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Approach to the adult with chronic diarrhea

in resource-abundant settings
Approach to the adult with chronic diarrhea in resource-abundant settings
Authors:
Peter A L Bonis, MD
J Thomas Lamont, MD
Section Editor:
Lawrence S Friedman, MD
Deputy Editor:
Shilpa Grover, MD, MPH, AGAF
Literature review current through: Dec 2022. | This topic last updated: May 02, 2022.
INTRODUCTION — Diarrhea is a common manifestation of gastrointestinal

disease and is a leading cause of health care utilization [1,2]. Optimal strategies for the
evaluation of patients with chronic diarrhea have not been established. The selection of
specific tests, timing of referral, and the extent to which testing should be performed
depend upon an appraisal of the likelihood of a specific diagnosis, the availability of
treatment, the severity of symptoms, patient preference, and comorbidities. However, a
specific diagnosis can be achieved in more than 90 percent of patients.
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This topic review will provide an overview of the evaluation and treatment of chronic
diarrhea. Individual disorders associated with chronic diarrhea and an approach to patients
with acute diarrhea are presented separately. (See "Epidemiology, pathogenesis, and clinical
manifestations of celiac disease in adults" and "Microscopic (lymphocytic and collagenous)
colitis: Clinical manifestations, diagnosis, and management" and "Clinical manifestations,
diagnosis, and prognosis of ulcerative colitis in adults" and "Clinical manifestations,
diagnosis, and prognosis of Crohn disease in adults" and "Evaluation of the patient with HIV
and diarrhea" and "Approach to the adult with acute diarrhea in resource-rich settings".)
DEFINITION — Chronic diarrhea is defined as a persistent alteration of stool

consistency from the norm with loose stools (consistency between types 5 and 7 on the
Bristol stool chart) and increased stool frequency of greater than three stools daily of at
least four weeks' duration [3-7].
EPIDEMIOLOGY — The prevalence of chronic diarrhea in the general

population in resource-abundant settings has not been well established. The variable rates
observed in several studies reflect differences in study design, definitions, and
characteristics of populations that have been sampled. Based upon a commonly used
definition (ie, the presence of excessive stool frequency) a reasonable approximation is that
chronic diarrhea affects approximately 3 to 7 percent of the population [4,8,9]. Chronic
diarrhea can decrease quality of life. However, accurate assessment of the degree to which
this occurs has not been established. Direct and indirect costs of chronic diarrhea in the
United States are estimated to be at least $524 million per year and $136 million per year,
respectively [10-12].
ETIOLOGY — The principal causes of diarrhea vary based upon the

socioeconomic status of the population. In resource-abundant settings, common causes are
irritable bowel syndrome (IBS), inflammatory bowel disease, malabsorption syndromes
(such as lactose intolerance and celiac disease), and chronic infections (particularly in
patients who are immunocompromised) (table 1). In resource-limited settings, chronic
diarrhea is frequently caused by chronic bacterial, mycobacterial, and parasitic infections,
although functional disorders, malabsorption, and inflammatory bowel disease are also
common.
The following sections highlight important distinguishing clinical features of some the most
prevalent disorders associated with chronic diarrhea. Other less prevalent causes are listed
in the table (table 1). Detailed discussions on these and other disorders associated with
chronic diarrhea are presented in the corresponding topic reviews.
Functional disorders — Patients with IBS complain of cramping

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quadrant pain associated with altered bowel habits (diarrhea, constipation, alternating
diarrhea and constipation). Diarrhea is usually characterized as frequent loose stools of
small to moderate volume. Stools generally occur during waking hours, most often in the
morning or after meals. Some bowel movements are preceded by extreme urgency and
may be followed by a feeling of incomplete evacuation or tenesmus. Incontinence of liquid
stool may occur during periods of disease activity. Approximately one-half of all patients
with IBS complain of mucus discharge with stools. Symptoms of IBS often correlate with
episodes of psychologic stress. Thus, patients often seek medical help for their chronic
symptoms during such periods. Patients usually experience the onset of symptoms as
young adults, but the prevalence is similar in older adults. Post-infectious IBS can occur
following recovery from Clostridioides difficile and other bacterial infections. (See "Clinical
manifestations and diagnosis of irritable bowel syndrome in adults" and "Pathophysiology
of irritable bowel syndrome".)
A number of related functional bowel disorders have also been described to include
functional diarrhea, IBS with predominant diarrhea, and IBS with mixed bowel habits [13].
These disorders are considered to represent a continuum, rather than being independent
entities, according to a consensus of experts [14,15]. Functional diarrhea is characterized by
recurrent passage of loose or watery stools. Patients with functional diarrhea should not
meet criteria for IBS. Patients with functional diarrhea may have abdominal pain and/or
bloating, but unlike IBS, these are not predominant symptoms.
Organic disorders — Organic disorders are conditions that are associated with

physiologic, structural, or biochemical abnormalities. Organic disorders are more likely in
adults with "alarm" features (table 2). (See 'Evaluation for alarm features' below.)
Inflammatory bowel disease — Inflammatory bowel disease (IBD) primarily

refers to ulcerative colitis and Crohn disease, although other intestinal disorders are also
associated with intestinal inflammation. Most cases of ulcerative colitis and Crohn disease
have their onset between ages 15 and 40. Many studies suggest a bimodal age distribution
for both disorders with a second peak between age 50 and 80. IBD tends to run in families
and is more common in individuals with Jewish ancestry. (See "Definitions, epidemiology,
and risk factors for inflammatory bowel disease".)
●Crohn disease – Crohn disease may involve the entire gastrointestinal tract from mouth to
perianal area. Diarrhea, abdominal pain, weight loss, and fever are the typical clinical
manifestations for most patients with ileitis, ileocolitis, or Crohn colitis. Patients can have
symptoms for many years prior to diagnosis. Although occult GI blood loss is common in
Crohn disease, gross bleeding is much less frequent than in ulcerative colitis (except for
some patients with Crohn colitis).
●Ulcerative colitis – Patients with ulcerative colitis may present in a variable manner. The
history is typically one of the gradual onset of symptoms, sometimes preceded by a self-
limited episode of rectal bleeding that occurred weeks or months earlier. The initial episode
is limited to the rectum or distal colon in one-third of patients, to the left colon up to the
splenic flexure in one-third, and most of the remaining patients have pancolitis. Less than
10 percent present with fulminant disease. (See "Clinical manifestations, diagnosis, and
prognosis of ulcerative colitis in adults".)
Microscopic colitis — Microscopic colitis usually occurs in middle-aged and older

adults, but it can also affect children. Microscopic colitis has two main histologic subtypes
(lymphocytic colitis and collagenous colitis). Both subtypes have a similar clinical
presentation. Patients with microscopic colitis usually have between four and nine watery
stools per day, but in rare cases, bowel movements can exceed 1.5 or up to 2 liters per day.
The clinical course is mainly intermittent. (See "Microscopic (lymphocytic and collagenous)
colitis: Clinical manifestations, diagnosis, and management", section on 'Clinical
manifestations'.)
Colonoscopy usually reveals macroscopically normal colonic mucosa, although slight

