456

Diarrhea
Melissa A. Munsell, MD; Gregory B. Ang, MD; Mark Donowitz, MD;
and Cynthia L. Sears, MD
FAST FACTS
I
Diarrhea is a change in bowel habits with abnormally loose stools,
usually associated with excessive frequency of defecation and more
than 200 g stool per day.
1
I
Diarrhea develops through the following mechanisms: decreased rate
of intestinal nutrient and salt absorption, net electrolyte secretion,
rapid intestinal transit, and the ingestion of poorly absorbable
substances, increasing intraluminal osmotic activity.
2
I
Diarrhea is classified as acute (lasting < 14 days), persistent (14 to
28 days), or chronic (> 4 weeks).
I
Acute diarrhea usually is caused by infection and is self-limited.
It usually does not warrant antibiotics
3
but does necessitate oral
rehydration therapy.
I
Chronic diarrhea is less likely to be caused by infection, is more
often a symptom of other disorders, and is generally classified as
watery, inflammatory, or fatty.
4
I
Watery diarrhea can be further classified as secretory versus
osmotic, which can be distinguished by the response to fasting.
Osmotic diarrhea resolves by 48 hours of fasting, whereas secretory
diarrhea persists after 48 hours of fasting.
5
I. EPIDEMIOLOGY
Globally, diarrheal diseases account for more than 2 million deaths each
year.
6
In the United States, the incidence of diarrheal illness is estimated
to be 1.4 episodes per person per year, or 211,000,000 cases per year.
6
Chronic diarrhea is estimated to affect 3,080,000 people per year in the
United States.
7
Infectious diarrhea is the most common cause of diarrhea
worldwide.
2
II. ACUTE DIARRHEA: CLINICAL PRESENTATION AND DIAGNOSIS
1. Presentation. Acute diarrhea can be classified as noninflammatory or
inflammatory diarrhea.
a. Noninflammatory infectious diarrhea presents with watery diarrhea that
may be more than 1 L per day. It is usually self-limited and is not
associated with severe abdominal pain or stool containing blood or pus.
Fever can be variable.
1
b. Inflammatory diarrhea may present with watery diarrhea or dysentery.
Dysentery is frequent, small-volume stools that are mucoid or bloody
and may be accompanied by fever, severe abdominal pain, and
tenesmus.
1
39
A03748-ch039.qxd 2/14/06 12:01 PM Page 456
2. The history should focus on relevant clinical and epidemiologic
features.
a. Relevant clinical features include when and how the illness began,
stool characteristics, frequency of bowel movements, stool quantity,
presence of dysenteric symptoms, and symptoms of volume depletion.
b. Relevant epidemiologic features include travel history, day care center
contact, consumption of uncooked foods (e.g., raw or uncooked meat
or seafood, unpasteurized milk products or apple cider, and foods sitting
at room temperature more than 2 hours), swimming or drinking from a
lake or stream, animal contact, sick contacts, medications, human
immunodeficiency virus infection, or immunosuppression.
8
3. The physical examination generally is not helpful in making a specific
diagnosis but is used to assess the patients volume status: orthostatic
vital signs, dry mucus membranes, resting tachycardia, and skin turgor.
The abdominal examination should assess bowel sounds, tenderness,
and distension. Examination should also include visual inspection of the
stool and occult blood determination.
4. Laboratory findings.
a. Leukocytosis with a left shift suggests an inflammatory cause because
noninflammatory diarrhea generally is associated with a normal white
blood cell count.
b. Serum electrolytes, urea nitrogen, and creatinine should be analyzed for
evidence of volume contraction, renal failure, and electrolyte depletion.
5. Etiology (Table 39-1
8,9
and Box 39-1).
6. Evaluation. Most cases of acute diarrhea last less than 24 hours and
do not warrant investigation. Thorough evaluation should be undertaken
in patients with more severe illness, as indicated by any of the
following features:
I
Profuse, watery diarrhea with volume depletion, as evidenced by
orthostatic hypotension.
