Intern Emerg Med (2012) 7 (Suppl 3):S255S262

DOI 10.1007/s11739-012-0827-4

SELECTED PAPER CHRONIC DIARRHOEA

Clinical approach to diarrhea

Roberto Corinaldesi Vincenzo Stanghellini

Giovanni Barbara Paola Tomassetti

Roberto De Giorgio

SIMI 2012

Abstract Diarrhea is defined as reduced stool consis- clinical features are expected to reduce costs for patients
tency, increased water content and number of evacuations with chronic diarrhea.
per day. A wide array of causes and pathophysiological
mechanisms underlie acute and chronic forms of diarrhea. Keywords Chronic diarrhea
Osmotic diarrhea

This review focuses on the major clinical aspects which Secretory diarrhea
Steatorrhea
should aid clinicians to diagnose chronic diarrhea. Clinical
history, physical examination and stool evaluation and the Abbreviations
predominant stool characteristic, i.e., bloody, watery, and EMA Endomysial antibodies
fatty diarrhea, may narrow the differential diagnosis. FD Functional diarrhea
Although mainly involved in acute diarrhea, many different IBD Inflammatory bowel disease
infectious agents, including bacteria, viruses and protozoa, IBS Irritable bowel syndrome
can be identified in chronic bloody/inflammatory diarrhea IBS-C Constipation predominant irritable bowel
by appropriate microbiological tests and colonoscopic syndrome
biopsy analysis. Osmotic diarrhea can be the result of IBS-D Diarrhea predominant irritable bowel
malabsorption or maldigestion, with a subsequent passage syndrome
of fat in the stool leading to steatorrhea. Secretory diarrhea MRI Magnetic resonance imaging
75
is due to an increase of fluid secretion in the small bowel SeHCAT 75-Seleniumhomotaurocholic acid
lumen, a mechanism often identified in gastroenteropan- tTG Tissue transglutaminase
creatic neuroendocrine tumors. The evaluation of the fecal VIP Vasoactive intestinal polypeptide
osmotic gap may help to characterize whether a chronic
diarrhea is osmotic or secretory. Fatty diarrhea (steator-
rhea) occurs if fecal fat output exceeds the absorptive/
digestive capacity of the intestine. Steatorrhea results from General features of diarrhea
malabsorption or maldigestion states and tests should dif-
ferentiate between these two conditions. Individualized Diarrhea (a term derived from the ancient Greek words dia,
diagnostic work ups tailored on pathophysiological and through and qeim, to go or to flow) is one of the most
common complaints reported by patients seen in primary
care up to tertiary referral centers. It is the cause of relevant
morbidity and social costs in developed countries and one
R. Corinaldesi (&)
V. Stanghellini
G. Barbara

of the most frequent causes of mortality particularly in the
P. Tomassetti
R. De Giorgio pediatric population in developing countries. Overall,
Department of Clinical Medicine, Digestive Diseases diarrhea is characterized by a reduced stool consistency (or
and Internal Medicine, University of Bologna, loose stools) essentially due to an incomplete absorption
St. Orsola-Malpighi Hospital, Bldg #5, Nuove Patologie,
Via Massarenti 9, 40138 Bologna, Italy
of water and electrolyte by the intestine [1, 2]. This is the
e-mail: roberto.corinaldesi@unibo.it result of an altered electrolyte absorption/secretion or