edema, erythema, and friability may be seen. Although specimens obtained by flexible
sigmoidoscopy are frequently sufficient to establish the diagnosis, the severity of histologic
changes declines from the proximal to the distal colon; thus, colonoscopic biopsies should
be obtained from the entire colon. (See "Microscopic (lymphocytic and collagenous) colitis:
Clinical manifestations, diagnosis, and management", section on 'Diagnostic approach' and
'Endoscopic evaluation' below.)
Malabsorption syndromes — The classic manifestations of malabsorption

are pale, greasy, voluminous, foul-smelling stools, and weight loss despite adequate food
intake. However, this spectrum of findings is relatively uncommon, even in generalized
mucosal disease. The majority of patients with malabsorption have relatively mild
gastrointestinal symptoms, which often mimic more common disorders such as IBS. In
some cases, flatulence, abdominal distension, and borborygmi may be the only complaints
suggesting malabsorption; other patients may be asymptomatic. (See "Approach to the
adult patient with suspected malabsorption".)
The clinical and laboratory features of malabsorption depend upon the cause and severity
of the disease (table 3). As an example, isolated forms of malabsorption may present solely
with symptoms that are attributable to the particular nutrient in question (table 4). Iron
deficiency anemia may be the only clue to the presence of celiac disease. (See
"Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults".)
Relatively common disorders associated with malabsorption include:
●Lactose intolerance (see "Lactose intolerance and malabsorption: Clinical manifestations,

diagnosis, and management")
●Chronic pancreatitis (see "Chronic pancreatitis: Clinical manifestations and diagnosis in

adults")
●Celiac disease (see "Epidemiology, pathogenesis, and clinical manifestations of celiac

disease in adults")
●Bacterial overgrowth of the small intestine (see "Small intestinal bacterial overgrowth:
Clinical manifestations and diagnosis")
Post-cholecystectomy diarrhea — The incidence of diarrhea following

cholecystectomy has ranged from as low as 2 percent to as high as 50 percent in various
reports reflecting the various populations, differences in study design, and the degree to
which diarrhea was sought [16-18]. In many cases, the diarrhea will resolve or significantly
improve over the course of weeks to months [19]. The diarrhea is related to excessive bile
acids entering the colon [20,21]. In the absence of a gallbladder, bile drains directly and
more continuously into the small bowel, which may overcome the terminal ileum's
reabsorptive capacity. The increased bile acids in the colon lead to diarrhea (cholerheic
diarrhea) [22]. Patients often respond to treatment with bile-acid binding resins such as
cholestyramine or colestipol [23]. (See 'Empiric therapy in selected patients' below.)
Chronic infections — Some persisting infections (eg, C. difficile, Aeromonas,

Plesiomonas, Campylobacter, Giardia, Amebae, Cryptosporidium, Whipple's disease, and
Cyclospora) can be associated with chronic diarrhea [24]. Microsporidium should be a
consideration in immunocompromised patients with persistent diarrhea. (See appropriate
topic reviews).
Several other causes of chronic diarrhea caused by, or resulting from a presumed infection
have been described:
●An epidemic form of secretory diarrhea (Brainerd diarrhea) associated with patchy
lymphocytic colonic inflammation can cause symptoms that persist for up to three years
[25-30]. Risk factors include consumption of contaminated water and unpasteurized milk.
An infectious agent is suspected but has not been identified.
●The development of post-infectious irritable bowel syndrome has also been described in
up to 30 percent of patients following documented acute bacterial enteric infections. (See
"Pathophysiology of irritable bowel syndrome" and 'Functional disorders' above.)
●It is possible that some patients with chronic diarrhea may have an infectious cause that
may not be easily demonstrable. A case report described a woman with severe, debilitating
diarrhea that was ultimately found to be due to Stenotrophomonas maltophilia, a Gram-

negative rod that was only identifiable using molecular genetic techniques [31]. Further
studies using such techniques will help determine whether other infectious agents can be
implicated in chronic diarrhea.
●Chronic diarrhea due to Candida albicans infection has been described in case reports [32].
Most patients had received immunosuppression (in some cases with antibiotics), were
malnourished, or had an immune disorder [32]. Diagnosis was established by detection of
large numbers of Candida in small bowel aspirates and stool specimens, and response to
antifungal therapy. The presence of Candida in stool specimens has also been described in
asymptomatic individuals, and thus, the clinical context is important in considering the
diagnosis.
●Chronic infection with Blastocystis hominis, an anaerobic protozoan parasite, has been
implicated as a cause of chronic diarrhea in some reports. (See "Blastocystis species".)
Medications — Many drugs can cause diarrhea through a variety of mechanisms [33-

37]. It can be challenging to identify the agent causing drug-induced diarrhea, particularly
in patients taking multiple medications (table 5). The clinical setting and timing of the onset
of symptoms relative to when the medications were started can be helpful.
INDICATIONS FOR REFERRAL TO A

GASTROENTEROLOGIST — The need for gastroenterology
evaluation and timing of referral depend upon the severity of symptoms, the diagnoses
being considered, and the presence of alarm features (table 2). (See 'Evaluation for alarm
features' below and 'Establishing a diagnosis' below.)
Indications for referral include anyone of the following:
•Alarm features
•Severe diarrhea
•Suspected inflammatory bowel disease (see 'Inflammatory bowel disease' above)
•Inconclusive diagnosis after initial evaluation (see 'Initial evaluation' below and
'Establishing a diagnosis' below)
•Failure to respond to empiric therapy (see 'Empiric therapy in selected patients' below)
Referral to a gastroenterologist may also be appropriate in patients who require long-term

management for the underlying cause (eg, inflammatory bowel disease, chronic
pancreatitis).
INITIAL EVALUATION
Overview — The initial evaluation of patient with chronic diarrhea includes history,
physical examination, and laboratory testing to determine whether the patient has any
alarm findings which help to distinguish organic from functional diarrhea and
characterizing the diarrhea in order to direct the need for additional evaluation.
Evaluation for alarm features — Alarm features in patients with chronic

diarrhea may be suggestive of an underlying organic etiology (table 2). These features
include the following (see 'Organic disorders' above):
•Age of onset after age 50 years
•Rectal bleeding or melena [6]
•Nocturnal pain or diarrhea
•Progressive abdominal pain
•Unexplained weight loss, fever, or other systemic symptoms
•Laboratory abnormalities (iron deficiency anemia, elevated C-reactive protein or fecal

calprotectin)
•Family history of inflammatory bowel disease (IBD) or colorectal cancer
Characterizing the diarrhea type — Information other than alarm