I
Dysentery (frequent stools with blood and mucus).
I
Fever.
I
Diarrhea with severe abdominal pain.
I
Diarrhea in older adults.
I
Immunocompromised patients (e.g., acquired immunodeficiency
syndrome, posttransplant state, chemotherapy, diabetes).
a. A careful history and laboratory evaluation will aid in the diagnosis
and management of acute diarrhea. Laboratory evaluation should be
undertaken in patients who are severely ill, those meeting the criteria
outlined earlier, or those with a prior history of antibiotic therapy.
b. Stool examination.
(1) Stool cultures should be obtained in patients meeting the criteria
outlined earlier, those appearing clinically ill, or those with stools
positive for fecal leukocytes, lactoferrin, or occult blood.
10
(2) Evaluation of stools for ova and parasites (O & P) is indicated in
the setting of persistent or chronic diarrhea, travel to developing
Diarrhea
457
39
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A03748-ch039.qxd 2/14/06 12:01 PM Page 457
458
Gastroenterology
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Diarrhea
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Gastroenterology
countries or mountainous areas, exposure to children attending day
care centers, receptive anal intercourse, acquired immunodeficiency
syndrome, other immune-compromised states, community
waterborne outbreaks, and bloody diarrhea with few or no fecal
leukocytes. There is no utility of evaluation for O & P in patients
with onset of diarrhea > 72 hours after hospitalization.
(3) Evaluation for Clostridium difficile toxin is indicated in patients
who have received antimicrobial therapy within the past 2 months
and patients hospitalized for more than 72 hours. Generally, two
consecutive stool examinations have a sensitivity of 90% in
detecting C. difficile.
12
c. Flexible sigmoidoscopy with or without upper gastrointestinal
endoscopy should be considered for recipients of anal intercourse,
immunocompromised hosts, and patients with persistent diarrhea
(> 14 days) not responding to antimicrobial therapy or without a
diagnosis after laboratory evaluation, including at least two complete
stool examinations for culture, ova and parasites, and C. difficile.
d. In patients who appear to have been exposed to toxins, abdominal
radiographs or abdominal computed tomograms should be obtained
to evaluate for the presence and extent of colitis and to evaluate for
megacolon or ileus.
13
III. ACUTE INFECTIOUS DIARRHEA: MANAGEMENT
1. The management of patients with diarrhea who need medical
evaluation and are volume depleted begins with rehydration.
2. According to the Infectious Diseases Society of America, the preferred
form of fluid replacement is an oral glucose- or starch-containing
electrolyte solution (oral rehydration solution) such as Ceralyte or
Pedialyte.
8
3. Empiric antibiotics may be considered in the following patients.
a. Travelers diarrhea can be treated with fluoroquinolone therapy (e.g.,
oral ciprofloxacin 500 mg twice a day) because it can reduce the
duration of illness from 3 to 5 days to less than 2 days according to
Infectious Diseases Society of America guidelines.
8
Alternatively,
BOX 39-1
DIFFERENTIAL DIAGNOSIS OF ACUTE NONINFECTIOUS DIARRHEA
Drugs and toxins (e.g., magnesium, caffeine, theophylline, laxatives, opiates,
lactulose, colchicine, metformin, digitalis, iron, methyldopa, hydralazine, sorbitol,
quinidine, fructose, mannitol, arsenic, cadmium, mercury, mushrooms)
Irritable bowel syndrome
Inflammatory bowel disease
Ischemic bowel disease
Food allergies
Lactase deficiency
Onset of chronic diarrhea of any cause (e.g., vasoactive intestinal peptidesecreting
tumor)
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travelers can prophylactically take bismuth subsalicylate (one to two
262-mg tablets four times a day), which has been shown to decrease
the incidence of travelers diarrhea by 35% to 65% and appears to be
safe for up to 3 weeks.
