PROBLEMS IN THE GI TRACT
| CELIAC DISEASE —Jack A. Di Palma, MD, Professor of Medicine and Director, Division of Gastroenterology, University
of South Alabama College of Medicine, Mobile, Alabama
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| Prevalence: most cases of sprue not diagnosed; should affect ≈1% of population, but clinical prevalence lags; some patients
have classic diarrhea/malabsorption presentation; some patients may have latent or silent sprue and present with
anemia, osteoporosis, dermatitis herpetiformis, recurrent fetal loss, autoimmune disorders (eg, type 1 diabetes,
Sjögren’s syndrome, primary biliary cirrhosis, alopecia areata, thyroid disease, neuropathy, Addison’s disease, vitiligo),
hepatitis B or C
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| Diagnosing sprue: “I think all roads are still coming to biopsy”; in celiac disease, intestine has flat villi, inflammation,
and crypt hypoplasia; can use endoscopic biopsy instead of traditional small bowel biopsy; go to level of ampulla of
Vater; take 4 to 6 samples; use Marsh classification
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 | Serology: most clinicians today use serology; IgG antigliadin antibody (AGA) first used; then discovered IgA connective
tissue autoantibodies (eg, reticulin, endomysial antibodies [EMA], and tissue transglutaminase [tTG]); EMA and
tTG antibodies optimal for diagnosing sprue; tTG has become standard of care (not as specific as EMA but much easier
to perform); tTG can give false-positive results in patients with liver disease, heart failure, rheumatoid arthritis,
psoriatic arthritis, and false-negative results in patients on gluten-free diet, immunosuppressives, or who have seronegative
sprue or selective IgA deficiency; obtain total IgA, EMA, and tTG in patients for whom physician has high index
of suspicion for sprue
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| Endoscopic findings: reduction in duodenal folds; scalloping; mucosal cracks and fissures; most common reliable
finding in sprue is reduction in duodenal folds
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| Hydrogen breath testing: might be superior to serologies, particularly when following patients; reversion to normal
heralds recovery of mucosa
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| Iron deficiency anemia: may see silent or latent sprue (studies show incidence 2.8%-15.0%); if anemia remains unexplained
by colonoscopy and esophagogastroduodenoscopy (EGD), test for celiac sprue
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| Irritable bowel syndrome (IBS): speaker sees at least one of these patients per month; difficult to convince them they
do not have celiac sprue
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| Case: 38-yr-old woman meets Rome II criteria for IBS; has diarrhea-predominant disease; has bloating, fatigue, and
lassitude; feels better on gluten-free diet; EMA and tTG for IgA negative because patient on gluten-free diet; small
bowel biopsy also negative; patient refuses to stop gluten-free diet in order to obtain accurate readings
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| Discussion: HLA typing helpful in this situation; with negative serologies, biopsy, and HLA associations and lower
index of suspicion, patient probably does not have sprue
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| Guidelines for diagnosing sprue: consider sprue as possibility; no single test can definitively diagnose sprue; use IgA-
tTG or IgA-EMA; do not use AGA; perform biopsy; confirm diagnosis with symptom resolution on gluten-free diet;
demonstration of normalized histology no longer required
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| Special situations: obtain IgA antibodies if index of suspicion high; consider causes of false-positive and false-negative
results; HLA-DQ2 and HLA-DQ8 present in 97% of patients with sprue and 30% to 40% of general population, but if
negative, unlikely patient has sprue
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| Refractory sprue: patient not following gluten-free diet; may not be sprue; may have co-condition, eg, overgrowth or
lymphocytic colitis; may have cryptic T cell lymphoma
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| Cryptic T cell lymphoma: intraepithelial lymphocytes and altered immunophenotypes; may progress to enteropathy-associated
T cell lymphoma (EATL); in celiac disease, have CD3, CD8, and T cell antigen receptor (TCR); in refractory
sprue of cryptic T cell lymphoma type, panel different
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| Lymphocytic duodenitis: may be forerunner of sprue; patients have HLA association; 33% have positive serology; many
improve on gluten-free diet; may have some relationship with dermatitis herpetiformis, bone disease, anemia, and IBS
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| Complications: ulcerative jejunoileitis; malignancies (esophageal, squamous, small bowel, non-Hodgkin’s lymphoma,
EATL, or adenocarcinomas); speaker predicts capsule endoscopy will become important test
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| Management: pneumonic CELIAC, ie, consultation with skilled dietitian, education about disease, lifelong adherence
to gluten-free diet, identification and treatment of nutritional deficiencies, access to advocacy group, continuous long-