features obtained in the initial evaluation helps to distinguish among organic etiologies.
Characterizing the diarrhea (infectious, inflammatory, osmotic, secretory) is a useful way to
guide evaluation and the diagnosis can then be confirmed by focused testing (table 6). The
distinction between types of diarrhea can often be made based upon the medical history
but in other cases may require additional laboratory evaluation. (See 'Laboratory evaluation'
below.)
●Watery diarrhea – The water content of chronic diarrhea can be caused by secretory or
osmotic processes, or a combination of the two. These categories are useful to narrow the
diagnostic possibilities. However, the clinical utility of these categories and their diagnostic
markers is limited because some diarrheal diseases involve a combination of both
processes. If needed, it is possible to distinguish between these processes by measurement
of fecal electrolytes, pH, reducing substances, and calculation of the osmotic gap. (See
'Laboratory evaluation' below.)
•Secretory – Secretory diarrhea is usually associated with large volumes of watery stools
and persists during fasting. Consequently, it is helpful to assess the effects of fasting on
stool output. Pure secretory diarrheas are uncommon, but can occur in the setting of
certain enteric infections. Secretory diarrhea occurs in 80 percent of patients with carcinoid
syndrome and is often the most debilitating component of the syndrome. Stools may vary
from few to more than 30 per day, are typically watery and nonbloody, and can be explosive
and accompanied by abdominal cramping. The abdominal cramps may be a consequence of
mesenteric fibrosis or intestinal blockage by the primary tumor. The diarrhea is usually
unrelated to flushing episodes.
•Osmotic – Osmotic (or "substrate-induced" or "diet-related") diarrhea typically is less

voluminous than secretory diarrhea (eg, <200 mL per day), and improves or resolves during
12- to 24-hours of fasting. The presence of reducing substances or low fecal pH (ie, pH <6)
suggest carbohydrate malabsorption. Osmotic diarrheas are characterized by relatively low
sodium concentration (<70 mEq/L) and a high osmotic gap (>75 mOsm/kg) but testing stool
osmolality is not routinely required. (See 'Laboratory evaluation' below.)
●Fatty diarrhea – Malabsorption is often accompanied by steatorrhea and the passage of

bulky malodorous pale stools. However, milder forms of malabsorption may not result in
any reported stool abnormality. (See "Approach to the adult patient with suspected
malabsorption".)
●Inflammatory diarrhea – Inflammatory forms of diarrhea typically present with liquid

loose stools with blood. Elevation in fecal calprotectin (a protein found in neutrophil
granulocytes) indicates an inflammatory diarrhea. The presence of occult blood also raises
this possibility but is less specific. (See 'General laboratory tests' below.)
History — The initial evaluation of patients who present to medical care with chronic
diarrhea should include a careful history to determine the duration of symptoms, the
frequency and characteristics of the stool, and the presence of associated symptoms. Fecal
incontinence is frequently misinterpreted as diarrhea. A thorough medical history can guide
appropriate evaluation. Important components of the history include the following (table 7):
Symptom characteristics
•A clear understanding of what led the patient to complain of diarrhea (eg, consistency or
frequency of stools, the presence of urgency or fecal incontinence).
•Stool characteristics (eg, greasy stools that float and are malodorous may suggest fat
malabsorption, while the presence of visible blood may suggest an inflammatory cause of
diarrhea). Patients with carbohydrate malabsorption (eg, lactose malabsorption) may be
present with watery diarrhea, excess flatus, and bloating. (See 'Characterizing the diarrhea
type' above and 'Malabsorption syndromes' above and "Approach to the adult patient with
suspected malabsorption".)
•Duration of symptoms, nature of onset (sudden or gradual).
•Occurrence of diarrhea during fasting or at night suggests a secretory or inflammatory

diarrhea. (See 'Characterizing the diarrhea type' above.)
•The volume of the diarrhea (eg, voluminous watery diarrhea is more likely to be due to a
disorder in the small bowel, while small-volume frequent diarrhea is more likely to be due to
disorders of the colon).
•The presence of bloody diarrhea favors a colonic versus small bowel disorder.
•The presence of weight loss and other systemic symptoms may indicate IBD (eg, fevers,
joint pains, mouth ulcers, eye redness).
•Association of stress and depression with onset and severity of the diarrhea suggests a
functional disorder such as irritable bowel syndrome. Irritable bowel syndrome (IBS) is
characterized by chronic abdominal pain and altered bowel habits. Symptoms of IBS include
diarrhea, constipation, alternating diarrhea and constipation, or normal bowel habits
alternating with either diarrhea and/or constipation. (See 'Functional disorders' above and
"Clinical manifestations and diagnosis of irritable bowel syndrome in adults", section on
'History and physical examination'.)
Risk factors
•Travel to a resource-limited setting increases the risk of bacterial diarrhea and also informs
the risk of certain parasitic infections. (See 'Characterizing the diarrhea type' above.)
•History of Clostridiodes (formerly Clostridium difficile) infection and risk factors for C.
difficile. (See "Clostridioides difficile infection in adults: Epidemiology, microbiology, and
pathophysiology", section on 'Risk factors'.)
•All medications (including over-the-counter drugs and supplements) (table 5) [2].
•Dietary history should include possible use of sorbitol-containing products, food additives
including fructose and other fermentable oligo-, di-, mono-saccharides and polyols, alcohol
and association of symptoms with specific food ingestion (eg, dairy products or potential
food allergens) (table 8).
•Medical history:
-A history of or risk factors for sexually transmitted diseases. As examples, Neisseria

gonorrhoeae and herpes simplex virus are associated with proctitis. HIV infection is
associated with diarrhea due to infectious agents but may also be due to infiltrative
diseases, such as lymphoma or Kaposi's sarcoma or antiretroviral medication use. (See
"Evaluation of the patient with HIV and diarrhea".)
-A history of recurrent bacterial infections (eg, sinusitis, pneumonia), which may indicate a
primary immunoglobulin deficiency. (See "Clinical manifestations, epidemiology, and
diagnosis of common variable immunodeficiency in adults".)
-A history of chronic diseases associated with amyloidosis (eg, chronic degenerative

arthropathies, particularly rheumatoid arthritis, ankylosing spondylitis and psoriatic
arthritis and plasma cell dyscrasias). (See "Gastrointestinal amyloidosis: Clinical
manifestations, diagnosis, and management", section on 'Gastrointestinal tract
amyloidosis'.)
-In patients with a history of an allogeneic hematopoietic cell transplant, graft versus host
disease and among recipients of umbilical cord blood, cord colitis syndrome can cause
diarrhea. Radiation enteritis can also cause chronic diarrhea, and in some cases can occur
several years after treatment. (See "Clinical manifestations and diagnosis of chronic graft-
versus-host disease", section on 'Gastrointestinal tract' and "Overview of gastrointestinal
toxicity of radiation therapy", section on 'Enteritis' and "Diagnosis and management of
chronic radiation enteritis", section on 'Management' and "Early complications of
hematopoietic cell transplantation", section on 'Cord colitis syndrome'.)
-Prior gastrointestinal surgeries can lead to diarrhea due to intentional or inadvertent

vagotomy, small intestinal bacterial overgrowth, and based on the length of small bowel
resection, bile acid malabsorption, or short bowel syndrome. (See "Approach to the adult
patient with suspected malabsorption" and "Overview of the treatment of malabsorption in
adults" and "Pathophysiology of short bowel syndrome", section on 'Initial determinants of
intestinal function' and "Small intestinal bacterial overgrowth: Clinical manifestations and
diagnosis".)
-Diarrhea in patients with diabetes may also be due to visceral autonomic neuropathy,
pancreatic exocrine insufficiency, bacterial overgrowth, or fecal incontinence (which may be
confused with diarrhea). (See "Diabetic autonomic neuropathy of the gastrointestinal tract".)
•Family history of colorectal cancer, celiac disease and inflammatory bowel disease (IBD)are
associated with an increased risk of these disorders. (See "Diagnosis of celiac disease in
adults", section on 'Individuals with high celiac disease probability' and "Genetic factors in
inflammatory bowel disease".)
Physical examination — A comprehensive physical examination should be