6
b. Patients with diarrhea lasting longer than 10 days, in whom giardiasis
is suspected and other evaluations are negative, may be treated
empirically with metronidazole 250 to 750 mg orally three times a day
for 7 days.
8
c. Patients with severe febrile diarrheal illnesses may be treated
empirically with a fluoroquinolone if they appear toxic or unstable.
If possible, antibiotic therapy should be delayed until Shiga
toxinproducing Escherichia coli is ruled out by fecal testing because
of concern for increased risk of hemolytic-uremic syndrome (HUS).
9
If
intravenous therapy is deemed necessary because of systemic toxicity
(e.g., salmonellosis), a fluoroquinolone or intravenous third-generation
cephalosporin is reasonable empiric treatment.
4. Use of antimotility agents.
a. Adults with nondysenteric diarrhea can be given antimotility agents
such as loperamide (4 mg initially, then 2 mg after each unformed
stool, not to exceed 16 mg daily) or diphenoxylate with atropine (4 mg
four times a day) without ill effect.
b. Antimotility agents should be avoided in patients with bloody diarrhea
or proven infection with Shiga toxinproducing E. coli or Clostridium
difficile.
8
c. In children and older adults with enterohemorrhagic E. coli infection,
antimotility agents may trigger HUS
14
and lead to worsening neurologic
symptoms.
15
5. Culture-directed antimicrobial therapy is used when specific pathogens
are identified in stool samples and illness has not resolved (see Table
39-1). Of the four leading bacterial pathogens (Salmonella, Shigella,
Campylobacter jejuni, and Shiga toxinproducing E. coli), only Shigella
spp. infection is routinely treated. Treating Salmonella with antibiotic
therapy increases the frequency and duration of intestinal carriage of
the organisms.
6. A systematic approach to the evaluation and management of acute
diarrhea is outlined in Fig. 39-1.
16-18
IV. CHRONIC DIARRHEA: DIAGNOSIS
1. Diarrhea of more than 4 weeks duration warrants an evaluation for
chronic diarrheal illnesses.
5
The evaluation of patients with chronic
diarrhea is more complex than that of patients with acute diarrhea
because of the broad range of possible causes (Box 39-2).
2. Any acute infectious diarrhea can lead to chronic diarrhea; therefore the
first step in evaluating chronic diarrhea is to rule out infectious causes.
3. Stool samples should be taken at two separate times for cultures,
three times for O & P, acid-fast staining (to evaluate for Cryptosporidium,
Cyclospora, and Isospora belli), and Giardia antigen testing (enzyme-
Diarrhea
461
39
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R
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E
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Gastroenterology
Approach to acute diarrhea. *Send stool for Clostridium difficile toxin test if the
patient has a history of antibiotic use within the past 2 months. Twenty-five percent
of C. difficile disease occurs in the outpatient setting. Of patients with Shigella,
Salmonella, and C. difficile infections, 30% or more do not have fecal leukocytes or
occult blood.
17,18
(Modified from Guerrant RL, Bobak DA: N Engl J Med 325:327,
1991.)
Present Absent
Acute diarrhea
Symptomatic therapy
(rehydration, preferably with oral rehydration solutions)
Severe dehydration, fever, blood, weight loss
History and physical examination: consider infectious and
noninfectious causes (see Box 39-1 and Table 39-1)
Send stool for fecal leukocytes and occult blood*
Noninflammatory
(Norwalk virus, rotavirus,
Escherichia coli,
Clostridium perfringens,
Bacillus cereus, Giardia,
Cryptosporidium)
Continue
symptomatic therapy
Stool cultures, examination
for ova and parasites
if symptoms persist
Inflammatory
(Shigella, Salmonella,
Clostridium jejuni,
Shiga toxinproducing
E. coli, Clostridium difficile)
Stool cultures; consider
examination
for ova and parasites
Consider empirical
antimicrobial
therapy
Specific therapy
once pathogen
identified
Consider sigmoidoscopy endoscopy
if diarrhea persists (> 14 days) or
does not respond to antimicrobials
and laboratory evaluation is negative;
consider noninfectious causes
FIG. 39-1
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463
39
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I
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E
A
linked immunosorbent assay). C. difficile testing should be performed if
there has been any antibiotic use within the past 2 months.
