (See "Helicobacter pylori-negative peptic ulcer disease").
Thus, confirmation of infection should be obtained. The diagnosis can be
established by a biopsy urease test if the patient is not taking a proton pump
inhibitor or other medication that could interfere with the test (see "Biopsy
urease testing" below).
Uncomplicated gastric ulcer — H. pylori infection is present in the majority
of uncomplicated gastric ulcers [6]. However, H. pylori negative gastric ulcers
have been increasingly recognized. The surreptitious or unrecognized use of
nonsteroidal antiinflammatory drugs may account for some of these cases.
(See "Helicobacter pylori-negative peptic ulcer disease").
Testing for H. pylori infection should be performed before antibiotic
treatment. One approach is to obtain biopsies from the ulcer's edge and base to
exclude gastric cancer plus at least two separate sites in the gastric mucosa
distant from the ulcer to identify H. pylori organisms. Even if the biopsy does
not indicate malignancy, confirmation of gastric ulcer healing is recommended
in most instances within two to three months.
CONFIRMATION OF ERADICATION
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Confirmation of eradication should be strongly considered because of the availability of accurate,
relatively inexpensive noninvasive tests (stool and breath tests). Confirmation of eradication has been
recommended by a European consensus panel [2]. A 2007 guideline from the American College of
Gastroenterology recommends confirming eradication in the following settings [3]:
Any patient with an H. pylori-associated ulcer
Individuals with persistent dyspeptic symptoms despite the test-and-treat strategy
Those with H. pylori-associated MALT lymphoma
Individuals who have undergone resection of early gastric cancer
The above recommendations are based largely on expert consensus agreement.
Urea breath testing performed at least four weeks after treatment has been promoted as the test of
choice to confirm eradication of infection [2]. Stool antigen testing is a more widely available
alternative, but it may be less accurate [57]. Until further data are available, the stool antigen test
should not be performed sooner than four to six weeks after completion of treatment because of both
false-positive and false-negative results in this time period [55,57].
Recent antibiotics taken for reasons other than H. pylori eradication or recent treatment
with bismuth or PPIs can affect test results. Antibiotics and bismuth should be discontinued for at
least four weeks and PPIs at least one week if possible prior to testing done to confirm H. pylori cure
(with urea breath test, stool antigen testing, or endoscopic testing) to reduce the chance of falsenegative results.
Endoscopy with biopsy for culture can be performed when antibiotic resistance is suspected. A
biopsy obtained for histopathology only is appropriate if urea breath testing or stool antigen testing is
not feasible or during follow-up of complicated ulcer disease. Serologic testing is not useful for
follow-up since many patients continue to have antibodies for months or even years after eradication
therapy [67].
Functional dyspepsia
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DEFINITION — An international committee of clinical investigators
developed the following revised definition (Rome III criteria) of functional
dyspepsia for research purposes, which can also be applied to clinical practice
[1]:
One or more of:
Bothersome postprandial fullness
Early satiation
Epigastric pain
Epigastric burning
AND
No evidence of structural disease (including at upper endoscopy) that is likely
to explain the symptoms.
These criteria should be fulfilled for the last three months with symptom onset
at least six months before diagnosis. Two subcategories (postprandial distress
syndrome and epigastric pain syndrome) were also recognized but their main
value lies currently in research.
Dyspepsia has been classified according to the characteristics of symptoms
that predominate. However, such classification systems do not reliably
correlate with underlying pathophysiologic mechanisms
PATHOPHYSIOLOGY
—
• The pathophysiology of functional
dyspepsia is unclear. Research has focused
upon the following factors:
• Gastric motor function
• Visceral sensitivity
• Helicobacter pylori infection
• Psychosocial factors
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Gastric motor function
Gastric motor function — Normal gastrointestinal motor function is a complex series
of events that requires coordination of the sympathetic and parasympathetic nervous
systems, neurons within the stomach and intestine, and the smooth muscle cells of the
gut. Abnormalities of this process can lead to a delay in gastric emptying
(gastroparesis), a disorder that is characterized by complaints of nausea, vomiting, early
or easy satiety, bloating, and weight loss. (See "Etiology and diagnosis of delayed
gastric emptying").
Delayed gastric emptying has been found in approximately 30 percent of patients
complaining of dyspepsia [4-6]; however, there is generally a poor correlation between
these entities. Antral hypomotility has been found in a similar proportion of patients, but
its relationship to symptoms is also uncertain. Up to 10 percent of patients have fast
gastric emptying, which may also be associated with dyspepsia.