performed that includes a dermatologic examination and rectal examination. Physical
examination rarely provides a specific diagnosis. However, a number of findings can provide
clues (table 7).
General laboratory tests — We suggest the following initial tests for most
patients with chronic diarrhea (table 7):
●Complete blood count and differential.
●Thyroid stimulating hormone and free thyroxine (T4) to identify patients with
hyperthyroidism.
●Celiac serologies (see "Diagnosis of celiac disease in adults", section on 'Overview').
●Serum electrolytes in patients with severe diarrhea, or concern for dehydration or

electrolyte abnormalities.
●Stool occult blood – Gross or occult gastrointestinal bleeding is suggestive of organic

disease (eg, chronic infection or IBD).
●Stool test for giardia – Giardia stool antigen and nucleic acid detection tests are more
sensitive for the diagnosis of giardiasis as compared to stool microscopy. (See "Giardiasis:
Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)
●Fecal calprotectin or fecal lactoferrin – Fecal calprotectin levels are increased in intestinal
inflammation and may be useful for distinguishing inflammatory from noninflammatory
causes of chronic diarrhea [38,39]. Calprotectin is a zinc and calcium binding protein that is
derived mostly from neutrophils and monocytes. It can be detected in tissue samples, body
fluids, and stools, making it a potentially valuable marker of neutrophil activity [40]. The
fecal lactoferrin test is an agglutination assay that is a marker for fecal leukocytes [41].
If fecal calprotectin and fecal lactoferrin are normal, a diagnosis of IBD is unlikely. If fecal
calprotectin or fecal lactoferrin levels are above the reference range, we proceed with
ileocolonoscopy and biopsy to confirm the diagnosis of IBD. (See 'Patients with alarm
features' below and 'Inflammatory bowel disease' above.)
●C-reactive protein – C-reactive protein levels have limited utility in differentiating IBS and
IBD and should be performed in the evaluation of patients with chronic diarrhea if fecal
calprotectin and fecal lactoferrin cannot be performed [42].
Additional laboratory evaluation may be warranted if specific organic conditions are

suspected:
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•Stool microbiologic evaluation – Patients with recent antibiotic therapy or suspected

Clostridioides difficile infection should undergo testing for C. difficile associated diarrhea.
(See "Clostridioides difficile infection in adults: Clinical manifestations and diagnosis",
section on 'When to suspect and test for C. difficile infection'.)
Additional testing may also be indicated based on other risk factors for infectious diarrhea.
Persistent diarrhea following travel to certain locations, such as Russia, Nepal, or
mountainous regions, is associated with Giardia, Cryptosporidium, or Cyclospora. Persistent
diarrhea with exposure to infants in daycare centers has been associated with Giardia and
Cryptosporidium. Microsporidium should be a consideration in immunocompromised
patients with persistent diarrhea. (See "Approach to the adult with acute diarrhea in
resource-rich settings", section on 'Persistent diarrhea' and "Giardiasis: Epidemiology,
clinical manifestations, and diagnosis", section on 'Diagnosis' and "Cryptosporidiosis:
Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and
"Cyclospora infection", section on 'Diagnosis' and "Microsporidiosis", section on 'Diagnosis'
and "Clostridioides difficile infection in adults: Clinical manifestations and diagnosis",
section on 'Diagnosis'.)
•Fecal leukocytes – Fecal leukocyte evaluation is not an accurate test for inflammatory
diarrhea [43]. A number of studies have evaluated the accuracy of fecal leukocytes alone or
in combination with occult blood testing. The ability of these tests to predict the presence of
an inflammatory diarrhea has varied greatly, with reports of sensitivity and specificity
ranging from 20 to 90 percent [44-47]. A meta-analysis of diagnostic test accuracy estimated
that at a peak sensitivity of 70 percent, the specificity of fecal leukocytes was only 50
percent [47].
ESTABLISHING A DIAGNOSIS
Patients with alarm features — Patients with alarm findings require
endoscopic evaluation for organic disorders. Patients with abdominal pain as a major
symptom in addition to chronic diarrhea often require abdominal imaging (table 2). (See
'Imaging in selected patients' below and 'Endoscopic evaluation' below.)
If an etiology is established, patients should be managed based on the underlying cause. If

an etiology is not identified, additional evaluation should be guided by the initial evaluation
similar to patients without alarm features. (See 'Treatment of the underlying etiology' below
and 'Patients without alarm features' below.)
Patients without alarm features

Specific diagnosis suspected — If the initial evaluation points

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specific diagnosis or type of diarrhea, further testing should be directed toward confirming
the diagnosis. As examples, upper endoscopy with duodenal biopsies can establish the
diagnosis of celiac disease in a patient with positive celiac serologies; breath test for
bacterial overgrowth in a patient with risk factors; in a patient with suspected inflammatory
bowel disease (IBD) due to a family history of IBD, the diagnosis can usually be established
by colonoscopy. (See 'Initial evaluation' above and "Small intestinal bacterial overgrowth:
Clinical manifestations and diagnosis", section on 'Etiology and risk factors'.)
Further testing in patients with osmotic diarrhea may be unnecessary if the osmotic agent
can be identified based upon the history. An example is inadvertent ingestion of sorbitol
(such as in sugar substitutes) or lactose in patients who have lactose intolerance. Temporary
avoidance of lactose-containing foods can help establish the diagnosis of lactose
intolerance in patients who were unaware of the diagnosis. (See "Small intestinal bacterial
overgrowth: Clinical manifestations and diagnosis", section on 'Diagnosis' and "Lactose
intolerance and malabsorption: Clinical manifestations, diagnosis, and management",
section on 'Management'.)
In other cases, empiric therapy may be indicated (eg, cholestyramine for bile acid
malabsorption in a patient with a history of ileal resection). (See 'Empiric therapy in selected
patients' below.)
Functional bowel disease suspected — A clinical diagnosis of irritable

bowel syndrome (IBS) or functional diarrhea requires the fulfillment of symptom-based
diagnostic criteria and a limited initial evaluation to exclude underlying organic disease. In
patients with IBS, these include presence of recurrent abdominal pain at least three days
per month in the last three months, associated with a change in stool frequency or form,
and improvement with defecation. Functional diarrhea is defined as similar stool changes
without prominent pain. (See 'Initial evaluation' above and 'Functional disorders' above and
"Clinical manifestations and diagnosis of irritable bowel syndrome in adults", section on
'Diagnosis'.)
However, the presence of persistent symptoms despite treatment, atypical symptoms (eg,
older age of onset), or progressive symptoms require additional evaluation for alternative
etiologies. (See 'Additional testing in specific circumstances' below.)
Unclear diagnosis after initial evaluation — If the initial evaluation

does not point toward a specific diagnosis, we perform additional testing. (See 'Overview'
above and 'Additional testing in specific circumstances' below.)
ADDITIONAL TESTING IN SPECIFIC Your activity: 21 p.v.