123
S256
non-absorbable/osmotically active substances introduced
with foods, which accumulate in the intestinal lumen.
Understanding the ending balance of fluids, i.e., the oral
intake in addition to gastrointestinal secretions versus the
amount that is adsorbed, is of crucial importance as it bears
major implications for the complex pathophysiological
mechanisms underlying most forms of diarrhea.
A detailed analysis of physiological mechanisms of
daily fluid fluxes throughout the gastrointestinal tract is
beyond the purpose of the present review. Nonetheless, a
brief account of intestinal fluid absorption/secretion in
physiological condition is relevant to the categorization of
diarrhea and therefore of its clinical approach. Studies have
established that the daily amount of fluid flowing through
the small bowel is about 78 L. This fluid includes oral
intake and saliva (1.5 L), gastric acid secretion and pepsin
(1.5 L), bile and pancreatic secretions (1 L each) and
enteric secretion (3 L). In the small bowel, much
(approximately 90 %) of the water and electrolytes are
reabsorbed with a net amount of 8001,000 mL of fluid
entering the colon. Finally, colonic reabsorption leads to
80100 mL of water excreted with feces daily. It is enough
that the daily fecal water output increases by a minimal
amount (5060 mL) to get loose stools, while a water
excretion of 100 mL results in an increased stool weight
above 200 g/day, which is considered the upper normal
limit (see below) [3]. On the other hand, a decreased water
absorption by only 12 % of the total amount is sufficient
to cause diarrhea in many disorders characterized by an
impaired fluid and electrolyte absorption. Nonetheless, it
should be emphasized that the small bowel and colon
possess a huge fluid and electrolyte reabsorption capacity,
thus providing a powerful salvage mechanism limiting the
occurrence of diarrhea [4].
Various causes (some of them listed in Table 1) may
evoke inflammatory, osmotic, secretory, iatrogenic, and
motility/functional pathophysiological mechanisms under-
lying acute or chronic diarrhea [3]. Notably, causative
factors involved in chronic diarrhea are multifactorial as
they usually activate different pathogenetic mechanisms.
An example in line with this conceptual framework is
represented by cholera, which is the prototype of secretory
diarrhea but may also be associated with altered intestinal
motility leading to rapid bowel transit and reduced intes-
tinal absorption. Likewise, diarrhea related to Clostridium
Table 1 Main features characterizing acute versus chronic diarrhea
Acute Chronic
Duration 14 weeks C4 weeks
Etiology Mainly toxic/infections Heterogeneous
Outcome Usually self-limiting Variable
123
Intern Emerg Med (2012) 7 (Suppl 3):S255S262
difficile toxin A can be the result of a combination of
inflammatory, secretory and motor abnormalities [5, 6].
Acute diarrhea represents the most common subtype of all
diarrheas in terms of frequency, incidence and mortality ([2.5
million deaths/year) and cause of vast direct and indirect costs
to national health care agencies. Acute forms of diarrheal ill-
nesses are usually of short duration (i.e.,\4 weeks) and mainly
related to infectious agents (usually \1 week if viruses or
bacteria are involved; up to 4 weeks if protozoa play a path-
ogenetic role), ingestion of intoxicated foods or food allergy
[7]. Although mainly self-limiting, acute diarrheas may also
represent the start of chronic diarrheal disorders [8]. Chronic
diarrhea can be defined as the production of loose stools (a
conventional quantitative criterion being set at [200 g/day)
for more than 4 weeks. A further definition indicates more than
3 bowel movements/day for more than 3 weeks. According to
published data, its prevalence varies from 1 to 5 % of the
general population [9, 10]. Nonetheless, similar to acute diar-
rhea, also chronic diarrheal disorders may undergo underesti-
mated as patients do not seek for medical care until other
symptoms occur such as weight loss, rectal bleeding, abdom-
inal pain, and urgency of defecation/incontinence. Patients
with chronic diarrhea have a poor quality of life especially if it
is associated to fecal incontinence. As a result, the economic
impact of chronic diarrhea is enormous exceeding several
hundred million dollars/year, which is ascribed to both direct
costs related to diagnostic procedures and hospitalization and
indirect costs related to reduced productivity [11]. The main
characteristics of acute and chronic diarrheas are reported in
Table 2.
Diarrheal disorders often represent a challenge for cli-
nicians, particularly when the symptoms are long-standing.
Indeed, a myriad of possible causative factors should be
carefully considered until a diagnosis is established.
Making an accurate diagnosis is central as the patient may
benefit of an effective management. The next paragraphs
will highlight the principal aspects of the clinical approach
to patients with chronic diarrhea.
Clinical history, physical examination, and principal
laboratory tests
A careful and detailed history taking is a fundamental step
in the diagnostic process of any patients with a chronic
diarrhea [3]. First of all, it is necessary to establish whether
the patient suffers a true diarrheal disorder (i.e., loose
stools, [200 g and increased number of evacuations per
day) or is affected by pseudo-diarrhea (frequent evacua-
tions of small amounts of feces with tenesmus) or just
incontinence that can be caused by an underlying fecaloma
(a rather common complication of chronic constipation in
elderly patients) [12]. A reduced stool consistency or, in
S256