4. A lactose-free diet should be followed for several days because acute
diarrhea may lead to secondary lactase deficiency.
5
5. Along with excluding infectious causes and lactase deficiency, previous
gastric surgery, ileal resection, medications, and systemic disease
should be excluded as causes of chronic diarrhea.
5
6. In addition to the history, physical examination, and routine laboratory
blood work, a quantitative stool collection and analysis often are
necessary to classify the diarrhea and to assist in making a specific
diagnosis once infectious causes have been excluded (Table 39-2).
19
7. Additional blood, urine, radiologic, endoscopic, or other studies may be
considered for further evaluation of chronic diarrhea (Table 39-3).
8. The response to fasting often is used to distinguish secretory from
nonsecretory diarrhea. Secretory diarrhea persists after 48 hours of
fasting, whereas nonsecretory diarrhea ceases by 48 hours of fasting.
5
BOX 39-2
CAUSES OF CHRONIC DIARRHEA
OSMOTIC WATERY DIARRHEA
Osmotic laxatives (magnesium, phosphate, sulfate)
Carbohydrate malabsorption
SECRETORY WATERY DIARRHEA
Congenital syndromes
Bacterial toxins
Inflammatory bowel disease
Vasculitis
Drugs and poisons (see Box 39-1)
Laxative abuse
Disordered motility or regulation
Endocrine diarrhea (hyperthyroidism, hypothyroidism, Addisons disease,
gastrinoma, vasoactive intestinal peptidesecreting tumor, somatostatinoma,
carcinoid syndrome, medullary thyroid carcinoma, mastocytosis)
Other tumors (colon carcinoma, lymphoma, villous adenoma)
IDIOPATHIC SECRETORY DIARRHEA
Epidemic secretory (Brainerds) diarrhea
INFLAMMATORY DIARRHEA
Inflammatory bowel disease
Infectious diseases
Ischemic colitis
Radiation colitis
FATTY DIARRHEA (50% WATERY)
Malabsorption syndromes (celiac disease, Whipples disease, short bowel
syndrome, small bowel bacterial overgrowth)
Maldigestion (pancreatic exocrine insufficiency, inadequate luminal bile acids)
Modified from Schiller LR: Med Clin North Am 84:1259, 2000.
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V. CHRONIC DIARRHEA: MANAGEMENT
1. As with acute diarrhea, patients with chronic diarrhea must receive
adequate hydration, preferably with an oral rehydration solution.
2. Empiric therapy is advocated for patients with chronic diarrhea in the
following situations
4
:
a. As initial or temporizing therapy before diagnostic testing.
b. After exhaustive investigation fails to reveal a specific cause.
c. When a diagnosis has been made but no specific treatment is available
or specific treatment fails.
10
3. Empiric treatment may include the following:
a. Antibiotics (e.g., metronidazole, fluoroquinolones, or TMP-SMX) if
bacterial or protozoal infection is suspected based on the patients
history.
b. Opiates (e.g., loperamide) for symptomatic control.
c. Bile acidbinding resins (e.g., cholestyramine).
d. Octreotide is used as a secondary agent, usually in secretory diarrhea,
dumping syndrome, and chemotherapy-induced diarrhea.