CIRCUMSTANCES — For patients with persistent diarrhea with no clear
etiology after initial evaluation or diarrhea that does not respond to initial treatment, we
perform additional testing to determine the underlying etiology. The order and extent of
testing should be individualized based on the clinical presentation and results of initial
evaluation. (See 'Initial evaluation' above.)
Laboratory evaluation
●Blood tests for malabsorption – An initial screen for nutritional deficits can provide
indirect evidence of malabsorption. This includes a complete blood count, red cell folate and
serum iron, total iron binding capacity, vitamin B12, calcium, magnesium, albumin,
carotene, and 25-hydroxyvitamin D. Blood tests can provide supportive evidence of
malabsorption. Clinical or laboratory features suggesting malabsorption should prompt a
specific evaluation (table 3 and table 4). (See "Approach to the adult patient with suspected
malabsorption".)
●Stool tests – Work-up for patients with persistent diarrhea should include evaluation for C.
difficile and parasitic infections (eg, Giardia, Cryptosporidium, Cyclospora, E. histolytica), if
not already performed. Microsporidium should be a consideration in immunocompromised
patients with persistent diarrhea. (See 'General laboratory tests' above and "Approach to the
adult with acute diarrhea in resource-rich settings", section on 'Persistent diarrhea' and
"Approach to the adult with acute diarrhea in resource-rich settings", section on
'Immunocompromised patients'.)
Endoscopic evaluation — We generally perform colonoscopy and obtain

mucosal biopsies in patients with chronic diarrhea, if not previously performed.
Colonoscopy has the advantage of allowing evaluation of the terminal ileum and sampling
of the right and left colon. Flexible sigmoidoscopy (to 60 cm) is less expensive, is associated
with fewer risks as compared with colonoscopy and may be appropriate for selected
patients [48-51]. However, colonoscopy should be performed in patients with iron deficiency
anemia, those in whom inspection of the terminal ileum is needed (eg, to exclude Crohn
disease), patients who require age appropriate screening for colorectal cancer, and those
with suspected microscopic colitis. (See "Microscopic (lymphocytic and collagenous) colitis:
Clinical manifestations, diagnosis, and management", section on 'Endoscopy and biopsy'.)
In patients with positive serologic testing for celiac disease and in patients at increased risk
for celiac disease (regardless of celiac specific serology results), an upper endoscopy with
small bowel biopsy should be performed. (See "Diagnosis of celiac disease in adults",
section on 'Overview'.)
Imaging in selected patients — In patients with abdominal pain as21

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major symptom, systemic symptoms (fever, weight loss), or suspected Crohn or pancreatic
disease based on history, we perform additional abdominal imaging with an abdominal
computed tomography (CT) or magnetic resonance imaging (MRI). In patients with
suspected chronic pancreatitis, we perform a magnetic resonance
cholangiopancreatography. An MRE (magnetic resonance enterography) can be used to
identify small bowel Crohn disease or small bowel tumors. (See "Clinical manifestations,
diagnosis, and prognosis of Crohn disease in adults", section on 'Imaging'.)
Plain abdominal films have limited utility in the evaluation of chronic diarrhea. Supine and
upright position can provide evidence of bowel distention or air-fluid levels suggesting a
motility disease, megacolon due to infectious or inflammatory processes, or partial
mechanical obstruction due to strictures in Crohn disease or tumors such as carcinoid.
Tests to evaluate uncommon causes — Additional testing for

uncommon disorders may be appropriate in the subset of patients with persistent
symptoms in whom a diagnosis remains unclear (table 2).
●We perform an upper endoscopy with mucosal biopsies, if not previously performed, to
rule out small bowel enteropathies.
●We reserve laboratory testing for hormone secreting tumors (eg, fasting serum gastrin,
calcitonin, somatostatin, vasoactive intestinal polypeptide, 24-hour urine 5-HIAA) in patients
where no other etiology if found (algorithm 1). (See "Zollinger-Ellison syndrome
(gastrinoma): Clinical manifestations and diagnosis" and "VIPoma: Clinical manifestations,
diagnosis, and management".)
●Testing for laxatives may occasionally be required if laxative abuse is suspected based on
history or endoscopic evaluation (presence of melanosis coli). A screen for laxative abuse
should include the detection of anthraquinones, bisacodyl and phenolphthalein in urine and
magnesium and phosphate in stool. (See "Factitious diarrhea: Clinical manifestations,
diagnosis, and management", section on 'Diagnosis'.)
MANAGEMENT
Treatment of the underlying etiology — Specific therapy should
be directed to the underlying etiology in patients in whom the diagnosis has been
established. The management of specific disorders associated with chronic diarrhea are
presented in detail separately in the corresponding topic reviews.
Empiric therapy in selected patients — Empiric therapy may be

appropriate when comorbidities limit diagnostic evaluation or when a diagnosis is strongly
suspected. Examples include:
•Empiric antibiotics for small intestinal bacterial overgrowth (SIBO) in patients with
recurrent SIBO and predisposing risk factors. (See "Small intestinal bacterial overgrowth:
Management", section on 'Inadequate response to initial therapy or recurrence'.)
•Lactose restriction in a patient with suspected lactose intolerance in whom relief of

symptoms is observed following a temporary trial of a lactose-free diet. (See "Lactose
intolerance and malabsorption: Clinical manifestations, diagnosis, and management",
section on 'Dietary lactose restriction'.)
•Cholestyramine for bile acid diarrhea in a patient who develops diarrhea following limited
(<100 cm) ileal resection, abdominal radiation therapy, or post-cholecystectomy diarrhea
[16,22]. It is reasonable to start patients on a low dose (eg, 2 g once or twice daily) and
titrate to a higher dose as needed. We have found that patients often prefer pill
formulations (ie, colestipol) over the powder (ie, cholestyramine). (See "Overview of the
treatment of malabsorption in adults", section on 'Directed therapy based on the underlying
etiology'.)
Symptomatic therapy — Symptomatic therapy to reduce the frequency and

severity of chronic diarrhea is indicated when the diagnosis has been made but definitive
treatment is unavailable, when diagnosis has eluded diagnostic evaluation, and as a
temporizing measure during evaluation. A variety of medications can help relieve diarrhea
including loperamide, anticholinergic agents, and intraluminal adsorbents (such as clays,
activated charcoal, bismuth, fiber and bile acid binding resins). Symptomatic therapy may
also be used to manage diarrhea in specific disorders and is discussed in the corresponding
topic reviews.
SOCIETY GUIDELINE LINKS — Links to society and government-

sponsored guidelines from selected countries and regions around the world are provided
separately. (See "Society guideline links: Chronic diarrhea".)
INFORMATION FOR PATIENTS — UpToDate offers two types

of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient
education pieces are written in plain language, at the 5th to 6th grade reading level, and they
answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated,
and more detailed. These articles are written at the 10th to 12th grade reading level and are
best for patients who want in-depth information and are comfortable with some medical
jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Chronic diarrhea in adults (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS

●Etiology – Chronic diarrhea is defined as a persistent alteration of stool consistency from
the norm with loose stools (consistency between types 5 and 7 on the Bristol stool chart)
and increased stool frequency of greater than four weeks' duration. In resource-abundant
settings the most prevalent causes are irritable bowel syndrome, inflammatory bowel
disease (IBD), malabsorption syndromes (such as lactose intolerance and celiac disease),
and chronic infections (particularly in patients who are immunocompromised) (table 1). (See
'Etiology' above.)
●Indications for gastroenterology referral – The need for gastroenterology evaluation

and timing of referral for chronic diarrhea depend upon the severity of symptoms, the
diagnoses being considered, and the presence of alarm features (table 2). (See 'Indications
for referral to a gastroenterologist' above.)
Indications for referral include anyone of the following:
•Alarm features (table 2)
•Severe diarrhea
•Suspected inflammatory bowel disease (see 'Inflammatory bowel disease' above)
•Inconclusive diagnosis after initial evaluation (see 'Initial evaluation' above and
'Establishing a diagnosis' above)
•Failure to respond to empiric therapy (see 'Empiric therapy in selected patients' above)
Referral to a gastroenterologist may also be appropriate in patients who require long-term

management for the underlying cause (eg, IBD, chronic pancreatitis).
●Initial evaluation – The initial evaluation of patient with chronic diarrhea includes history,
physical examination, and laboratory testing to determine whether the patient has any
alarm features which help to distinguish organic from functional diarrhea and
characterizing the diarrhea (infectious, inflammatory, osmotic, secretory) in order to direct
evaluation (algorithm 1). (See 'Overview' above and 'History' above and 'Physical
examination' above and 'General laboratory tests' above.)
●Additional evaluation based on the presence of alarm features
•Patients with alarm features – Patients with alarm features require endoscopic
evaluation for organic disorders. Patients with abdominal pain as a major symptom in
addition to chronic diarrhea often require abdominal imaging. (See 'Endoscopic evaluation'
above and 'Imaging in selected patients' above.)
•Patients without alarm features – In patients without alarm features, if the initial
evaluation points toward a specific diagnosis or type of diarrhea, further testing should be
directed toward confirming the diagnosis. However, in some cases, further testing may be
unnecessary (eg, functional diarrhea or suspected lactose intolerance) and patients can be
managed empirically (lactose restriction for lactose intolerance, cholestyramine for post-
cholecystectomy diarrhea). (See 'Patients without alarm features' above.)
●Patients with persistent symptoms – In patients with persistent diarrhea with no clear
etiology after initial evaluation or diarrhea that does not respond to initial treatment, we
perform additional testing to determine the underlying etiology. This evaluation is
individualized based on the clinical presentation and can include screening for evidence of
malabsorption, stool tests for evidence of an infection, and endoscopic evaluation if not
previously performed. We perform imaging (abdominal computed tomography or magnetic
resonance imaging) in patients with unexplained diarrhea and abdominal pain as a major
symptom, systemic symptoms (fever, weight loss), or suspected Crohn or pancreatic disease
based on history. (See 'Additional testing in specific circumstances' above.)
ACKNOWLEDGMENT — We are saddened by the death of Paul Rutgeerts, MD, who passed
away in September 2020. UpToDate gratefully acknowledges Dr. Rutgeerts' work as our
Section Editor for Gastroenterology.
1. Peery AF, Crockett SD, Murphy CC, et al. Burden and Cost of Gastrointestinal, Liver, and
Pancreatic Diseases in the United States: Update 2018. Gastroenterology 2019; 156:254.
2. Dutra B, Siddiqui S, Everett J. A Clinical Approach to Chronic Diarrhea. Gastroenterology
2022; 162:707.
3. Arasaradnam RP, Brown S, Forbes A, et al. Guidelines for the investigation of chronic
diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut 2018; 67:1380.
4. Schiller LR, Pardi DS, Spiller R, et al. Gastro 2013 APDW/WCOG Shanghai working party
report: chronic diarrhea: definition, classification, diagnosis. J Gastroenterol Hepatol
2014; 29:6.
5. Blake MR, Raker JM, Whelan K. Validity and reliability of the Bristol Stool Form Scale in
healthy adults and patients with diarrhoea-predominant irritable bowel syndrome.
Aliment Pharmacol Ther 2016; 44:693.
6. Gómez-Escudero O, Remes-Troche JM. Approach to the adult patient with chronic
diarrhea: A literature review. Rev Gastroenterol Mex (Engl Ed) 2021; 86:387.
7. Gómez-Escudero O, Remes-Troche JM. Approach to the adult patient with chronic
diarrhea: a literature review. Rev Gastroenterol Mex (Engl Ed) 2021.
8. Schiller LR, Pardi DS, Sellin JH. Chronic Diarrhea: Diagnosis and Management. Clin
Gastroenterol Hepatol 2017; 15:182.
9. Singh P, Mitsuhashi S, Ballou S, et al. Demographic and Dietary Associations of Chronic
Diarrhea in a Representative Sample of Adults in the United States. Am J Gastroenterol
2018; 113:593.
10. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States part II: lower
gastrointestinal diseases. Gastroenterology 2009; 136:741.
11. Peery AF, Crockett SD, Barritt AS, et al. Burden of Gastrointestinal, Liver, and Pancreatic
Diseases in the United States. Gastroenterology 2015; 149:1731.
12. Ma C, Congly SE, Novak KL, et al. Epidemiologic Burden and Treatment of Chronic
Symptomatic Functional Bowel Disorders in the United States: A Nationwide Analysis.
Gastroenterology 2021; 160:88.
13. Berumen A, Edwinson AL, Grover M. Post-infection Irritable Bowel Syndrome.
Gastroenterol Clin North Am 2021; 50:445.
14. Schmulson MJ, Drossman DA. What Is New in Rome IV. J Neurogastroenterol Motil 2017;
23:151.
15. Lacy BE, Pimentel M, Brenner DM, et al. ACG Clinical Guideline: Management of Irritable