non-absorbable/osmotically active substances introduced
with foods, which accumulate in the intestinal lumen.
Understanding the ending balance of fluids, i.e., the oral
intake in addition to gastrointestinal secretions versus the
amount that is adsorbed, is of crucial importance as it bears
major implications for the complex pathophysiological
mechanisms underlying most forms of diarrhea.
A detailed analysis of physiological mechanisms of
daily fluid fluxes throughout the gastrointestinal tract is
beyond the purpose of the present review. Nonetheless, a
brief account of intestinal fluid absorption/secretion in
physiological condition is relevant to the categorization of
diarrhea and therefore of its clinical approach. Studies have
established that the daily amount of fluid flowing through
the small bowel is about 78 L. This fluid includes oral
intake and saliva (1.5 L), gastric acid secretion and pepsin
(1.5 L), bile and pancreatic secretions (1 L each) and
enteric secretion (3 L). In the small bowel, much
(approximately 90 %) of the water and electrolytes are
reabsorbed with a net amount of 8001,000 mL of fluid
entering the colon. Finally, colonic reabsorption leads to
80100 mL of water excreted with feces daily. It is enough
that the daily fecal water output increases by a minimal
amount (5060 mL) to get loose stools, while a water
excretion of 100 mL results in an increased stool weight
above 200 g/day, which is considered the upper normal
limit (see below) [3]. On the other hand, a decreased water
absorption by only 12 % of the total amount is sufficient
to cause diarrhea in many disorders characterized by an
impaired fluid and electrolyte absorption. Nonetheless, it
should be emphasized that the small bowel and colon
possess a huge fluid and electrolyte reabsorption capacity,
thus providing a powerful salvage mechanism limiting the
occurrence of diarrhea [4].
Various causes (some of them listed in Table 1) may
evoke inflammatory, osmotic, secretory, iatrogenic, and
motility/functional pathophysiological mechanisms under-
lying acute or chronic diarrhea [3]. Notably, causative
factors involved in chronic diarrhea are multifactorial as
they usually activate different pathogenetic mechanisms.
An example in line with this conceptual framework is
represented by cholera, which is the prototype of secretory
diarrhea but may also be associated with altered intestinal
motility leading to rapid bowel transit and reduced intes-
tinal absorption. Likewise, diarrhea related to Clostridium
Table 1 Main features characterizing acute versus chronic diarrhea
Acute Chronic
Duration 14 weeks C4 weeks
Etiology Mainly toxic/infections Heterogeneous
Outcome Usually self-limiting Variable
123
Intern Emerg Med (2012) 7 (Suppl 3):S255S262
difficile toxin A can be the result of a combination of
inflammatory, secretory and motor abnormalities [5, 6].
Acute diarrhea represents the most common subtype of all
diarrheas in terms of frequency, incidence and mortality ([2.5
million deaths/year) and cause of vast direct and indirect costs
to national health care agencies. Acute forms of diarrheal ill-
nesses are usually of short duration (i.e.,\4 weeks) and mainly
related to infectious agents (usually \1 week if viruses or
bacteria are involved; up to 4 weeks if protozoa play a path-
ogenetic role), ingestion of intoxicated foods or food allergy
[7]. Although mainly self-limiting, acute diarrheas may also
represent the start of chronic diarrheal disorders [8]. Chronic
diarrhea can be defined as the production of loose stools (a
conventional quantitative criterion being set at [200 g/day)
for more than 4 weeks. A further definition indicates more than
3 bowel movements/day for more than 3 weeks. According to
published data, its prevalence varies from 1 to 5 % of the
general population [9, 10]. Nonetheless, similar to acute diar-
rhea, also chronic diarrheal disorders may undergo underesti-
mated as patients do not seek for medical care until other
symptoms occur such as weight loss, rectal bleeding, abdom-
inal pain, and urgency of defecation/incontinence. Patients
with chronic diarrhea have a poor quality of life especially if it
is associated to fecal incontinence. As a result, the economic
impact of chronic diarrhea is enormous exceeding several
hundred million dollars/year, which is ascribed to both direct
costs related to diagnostic procedures and hospitalization and
indirect costs related to reduced productivity [11]. The main
characteristics of acute and chronic diarrheas are reported in
Table 2.
Diarrheal disorders often represent a challenge for cli-
nicians, particularly when the symptoms are long-standing.
Indeed, a myriad of possible causative factors should be
carefully considered until a diagnosis is established.
Making an accurate diagnosis is central as the patient may
benefit of an effective management. The next paragraphs
will highlight the principal aspects of the clinical approach
to patients with chronic diarrhea.
Clinical history, physical examination, and principal
laboratory tests
A careful and detailed history taking is a fundamental step
in the diagnostic process of any patients with a chronic
diarrhea [3]. First of all, it is necessary to establish whether
the patient suffers a true diarrheal disorder (i.e., loose
stools, [200 g and increased number of evacuations per
day) or is affected by pseudo-diarrhea (frequent evacua-
tions of small amounts of feces with tenesmus) or just
incontinence that can be caused by an underlying fecaloma
(a rather common complication of chronic constipation in
elderly patients) [12]. A reduced stool consistency or, in
Intern Emerg Med (2012) 7 (Suppl 3):S255S262 S257