The relationship between gastric motor function and gastric volumes may be important.
A study of 57 adults suggested that symptoms were associated with low fasting gastric
volume and faster gastric emptying [7].
Gastric compliance is lower in patients with functional dyspepsia than in healthy
controls [8,9]. In one study, for example, postprandial gastric accommodation was
evaluated in 40 patients with functional dyspepsia and 35 healthy controls [9]. Impaired
gastric accommodation was found in 40 percent of patients with functional dyspepsia
(compared to the lower range observed in controls), and was associated with early
satiety and weight loss. Treatment with sumatriptan (a 5-hydroxytryptamine agonist that
causes fundus relaxation) restored gastric accommodation and improved meal-induced
satiety.
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Visceral sensitivity
Enhanced visceral sensitivity or visceral hyperalgesia refers to a lowered threshold for
induction of pain by gastric distension in the presence of normal gastric compliance.
Visceral hypersensitivity has been consistently demonstrated in patients with functional
dyspepsia [10-12]. In a representative study, for example, the sensorial responses (on a 0
to 10 perception score) and the gastric tone responses (by electronic barostat) to either
gastric accommodation or to cold stress were measured in 20 patients with functional
dyspepsia and 20 healthy controls [10]. The mechanical accommodation of the stomach
to gastric distention (compliance) was similar in patients and controls (52 versus 57
mL/mmHg). However, isobaric gastric distention elicited more upper abdominal
discomfort in the patients with dyspepsia (perception scores 4.7 versus 1.1). Similar
findings were noted in another report in which reduced perceptual thresholds or altered
pain referral were found in 20 of 23 patients (87 percent) with functional dyspepsia
compared to only 2 of 10 patients (20 percent) with organic causes of dyspepsia [11].
Patients with dyspepsia are also more sensitive to acid infusion into the duodenal bulb
(which produced nausea and fewer duodenal pressure waves) compared to controls [12].
Visceral hypersensitivity, which has also been proposed as an etiologic factor in irritable
bowel syndrome, appears to occur independent of delayed gastric emptying [13]. (See
"Pathophysiology of irritable bowel syndrome"). In contrast, somatic sensitivity (as
measured by transcutaneous electrical stimulation of the hand) is normal in these
patients [14].
Both mechanoreceptor dysfunction (peripheral mechanism) and aberrant processing of
afferent input in the spinal cord or brain (central mechanism) may play a role in the
pathophysiology of visceral hypersensitivity. The latter mechanism is supported by the
observation that sympathetic autonomic activity enhances the perception of gut
distension in normal subjects
Helicobacter pylori infection —
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Helicobacter pylori infection — Although a possible role for H. pylori infection in functional dyspepsia is suggested by several
potential pathogenic mechanisms, a clear association among these factors, H. pylori, and functional dyspepsia has not been
established.
H. pylori is a well known cause of chronic active gastritis. However, gastritis is probably not the cause of symptoms in most
patients with functional dyspepsia. A consistent link between findings on endoscopy and dyspepsia has not been found [16].
H. pylori may cause altered smooth muscle dysfunction due to the induction of an inflammatory response or by the initiation of
an antibody response [17]. (See "Pathophysiology of and immune response to Helicobacter pylori infection"). However, most
studies have not found an association between H. pylori and abnormal gastric motor function in patients with functional
dyspepsia. In one report, for example, the gastric function of 27 patients with functional dyspepsia and H. pylori infection was
compared to that of 38 uninfected patients with functional dyspepsia [18]. The gastric emptying time was similar in both groups.
The inflammatory response induced by H. pylori may lower the discomfort threshold to gastric distension by causing alterations
in the enteric or central nervous system [17]. However, visceral hypersensitivity did not appear to be important in at least one
study which found that H. pylori positive and negative patients with functional dyspepsia had no difference in the perception of
mechanically-induced gastric distension [19].
In addition to these rather unconvincing findings, most studies have not been able to establish a temporal relationship between H.
pylori infection and chronic dyspepsia, nor has a specific symptom complex been linked to H. pylori [17]. Furthermore, multiple
studies have evaluated the benefit of eradicating H. pylori in patients with functional dyspepsia, but results have been conflicting
[20], although in aggregate they suggest a small significant benefit [21]. The results of three trials illustrate the controversy:
In one study, 318 patients with dyspepsia who were H. pylori positive were randomly assigned to antibiotic therapy aimed at
eradicating the infection or to omeprazole without antibiotics for the same duration [22]. After one year of follow-up, dyspepsia
resolved significantly more frequently in patients who received antibiotic therapy (21 versus 7 percent). Resolution was more
common in patients who had had symptoms for five years or less (27 versus 12 percent).