Bowel Syndrome. Am J Gastroenterol 2021; 116:17.
16. Costa S, Gattoni S, Nicolardi ML, et al. Prevalence and clinical features of bile acid
diarrhea in patients with chronic diarrhea. J Dig Dis 2021; 22:108.
17. Farrugia A, Attard JA, Hanmer S, et al. Rates of Bile Acid Diarrhoea After
Cholecystectomy: A Multicentre Audit. World J Surg 2021; 45:2447.
18. Camilleri M, Nurko S. Bile Acid Diarrhea in Adults and Adolescents. Neurogastroenterol
Motil 2022; 34:e14287.
19. Sauter GH, Moussavian AC, Meyer G, et al. Bowel habits and bile acid malabsorption in
the months after cholecystectomy. Am J Gastroenterol 2002; 97:1732.
20. Arlow FL, Dekovich AA, Priest RJ, Beher WT. Bile acid-mediated postcholecystectomy
diarrhea. Arch Intern Med 1987; 147:1327.
21. Breuer NF, Jaekel S, Dommes P, Goebell H. Fecal bile acid excretion pattern in
cholecystectomized patients. Dig Dis Sci 1986; 31:953.
22. Sadowski DC, Camilleri M, Chey WD, et al. Canadian Association of Gastroenterology
Clinical Practice Guideline on the Management of Bile Acid Diarrhea. Clin Gastroenterol
Hepatol 2020; 18:24.
23. Schiller LR. Good News about BAD. Clin Gastroenterol Hepatol 2020; 18:45.
24. Lo Vecchio A, Conelli ML, Guarino A. Infections and Chronic Diarrhea in Children.
Pediatr Infect Dis J 2021; 40:e255.
25. Bryant DA, Mintz ED, Puhr ND, et al. Colonic epithelial lymphocytosis associated with an
epidemic of chronic diarrhea. Am J Surg Pathol 1996; 20:1102.
26. Janda RC, Conklin JL, Mitros FA, Parsonnet J. Multifocal colitis associated with an
epidemic of chronic diarrhea. Gastroenterology 1991; 100:458.
27. Mintz ED, Weber JT, Guris D, et al. An outbreak of Brainerd diarrhea among travelers to
the Galapagos Islands. J Infect Dis 1998; 177:1041.
28. Osterholm MT, MacDonald KL, White KE, et al. An outbreak of a newly recognized
chronic diarrhea syndrome associated with raw milk consumption. JAMA 1986; 256:484.
29. Vugia DJ, Abbott S, Mintz ED, et al. A restaurant-associated outbreak of Brainerd
diarrhea in California. Clin Infect Dis 2006; 43:62.
30. Kimura AC, Mead P, Walsh B, et al. A large outbreak of Brainerd diarrhea associated with
a restaurant in the Red River Valley, Texas. Clin Infect Dis 2006; 43:55.
31. Hellmig S, Ott S, Musfeldt M, et al. Life-threatening chronic enteritis due to colonization
of the small bowel with Stenotrophomonas maltophilia. Gastroenterology 2005;
129:706.
32. Friedman M, Ramsay DB, Borum ML. An unusual case report of small bowel Candida
overgrowth as a cause of diarrhea and review of the literature. Dig Dis Sci 2007; 52:679.
33. Philip NA, Ahmed N, Pitchumoni CS. Spectrum of Drug-induced Chronic Diarrhea. J Clin
Gastroenterol 2017; 51:111.
34. Burbure N, Lebwohl B, Arguelles-Grande C, et al. Olmesartan-associated sprue-like
enteropathy: a systematic review with emphasis on histopathology. Hum Pathol 2016;
50:127.
35. Kroschinsky F, Stölzel F, von Bonin S, et al. New drugs, new toxicities: severe side effects
of modern targeted and immunotherapy of cancer and their management. Crit Care
2017; 21:89.
36. Mauloni PA, Capuani F, Paone C, et al. An unusual cause of diarrhoea: case report and
literature review of olmesartan-associated enteropathy. Eur J Gastroenterol Hepatol
2021; 33:e1060.
37. Sotiropoulos C, Sakka E, Diamantopoulou G, et al. Olmesartan-Induced Enteropathy: A
Report of an Unusual Cause of Chronic Diarrhea. Cureus 2021; 13:e17004.
38. Holtman GA, Lisman-van Leeuwen Y, Reitsma JB, Berger MY. Noninvasive Tests for
Inflammatory Bowel Disease: A Meta-analysis. Pediatrics 2016; 137.
39. Mosli MH, Zou G, Garg SK, et al. C-Reactive Protein, Fecal Calprotectin, and Stool
Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel
Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2015;
110:802.
40. Poullis A, Foster R, Mendall MA, Fagerhol MK. Emerging role of calprotectin in
gastroenterology. J Gastroenterol Hepatol 2003; 18:756.
41. Kane SV, Sandborn WJ, Rufo PA, et al. Fecal lactoferrin is a sensitive and specific marker
in identifying intestinal inflammation. Am J Gastroenterol 2003; 98:1309.
42. Smalley W, Falck-Ytter C, Carrasco-Labra A, et al. AGA Clinical Practice Guidelines on the
Laboratory Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel
Syndrome in Adults (IBS-D). Gastroenterology 2019; 157:851.
43. Schoepfer AM, Trummler M, Seeholzer P, et al. Accuracy of four fecal assays in the
diagnosis of colitis. Dis Colon Rectum 2007; 50:1697.
44. Chitkara YK, McCasland KA, Kenefic L. Development and implementation of cost-
effective guidelines in the laboratory investigation of diarrhea in a community hospital.
Arch Intern Med 1996; 156:1445.
45. Stoll BJ, Glass RI, Banu H, et al. Value of stool examination in patients with diarrhoea. Br
Med J (Clin Res Ed) 1983; 286:2037.
46. Siegel D, Cohen PT, Neighbor M, et al. Predictive value of stool examination in acute
diarrhea. Arch Pathol Lab Med 1987; 111:715.
47. Huicho L, Sanchez D, Contreras M, et al. Occult blood and fecal leukocytes as screening
tests in childhood infectious diarrhea: an old problem revisited. Pediatr Infect Dis J
1993; 12:474.
48. Ferren LG, Ward RL, Campbell BJ. Monoanion inhibition and 35Cl nuclear magnetic
resonance studies of renal dipeptidase. Biochemistry 1975; 14:5280.
49. Hodgson EK, Fridovich I. The interaction of bovine erythrocyte superoxide dismutase
with hydrogen peroxide: inactivation of the enzyme. Biochemistry 1975; 14:5294.
50. Jaton JC, Huser H, Blatt Y, Pecht I. Circular dichroism and fluorescence studies of
homogeneous antibodies to type III pneumococcal polysaccharide. Biochemistry 1975;
14:5308.
51. Jaton JC, Huser H, Braun DG, et al. Conformational changes induced in a homogeneous
anti-type III pneumococcal antibody by oligosaccharides of increasing size.
Biochemistry 1975; 14:5312.
Topic 2591 Version 39.0
References
1 : Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States:
Update 2018.
2 : A Clinical Approach to Chronic Diarrhea.
3 : Guidelines for the investigation of chronic diarrhoea in adults: British Society of
Gastroenterology, 3rd edition.