Table 2 List of possible etiological factors and related pathogenetic mechanisms responsible for bloody, watery, and fatty diarrhea
Type Pathogenetic mechanisms Causes

Bloody Inflammatory or exudative
(with elevated white blood cell
count, occult or frank blood
or pus in stool)
Watery Secretory (often nocturnal;
unrelated to food intake; fecal
osmotic gap B50 mOsm/kg)
Osmotic (fecal osmotic
gap C125 mOsm/kg)
Functional (distinguished from
secretory types by hypermotility/
rapid gut transit, smaller
volumes and improvement at
night with fasting)
Fatty Malabsorption syndrome
(steatorrhea (damage to or loss
in many of absorptive ability)
but not
all cases)
Maldigestion (loss of digestive
function)
VIPoma vasoactive intestinal polypeptide secreting tumor
Inflammatory diseases: Crohns disease, ulcerative colitis, diverticulitis, ulcerative
jejunoileitis;
Invasive infectious diseases: Clostridium difficile (pseudomembranous colitis), invasive
bacterial infections (e.g., tuberculosis, yersiniosis), invasive parasitic infections (e.g.,
Entamoeba, Giardia, Cryptosporidia, Cyclospora), ulcerating viral infections (e.g.,
cytomegalovirus, herpes simplex virus);
Neoplastic diseaases: Colon carcinoma, lymphoma, villous adenocarcinoma;
Radiation colitis
Alcoholism, bacterial endotoxins (e.g., cholera), bile acid malabsorption, Brainerd
diarrhea (epidemic secretory diarrhea), congenital syndromes, Crohns disease (early
ileocolitis), endocrine disorders (e.g., hyperthyroidism), medications (e.g., antibiotics,
antineoplastics), microscopic colitis (lymphocytic and collagenous subtypes),
neuroendocrine tumors (e.g., gastrinoma, VIPoma, carcinoid tumors), nonosmotic, irritant
laxatives (e.g., senna, cascara), postsurgical (e.g., cholecystectomy, gastrectomy,
vagotomy, intestinal resection), and vasculitis
Carbohydrate (e.g., lactose, fructose) malabsorption syndromes, celiac disease, osmotic
laxatives and antiacids (e.g., magnesium phosphate, sulfate), sugar alcohols (e.g.,
mannitol, sorbitol, xylitol)
Irritable bowel syndrome
Amyloidosis, carbohydrate (e.g., lactose intolerance) malabsorption (late phase), celiac
disease (late phase), gastric bypass, lymphatic damage (e.g., congestive heart failure,
lymphomas), medications (e.g., orlistat, acarbose), mesenteric ischemia, noninvasive
small bowel parasite (e.g., Giardia), post-resection diarrhea, short bowel syndrome, small
bowel bacterial overgrowth (C105 bacteria/mL), tropical sprue, Whipples disease
(Trophoeryma whippelii)
Hepatobiliary disorders, inadequate luminal bile acid, exocrine pancreatic insufficiency

contrast, frequent passage of nut-like stools, abdominal
pain and/or discomfort, is associated with a change in stool
form or frequency, eventually relieved by defecation; the
presence of bloating, sensation of incomplete evacuation or
urge to defecate are all symptoms suggestive of a func-
tional intestinal disorder, such as irritable bowel syndrome
(IBS). Nocturnal diarrhea has long been thought to be
associated with organic diseases (e.g., diabetes and bacte-
rial overgrowth), although recent data challenged this
concept. Furthermore, a thorough review of dietary habits
(e.g., consumption of sugarless candies), drugs used by the
patient (recent antibiotic therapy which may lead to Clos-
tridium difficile related diarrhea or inadvertent/surreptitious
use of laxatives) and recent traveling (increased risk of
bacterial and parasitic infections in developing Countries)
should be considered along with the presence of food
allergy, previous surgeries and any other disorder contrib-
uting to chronic diarrhea [3, 10].
Physical examination provides further support to
establish the underlying cause of a chronic diarrhea. For
example, the presence of edema, overt malnutrition and
signs ascribable to fat soluble vitamin D, K, A and E
deficiency can altogether suggest either malabsorption or
maldigestion diseases. Cramping diarrhea associated with
skin flushing and hepatomegaly can be part of the clinical
spectrum secondary to a metastatic carcinoid. Exoph-
thalmia suggests a diarrhea related to hyperthyroidism,
while an episcleritis may indicate an underlying inflam-
matory bowel disease (IBD). Dermatitis herpetiformis is a
condition associated in about 1525 % of celiac patients
[13].
Finally, rectal examination is important to verify pos-
sible perianal fistulas (Crohns disease), mucosal altera-
tions as well as anal continence, structural abnormalities
(rectocele) and perineal descent which may result in
pudendal neuropathy leading to incontinence.
Fecal examination has diagnostic implications by
revealing: (a) the presence of blood that can be due to a
variety of conditions ranging from hemorrhoids, divertic-
ulosis to IBD and cancer (see below for more details);