PEARLS AND PITFALLS
I
Antibiotic prophylaxis is not recommended for healthy people traveling
to high-risk areas unless the traveler has significant predisposing illness
such as acquired immunodeficiency syndrome, inflammatory bowel
TABLE 39-2
STOOL STUDIES IN NONINFECTIOUS CHRONIC DIARRHEA
Study Comments
Stool Na
+
, K
+
Osmotic gap < 50 mOsm/kg suggests secretory
diarrhea; > 50 mOsm/kg suggests osmotic
diarrhea; fecal osmotic gap = 290 - 2(stool Na
+
+ K
+
).*
Stool pH pH < 5.6 suggests carbohydrate malabsorption.*
Fecal occult blood Positive test suggests the presence of inflammatory
bowel disease, neoplastic diseases, ischemia,
radiation.
Fecal leukocytes Presence suggests inflammatory or infectious
diarrhea.
Sudan stain; 72-hr fecal fat Steatorrhea (> 14 g fat/d) indicates malabsorption
(on 75- to 100-g fat/d diet) (normally < 7 g fat/d); 7-14 g fat/day may result
from large stool volume.
Stool alkalinization or Evaluation for laxative abuse (bisacodyl,
thin-layer chromatography phenolphthalein, anthraquinones).
Stool weight Diarrhea defined by stool weight > 200 g/d.
Stool osmolality Osmolality < 250 mOsm/kg implies dilution of stool
with water or urine.
Stool Mg
+
, sulfate, phosphate Stool Mg
+
> 45 mM suggests inadvertent Mg
+
ingestion in mineral supplements or antacids or
surreptitious laxative abuse.
*Data from Eherer AJ, Fordtran JS: Gastroenterology 103:545, 1992.
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39
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disease, hypochlorhydria secondary to prior gastric surgery or use of a
proton pump inhibitor, insulin-dependent diabetes mellitus, or severe
vascular, cardiac, or renal disease or malignancy.
20
Fluoroquinolones are
the agent of choice for travelers diarrhea unless the patient is traveling
to southeast Asia, where more than 90% of Campylobacter strains are
quinolone resistant.
21,22
I
Symptomatic food handlers and health care workers with acute,
presumed infectious diarrhea should be barred from directly handling
food and from caring for patients. Asymptomatic food handlers and
health care workers with diagnosed Salmonella should have two
consecutive negative stool samples taken 24 hours apart and at least
48 hours after resolution of symptoms before returning to their jobs.
8
I
Patients with diarrhea who have been the recipients of anal
intercourse are at risk for proctitis and colitis resulting from direct
rectal inoculation of pathogens. In addition to the more common
bacterial enteropathogens, Neisseria gonorrhoeae, Chlamydia
trachomatis, herpes simplex virus, and Treponema pallidum should be
considered as causative agents.
I
Immunocompromised patients, such as transplant recipients, patients
undergoing chemotherapy, patients with human immunodeficiency virus
infection, and patients with primary immunodeficiencies, are susceptible
to an additional range of pathogens, which are beyond the scope of this
chapter (see Chapter 51 and Chapter 62).
TABLE 39-3
ADDITIONAL STUDIES IN EVALUATING CHRONIC DIARRHEA
Radiologic Urine Blood Endoscopic Other
Abdominal 5-HIAA (for Gastrin,* Sigmoidoscopy Test of bile
radiographic carcinoid calcitonin,* with biopsy acid or other
findings (for syndrome) VIP,* breath test
pancreatic somatostatin* for bacterial
calcification) overgrowth
Barium studies Thin-layer Thyroid Colonoscopy Nutritionist-
of the upper chromatography function tests and ileoscopy supervised
gastrointestinal (for laxatives) with biopsy lactose-free
tract, small (for right-sided diet for
bowel, and colitis, 3-5 d
colon amebiasis,
Crohns disease,
and microscopic
and collagenous
colitis)
Abdominal Upper endoscopy,
computed including small
tomography bowel biopsy
5-HIAA, 5-hydroxyindoleacetic acid; VIP, vasoactive intestinal peptide.
*Should not be performed unless stool volume is >1 L/day or severe hypokalemia is present.
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