term follow-up by multidisciplinary team
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| Conclusion: consider sprue; serology helpful; consider resistant or refractory sprue; gastroenterologists should play major
role in screening for complications and malignancies
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| INFECTIOUS DIARRHEA —Richard Goodgame, MD, Professor of Medicine, Baylor College of Medicine, Houston
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| Hurricane Katrina evacuees in Astrodome: home to 25 000 evacuees; thousands of healthcare clinicians mobilized to
make evacuees’ stay healthier; many evacuees fragile; in spite of intensive efforts, on day 3 of occupation, young children
and adults began having acute diarrhea; by day 5, >100 patients seen at volunteer clinic; probably thousands of
people developed this syndrome; young physician wanted to work 12-hr shift at Astrodome and took every precaution
(ie, did not eat or drink anything during shift, washed hands before and between every patient, double gloved, and
took prophylactic antibiotics); 36 hr later, developed severe epigastric pain, nausea, vomiting, and profound diarrhea;
had many loose stools during first 24 hr and was completely incapacitated; little better second day of illness; returned
to work on third day; lost 7 lbs as result of illness
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| Solving puzzle: “what is the epidemiologic situation in which this diarrhea occurred and what are the specific clinical features
that we see?” must list all possible viruses, protozoa, and bacteria that cause acute infectious diarrhea, epidemiologic
features (epidemic or sporadic, identified with specific food, institutional outbreak, travel-related or predisposing
conditions), and specific clinical features of disease
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| Astrodome outbreak: clearly epidemic; clinical features classic (ie, upper tract predominating, watery diarrhea without
blood or pus), incubation period of ≈24 hr, but entire illness over in 3 to 4 days, and no protracted diarrhea beyond 1
to 2 wk; possibility 90% that outbreak norovirus
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| Epidemic gastroenteritis: before 1998, Centers for Disease Control and Prevention (CDC) could only collect specimens,
because 90% of all epidemic and sporadic diarrhea undiagnosed
|
| Reverse transcriptase polymerase chain reaction (RTPCR): test for norovirus; when test became available, “overnight”
90% of unknown causes diagnosed as norovirus (previously known as Norwalk virus; small round-structured
virus); test works on food and body fluids
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| Previously undiagnosed epidemics: varied in setting and means of transmission
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| Where did it come from? norovirus responsible for 70% of food-borne outbreaks of diarrhea
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| Oyster epidemic of early 1990s: oysters bioaccumulate pathogens while filtering 9 gallons of seawater/hr; sick fisherman
vomiting and defecating over side of boat; contaminated oysters harvested and distributed across country;
resulted in 200 000 cases of acute norovirus diarrhea
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| Box lunches in Japan: 1500 children consumed box lunches over 2-day period; >50% of children acquired acute norovirus;
norovirus came from boiled broccoli handled with bare hands after cooling
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| Concert hall epidemic: man attending concert in Wales felt belly pain, cramping, and nausea, and vomited into trash
container in lobby; had profuse diarrhea and several more episodes of emesis; went back into concert but could
not stay, had another bout; 36 hr later, 100 people got norovirus (documented aerosolized transmission); concert
hall cleaned but for next 3 nights, people who sat in same and nearby areas got norovirus
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| Other cases: hotels and cruise ships; everyone gets infected but 40% get sick
|
| Pathogenesis of norovirus: only way to stop epidemic is to quarantine location for 5 days; one person can infect everybody
else; always small group of people who cannot be infected, no matter what dose of virus given (has to do with
type B blood group antigen)
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| Clues pathogen not norovirus: blood and pus in stool; illness lasting >1 wk; certain epidemiologic situations, eg, hospital-acquired
or antibiotic-associated diarrhea
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| Hospital-acquired diarrhea: no diagnostic dilemma if patient gets infectious diarrhea after 3 days in hospital; Clostridium
difficile only pathogen worth serious consideration if diarrhea from infectious cause; do not need stool cultures or
fecal smear; clinical features not helpful
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| New strain of C difficile: 3 cities in Canada documented 7-fold increase in frequency and severity of C difficile; 83
deaths in Montreal in one short period in 2003; numerous colectomies reported; ICUs had to be closed; associated
with fluoroquinolone use and proton pump inhibitor (PPI) use (risk for C difficile colitis 3-6 times greater in those taking