4 : Gastro 2013 APDW/WCOG Shanghai working party report: chronic diarrhea: definition,
classification, diagnosis.
5 : Validity and reliability of the Bristol Stool Form Scale in healthy adults and patients with
diarrhoea-predominant irritable bowel syndrome.
6 : Approach to the adult patient with chronic diarrhea: A literature review.
7 : Approach to the adult patient with chronic diarrhea: a literature review.
8 : Chronic Diarrhea: Diagnosis and Management.
9 : Demographic and Dietary Associations of Chronic Diarrhea in a Representative Sample of

Adults in the United States.
10 : Burden of digestive diseases in the United States part II: lower gastrointestinal diseases.
11 : Burden of Gastrointestinal, Liver, and Pancreatic Diseases in the United States.
12 : Epidemiologic Burden and Treatment of Chronic Symptomatic Functional Bowel Disorders

in the United States: A Nationwide Analysis.
13 : Post-infection Irritable Bowel Syndrome.
14 : What Is New in Rome IV.
15 : ACG Clinical Guideline: Management of Irritable Bowel Syndrome.
16 : Prevalence and clinical features of bile acid diarrhea in patients with chronic diarrhea.
17 : Rates of Bile Acid Diarrhoea After Cholecystectomy: A Multicentre Audit.
18 : Bile Acid Diarrhea in Adults and Adolescents.
19 : Bowel habits and bile acid malabsorption in the months after cholecystectomy.
20 : Bile acid-mediated postcholecystectomy diarrhea.
21 : Fecal bile acid excretion pattern in cholecystectomized patients. Your activity: 21 p.v.
22 : Canadian Association of Gastroenterology Clinical Practice Guideline on the Management

of Bile Acid Diarrhea.
23 : Good News about BAD.
24 : Infections and Chronic Diarrhea in Children.
25 : Colonic epithelial lymphocytosis associated with an epidemic of chronic diarrhea.
26 : Multifocal colitis associated with an epidemic of chronic diarrhea.
27 : An outbreak of Brainerd diarrhea among travelers to the Galapagos Islands.
28 : An outbreak of a newly recognized chronic diarrhea syndrome associated with raw milk
consumption.
29 : A restaurant-associated outbreak of Brainerd diarrhea in California.
30 : A large outbreak of Brainerd diarrhea associated with a restaurant in the Red River Valley,
Texas.
31 : Life-threatening chronic enteritis due to colonization of the small bowel with

Stenotrophomonas maltophilia.
32 : An unusual case report of small bowel Candida overgrowth as a cause of diarrhea and
review of the literature.
33 : Spectrum of Drug-induced Chronic Diarrhea.
34 : Olmesartan-associated sprue-like enteropathy: a systematic review with emphasis on

histopathology.
35 : New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of
cancer and their management.
36 : An unusual cause of diarrhoea: case report and literature review of olmesartan-associated

enteropathy.
YourDiarrhea.
37 : Olmesartan-Induced Enteropathy: A Report of an Unusual Cause of Chronic activity: 21 p.v.
38 : Noninvasive Tests for Inflammatory Bowel Disease: A Meta-analysis.
39 : C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic
Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-
Analysis.
40 : Emerging role of calprotectin in gastroenterology.
41 : Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation.
42 : AGA Clinical Practice Guidelines on the Laboratory Evaluation of Functional Diarrhea and
Diarrhea-Predominant Irritable Bowel Syndrome in Adults (IBS-D).
43 : Accuracy of four fecal assays in the diagnosis of colitis.
44 : Development and implementation of cost-effective guidelines in the laboratory

investigation of diarrhea in a community hospital.
45 : Value of stool examination in patients with diarrhoea.
46 : Predictive value of stool examination in acute diarrhea.
47 : Occult blood and fecal leukocytes as screening tests in childhood infectious diarrhea: an
old problem revisited.
48 : Monoanion inhibition and 35Cl nuclear magnetic resonance studies of renal dipeptidase.
49 : The interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide:

inactivation of the enzyme.
50 : Circular dichroism and fluorescence studies of homogeneous antibodies to type III

pneumococcal polysaccharide.
51 : Conformational changes induced in a homogeneous anti-type III pneumococcal antibody

by oligosaccharides of increasing size.

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3/19/23, 10:21 AM Approach to the adult with chronic diarrhea in resource-abundant settings - Uptodate Free

Your activity: 21 p.v.

Approach to the adult with chronic diarrhea

INTRODUCTION — Diarrhea is a common manifestation of gastrointestinal

DEFINITION — Chronic diarrhea is defined as a persistent alteration of stool

EPIDEMIOLOGY — The prevalence of chronic diarrhea in the general

ETIOLOGY — The principal causes of diarrhea vary based upon the

Functional disorders — Patients with IBS complain of cramping

Organic disorders — Organic disorders are conditions that are associated with

Inflammatory bowel disease — Inflammatory bowel disease (IBD) primarily

Microscopic colitis — Microscopic colitis usually occurs in middle-aged and older

Colonoscopy usually reveals macroscopically normal colonic mucosa, although slight

Malabsorption syndromes — The classic manifestations of malabsorption

Relatively common disorders associated with malabsorption include:

●Lactose intolerance (see "Lactose intolerance and malabsorption: Clinical manifestations,

●Chronic pancreatitis (see "Chronic pancreatitis: Clinical manifestations and diagnosis in

●Celiac disease (see "Epidemiology, pathogenesis, and clinical manifestations of celiac

Post-cholecystectomy diarrhea — The incidence of diarrhea following

Chronic infections — Some persisting infections (eg, C. difficile, Aeromonas,

diarrhea that was ultimately found to be due to Stenotrophomonas maltophilia, a Gram-

Medications — Many drugs can cause diarrhea through a variety of mechanisms [33-

INDICATIONS FOR REFERRAL TO A

Indications for referral include anyone of the following:

•Suspected inflammatory bowel disease (see 'Inflammatory bowel disease' above)

Referral to a gastroenterologist may also be appropriate in patients who require long-term

Evaluation for alarm features — Alarm features in patients with chronic

•Age of onset after age 50 years

•Rectal bleeding or melena [6]

•Nocturnal pain or diarrhea

•Progressive abdominal pain

•Unexplained weight loss, fever, or other systemic symptoms

•Laboratory abnormalities (iron deficiency anemia, elevated C-reactive protein or fecal

•Family history of inflammatory bowel disease (IBD) or colorectal cancer

Characterizing the diarrhea type — Information other than alarm

•Osmotic – Osmotic (or "substrate-induced" or "diet-related") diarrhea typically is less

●Fatty diarrhea – Malabsorption is often accompanied by steatorrhea and the passage of

●Inflammatory diarrhea – Inflammatory forms of diarrhea typically present with liquid

•Duration of symptoms, nature of onset (sudden or gradual).

•Occurrence of diarrhea during fasting or at night suggests a secretory or inflammatory

•All medications (including over-the-counter drugs and supplements) (table 5) [2].

-A history of or risk factors for sexually transmitted diseases. As examples, Neisseria

-A history of chronic diseases associated with amyloidosis (eg, chronic degenerative

-Prior gastrointestinal surgeries can lead to diarrhea due to intentional or inadvertent

Physical examination — A comprehensive physical examination should be

●Complete blood count and differential.

●Celiac serologies (see "Diagnosis of celiac disease in adults", section on 'Overview').

●Serum electrolytes in patients with severe diarrhea, or concern for dehydration or

●Stool occult blood – Gross or occult gastrointestinal bleeding is suggestive of organic

Additional laboratory evaluation may be warranted if specific organic conditions are

Other tests Your activity: 21 p.v.

•Stool microbiologic evaluation – Patients with recent antibiotic therapy or suspected

If an etiology is established, patients should be managed based on the underlying cause. If

Patients without alarm features

Specific diagnosis suspected — If the initial evaluation points

Functional bowel disease suspected — A clinical diagnosis of irritable

Unclear diagnosis after initial evaluation — If the initial evaluation

ADDITIONAL TESTING IN SPECIFIC Your activity: 21 p.v.

Endoscopic evaluation — We generally perform colonoscopy and obtain

Imaging in selected patients — In patients with abdominal pain as21

Tests to evaluate uncommon causes — Additional testing for

Empiric therapy in selected patients — Empiric therapy may be

•Lactose restriction in a patient with suspected lactose intolerance in whom relief of

Symptomatic therapy — Symptomatic therapy to reduce the frequency and