Two similarly designed studies involving 328 and 170 patients, respectively, reached the opposite conclusion [23,24]. At the end
of one year of follow-up, no significant differences in dyspepsia or quality of life were detected between the two groups.
Despite the similar study design, differences in inclusion criteria and outcome measures may have accounted for the discordant
results [25]. A meta-analysis concluded that there was evidence for a small benefit [21]. Thus, at best, only a minority of patients
with functional dyspepsia will benefit from H. pylori eradication. This conclusion was supported by a systematic review of 21
randomized controlled trials, which found that 14 patients needed to be treated to cure one case [26].
Nevertheless, guidelines issued by the American Gastroenterological Association and the American College of Gastroenterology
recommend H. pylori eradication in patients with functional dyspepsia emphasizing a possible short-term benefit (number needed
to treat around 17) and a possible long-term benefit for prevention of gastric cancer
Psychosocial factors
• No unique personality profile has been found in patients with
functional dyspepsia; however, anxiety, somatization, neuroticism, and
depression are increased in this group compared with healthy controls
[4,34]. Higher levels of psychopathology have also been found in
patients with functional dyspepsia compared to those with duodenal
ulcer; the most important factor was multiple somatic complaints [35].
However, the psychological profile and health care seeking behavior in
patients with dyspepsia may vary among different cultures. In a study
of Australian patients with dyspepsia, for example, health care seeking
was related more to symptom severity and duration than to
psychological factors [36].
• There is a link between self-reported childhood abuse and functional
gastrointestinal disorders [37,38]. It has been suggested that functional
dyspepsia is best understood as the result of a complex interaction of
psychosocial and physiological factors
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TREATMENT
Treatment of patients with functional dyspepsia is controversial and often disappointing, a sharp
contrast to the therapy of peptic ulcer disease [40]. The goal is to help patients accept, diminish, and
cope with symptoms rather then eliminate them [40].
Similar to patients with irritable bowel syndrome, the most important aspects of the therapy of
functional dyspepsia include explanation, validation that the symptoms are not imaginary, evaluation
and management of relevant psychosocial factors, and dietary advice. Medications that might
contribute to symptoms (such as NSAIDs) should be substituted or discontinued whenever possible.
(See "Patient information: Abdominal pain (functional dyspepsia) in adults").
Drug therapy, which is based upon the putative pathogenetic mechanisms described above, may help
some patients. Several systematic reviews have summarized treatment trials of pharmacologic
therapy for nonulcer dyspepsia [41-46]. One of the most comprehensive summaries focused on 57
trials comparing a variety of pharmacologic interventions [42]. The following conclusions were
reached:
Prokinetic agents were more effective than placebo (relative risk reduction (RRR) of 50 percent, 95%
CI 30 to 65 percent).
H2 receptor antagonists were more effective than placebo (RRR of 30 percent, 95% CI 4 to 48
percent).
Proton pump inhibitors and bismuth salts were more effective than placebo, but the benefits were of
marginal statistical significance.
There was no statistically significant benefit from antacids, bismuth, or sucralfate.
A limitation of virtually all the treatment trials was their short duration, calling for caution in
accepting the benefits in a disorder characterized by chronicity. Interpretation of drug trials is also
complicated by the heterogeneous nature of the syndrome, the possible dissimilarity of statistical and
clinical significance [47], the possible inclusion of patients with gastroesophageal reflux, which
could respond to prokinetic agents or acid suppression, and the uncertainty that the study patients are
representative of those cared for by primary care physicians (by far the largest group).
ABDOMINAL PAIN DIAGNOSIS
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There are a number of reasons why you can develop symptoms of dyspepsia. Organic (nonfunctional) dyspepsia can cause symptoms that are similar to those of functional dyspepsia, or the
symptoms may be slightly different. A healthcare provider will perform a medical history and
physical examination to narrow the possible list of causes, with special attention to the following:
Is the pain "gnawing" or worsened by hunger?
Is the pain worsened by certain movements or pressure on certain areas of the abdomen?
Do you take medications for pain, such as aspirin, ibuprofen (Advil, Motrin) or naproxen (Aleve)?