PPIs); characteristics of new strain—new toxotype; produces 20 times as much toxin A and toxin B as historical
strain; also produces new toxin called binary toxin; has deletion in regulatory gene that used to stop toxin production
at times of steady growth; has high resistance to clindamycin and fluoroquinolones; represents 90% of isolates in affected
areas; identified in 9 states; associated with high mortality; strongly associated with lack of susceptibility to
metronidazole; disease phenotype (Veterans Affairs [VA] data)—in 2004, incidence of C difficile jumped from 6 per
1000 admissions to 18 per 1000; large increase in colectomies; one third of patients who required colectomy had trivial
or no diarrhea (high levels of toxin cause gut motility to stop); toxin assay negative in 18%; disease progresses on
medical therapy; mortality 50% after colectomy; “when somebody tells us not to use antibiotics or only in certain situations,
we ought to play ball”; practice guidelines—diagnostic vigilance, aggressive treatment, and close monitoring
indicated; obtain bioassay (tissue culture) for C difficile toxin (sensitivity 100%; never has to be repeated; false-negatives
very uncommon; 1- to 3-day test, “but it tells you the right answer”); if another diagnostic study needed, use endoscopy;
stop antibiotics, then start metronidazole (efficacy of 75% best that can be expected); add vancomycin if no
response; better therapies expected
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| Traveler’s diarrhea: 50 million travel to developing countries and 30% to 50% get loose or liquid stools, nausea, vomiting,
abdominal pain, occasionally dysentery; most caused by Escherichia coli; patients should take single dose of levofloxacin
(Levaquin) or azithromycin immediately upon onset of symptoms, plus loperamide (shortens 2-day illness to 12-
hr illness); rifaximin not absorbed, produces little alteration of fecal flora, and has similar efficacy to Levaquin and
azithromycin (final trials not completed); reluctance to recommend prophylaxis due to fears of resistance and systemic
reactions; in study on rifaximin prophylaxis, attack rate reduced from 53% to 15%; if prophylaxis not used, patients have
5% to 25% chance of developing postdysenteric IBS at 6 mo
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| THE ODOR OF FLATUS AND WHAT WE CAN DO ABOUT IT— Michael D. Levitt, MD, Professor of Medicine,
University of Minnesota Medical School, and Associate Chief of Staff for Research, VA Medical Center, Minneapolis
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| How humans detect odor: olfactory area in upper part of nasal cavity contains layer of mucus that contains millions of
cilia; cilia have receptors for various chemicals; do not smell anything until volatile chemical reacts with receptor on
cilia; how one breathes determines how well one can detect odors (ie, little turbulence in cilia during exhalation [why
we do not smell our own breath] and inhalation; sniffing causes greater turbulence and contact with cilia); each cilia
has many receptors specific for any given chemical; when cell fires and impulse goes to brain, brain understands exactly
which chemical stimulated cell; cell and receptors under control of single gene; ability to smell genetically controlled;
≈1000 different genes and olfactory cells enabling ≈1000 different odors to be detected
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| Which compounds cause noxious odor from intestinal gas: placed rectal tube in 6 female and 10 male volunteers and
captured gas in aluminum foil bag (men pass larger volumes of flatus than women; average amount 119 mL for men, 88
mL for women); noxious gases in highest concentration sulfur compounds (ie, hydrogen sulfide, methane sulfide, and
dimethyl sulfide); total amount of noxious gas per pass 4 µL (<0.001% of flatus); used blinded judges to sniff gas in randomized
fashion and rate its odor, then correlated noxiousness of odor with concentration of sulfide gases in flatus;
treated flatus samples with zinc to remove sulfide gases and found that odor decreased significantly; sulfide gases important
but not only compounds that cause noxious odor
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| Sex difference in odor: flatus passed by women tended to have worse odor and higher concentrations of sulfide gases,
compared to men
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| Bismuth: effectively binds sulfide gases; reduces ability of feces to release sulfide gases; could be used short term but
not recommended for long term
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| Charcoal: effectively absorbs every odoriferous compound, but oral charcoal ineffective at decreasing or eliminating odor
of flatus; various external charcoal devices (eg, cushions, underwear, pads) available; speaker studied each of these and
found cushions removed ≈20% of gas, pads removed 60% to 80%, spun-charcoal underpants removed 100%
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Educational Objectives
| The goal of this program is to educate the listener about problems in the gastrointestinal tract. After hearing and assimilating
this program, the clinician will be better able to:
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| 1. List the guidelines for diagnosing celiac disease.
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| 2. Recite a pneumonic for the management of celiac disease.
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| 3. Describe the syndrome caused by norovirus.
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| 4. Discuss the characteristics and management of the new strain of Clostridium difficile.
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| 5. Describe the current methods for decreasing the odor of flatus and list the efficacy of each.
|
Discussed on This Program
Azithromycin [Zithromax, Zmax]
Bismuth subsalicylate (BSS) [Bismatrol, Pepto-Bismol, Pink Bismuth]
Clindamycin (many trade names)
Erythromycin (many trade names)
Levofloxacin [Levaquin, Quixin]
Loperamide HCl (many trade names)
Metronidazole [Flagyl, others]
Rifaximin [Normix, Xifaxan]
Vancomycin [Vancocin, Vancoled]
Programs of Related Interest
Bond JH et al: Three GI stooges: gas, bad breath, nausea. Audio-Digest Gastroenterology 19:09(Sep 1), 2005; Silva
J, Giardiello FM: Chronic diarrhea colon cancer prevention. Audio-Digest Internal Medicine 51:19(Oct 7), 2004; Sinatra
FR: Gastrointestinal update. Audio-Digest Pediatrics 51:24(Dec 21), 2005.
To Order, Contact Subscriber Service (1-800-423-2308)
Suggested Reading
Abenavoli L et al: Cutaneous manifestations in celiac disease. World J Gastroenterol 12:843, 2006; Baudon JJ et al:
Outcome of infants with celiac disease. Gastroenterol Clin Biol 29:1097, 2005; Castelli F et al: Prevention and Treatment
of Traveler’s Diarrhea. Focus on Antimicrobial Agents. Digestion 73 Suppl 1:109, 2006; Chermesh I et al: Probiotics
and the gastrointestinal tract: Where are we in 2005? World J Gastroenterol 12:853, 2006; Grinblat J et al:
Diarrhea in elderly patients due to Clostridium difficile associated with Salmonella and Shigella infection. Arch Gerontol
Geriatr 39:277, 2004; Huebner ES et al: Diagnosis of celiac disease in a patient with fecal incontinence. Nat
Clin Pract Gastroenterol Hepatol 3:172, 2006; Ohge H et al: Effectiveness of devices purported to reduce flatus odor.
Am J Gastroenterol 100:397, 2005; Oldfield EC 3rd: Clostridium difficile-associated diarrhea: risk factors, diagnostic
methods, and treatment. Rev Gastroenterol Disord 4:186, 2004; Penner R et al: Probiotics and nutraceuticals: non-
medicinal treatments of gastrointestinal diseases. Curr Opin Pharmacol 5:596, 2005; Suarez FL et al: Bismuth subsalicylate
markedly decreases hydrogen sulfide release in the human colon. Gastroenterology 114:923, 1998; Suarez
FL et al: Failure of activated charcoal to reduce the release of gases produced by the colonic flora. Am J Gastroenterol
94:208, 1999; Suarez FL et al: Identification of gases responsible for the odour of human flatus and evaluation
of a device purported to reduce this odour. Gut 43:100, 1998.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue,
the speakers reported no conflict.
Drs. Di Palma and Goodgame were recorded at the 30th Annual Texas Program, held in Houston, September 16-18, 2005,
and sponsored by the Texas Society for Gastroenterology and Endoscopy, the American College of Gastroenterology, and
the Texas Regional Societies; Dr. Levitt was recorded at Advances in Gastrointestinal and GI Laparoscopic Surgery,
held in Minneapolis, June 15-18, 2005, and sponsored by the University of Minnesota Medical School. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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