Do you have a history of ulcers?
Do you have heartburn in addition to upper abdominal discomfort?
Do you have intense pain in the upper right or middle of the abdomen? Does the pain extend to the
back or between the shoulder blades? Does this happen periodically, along with vomiting, sweating,
or feeling restless?
Have there been changes in your bowel habits (eg, constipation or diarrhea)?
Have you recently unintentionally lost weight, vomited repeatedly, or had difficulty swallowing?
Testing recommendations — The best way to diagnose functional dyspepsia is not clear. The
American Gastroenterological Association suggests the following:
People who are older than 55 or with serious symptoms, such as repeated vomiting, weight loss,
difficulty swallowing, or a low blood count, should have an upper endoscopy procedure. (See
"Patient information: Upper endoscopy").
People who are younger than 55 and who do not have serious symptoms are generally offered
noninvasive testing to detect infection with H. pylori (eg, stool or breath testing). (See "Patient
information: Helicobacter pylori infection and treatment").
If symptoms fail to improve within four to eight weeks or if more serious symptoms develop, further
testing, including upper endoscopy, is usually recommended. Other diagnostic tests may be
recommended in selected cases.
ABDOMINAL PAIN TREATMENT
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Understanding the condition — Being diagnosed with functional dyspepsia may be a relief to some people and a frustration to
others. It is important to understand that symptoms are not imaginary. One or more treatments may be recommended, often in
combination; having realistic expectations of the benefits of treatment may help to reduce frustration. If there are mood problems,
such as anxiety or depression, an evaluation with a mental health specialist (eg, social worker, psychologist, counselor) may be
recommended.
Lifestyle changes — Some people benefit from avoiding fatty foods (which can slow the emptying of the stomach), and eating
small frequent meals. Foods that aggravate symptoms should be avoided, if possible, although eliminating entire food groups is
not recommended. If you have questions about which foods should be avoided, discuss this with a healthcare provider and/or
dietitian.
Medications — Certain medications may help to reduce the symptoms of functional dyspepsia.
Acid reducing medications — Some people benefit from treatment with medications that inhibit or reduce the production of
stomach acid (eg, H2 blockers such as Zantac®, Axid®, or Pepcid® or proton pump inhibitors such as Prilosec®, Nexium®,
Prevacid® AcipHex®, or Protonix®).
H. pylori therapy — Treatment of H. pylori is recommended if an ulcer is diagnosed. (See "Patient information: Helicobacter
pylori infection and treatment").
This treatment may be considered for people who have H. pylori, but who are not known to have an ulcer. However, the benefit
of treating H. pylori in this situation is unclear. At best, a small proportion of people with functional dyspepsia improve following
treatment of H. pylori.
Visceral analgesics — As mentioned previously, some people with dyspepsia are sensitive to enlargement (distension) of the
stomach. Medications that relieve visceral pain are being studied, but are not yet available.
Pain medications — Low doses of an antidepressant medication may be recommended to reduce pain, even if the patient is not
depressed. The dose of TCAs is typically much lower than that used for treating depression. It is believed that these drugs reduce
pain perception when used in low doses, but the exact mechanism of their benefit is unknown.
TCAs commonly used for pain management include amitriptyline,desipramine, and nortriptyline. In the beginning, many people
who take TCAs experience fatigue; this is not always an undesirable side effect since it can help improve sleep when TCAs are
taken in the evening. TCAs are generally started in low doses and increased gradually. Their full effect may not be seen for
weeks to months.
Narcotic pain medications, such as codeine, hydrocodone, oroxycodone, are not usually recommended for long-term relief of
functional dyspepsia because of the risk of side effects (eg, constipation) and the potential risk of becoming addicted.
Complementary and alternative medicine — Several complementary and alternative medicine approaches to functional
dyspepsia have been described. Studies involving herbal and natural products, acupuncture, and homeopathy suggested a benefit
frompeppermint oil and STW5 (a European multi-herbal preparation that includes peppermint and caraway, also known as
Iberogast). However, the quality of the evidence supporting these treatments is generally poor.
More research is needed before these approaches can be routinely recommended.
ABDOMINAL PAIN
PROGNOSIS — Dyspepsia is
typically a relapsing condition. In
studies, 60 to 90 percent of people
continue to have symptoms of
varying degree two to three years
after being diagnosed. However,
most people feel better once their
condition has been diagnosed, and
many will respond to the treatments
discussed above.