123
S258
(b) large volume, pale and oily stools in patients with
classic steatorrhea; (c) floating stools that can be the result
of increased methane or gas content.
Based on the stool characteristics, chronic diarrhea can
be classified into three major types, i.e., bloody (inflam-
matory), watery (secretory/osmotic/functional or increased
gut motility), and fatty (steatorrhea).
Fig. 1 A proposed algorithm for patients presenting with acute diarrhea
Fig. 2 A proposed algorithm for patients with chronic diarrhea
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Intern Emerg Med (2012) 7 (Suppl 3):S255S262
Types of chronic diarrhea
The distinction of diarrhea into the three categories
(bloody, watery, and fatty) may help to focus on the
diagnostic process and possibly limit the number of tests.
Proposed algorithms for acute and chronic diarrhea are
illustrated in Figs. 1 and 2, respectively.
Intern Emerg Med (2012) 7 (Suppl 3):S255S262
Bloody (inflammatory) diarrhea
This form of diarrhea is generally characterized by fre-
quent, small volume, bowel movements. Primary causes of
bleeding include colo-rectal cancer and polyps. Further-
more, the presence of blood (with/without mucus and pus)
in stools is highly indicative of either ulcerative colitis or
Crohns disease [14]. Tenesmus is frequently associated
with inflammatory involvement of the rectum. Physical
examination, revealing abdominal tenderness at palpation,
and cutaneous, ocular and joint involvement, also provides
further evidence for an IBD. Other conditions that should
be taken into account for a differential diagnosis with IBD
are ischemic and radiation colitis. The former is usually
acute, while the latter can be both acute and chronic. A
colonoscopic exam with histopathological analysis of
mucosal biopsies is mandatory for all these diseases.
Infections are rarely responsible for chronic bloody/
inflammatory diarrhea. However, when an infection is
suspected, Campylobacter and Salmonella, particularly in
immunocompromized patients [15], as well as other
bacteria, i.e., Shigella, E. coli 0157:H7, Yersinia, and
Mycobaterium tuberculosis should be sought in stool cul-
tures. Notably, some bacteria require special culture media,
as for E. coli 0157:H7 and Yersinia, otherwise they may
yield false-negative results. Viruses, such as Cytomegalo-
virus and Herpes simplex, along with few parasites, namely
Entameba, Trichuris, and Schistosoma, may also cause
bloody diarrhea. Parasitic infestations may be accompanied
by peripheral blood eosinophilia. If stool cultures are
negative, again colonoscopy (with mucosal biopsy sam-
ples) can be an important diagnostic adjunct. The fecal
recovery of Giardia Lamblia is associated with high false-
negative results and in the suspect of this type of infection a
duodenal aspirate should be obtained during upper gas-
trointestinal endoscopy. Detection of leukocytes in stools is
indicative of infectious/inflammatory processes altering the
gut mucosa [9]. Further exams to be considered in patients
with a suspected inflammatory disease as a cause of bloody
diarrhea include abdominal CT-scan or magnetic resonance
imaging (MRI) often disclosing a bowel wall thickening.
Ultrasonography, more commonly used in Europe rather
than the US, may yield similar results in expert hands.
However, the reliability of bowel wall thickening in the
differential diagnosis of patients with an inflammatory
diarrhea is still unsettled. Finally, although rarely present-
ing with blood in the stools, microscopic colitis (more
broadly being part of collagenous/lymphocytic colitis) can
be the cause of an otherwise undetermined chronic diarrhea
[16]. Colonic biopsies (even in the presence of a normal
mucosa) are fundamental for posing the diagnosis. Eosin-
ophilic gastroenteritis and systemic mastocytosis represent
other rare cause of chronic diarrhea. Since intestinal
S259
anti-inflammatory drugs (e.g., mesalazine, budesonide)
may stop the diarrhea related to microscopic colitis (with
improvement of mucosal histopathology), the evidence
supports this disease as an individual entity [16]. None-
theless, whether bile acid malabsorption or non-steroidal
anti-inflammatory medications may have a role in micro-
scopic colitis still remains an unsolved question.
Watery diarrhea
This type of chronic diarrhea can be due to a heterogeneous
group of conditions characterized by osmotic, functional/
dysmotility, and secretory mechanisms. Osmotic diarrheas
can occur quite commonly in daily practice and are due to
the presence of osmotically active substances which trigger
the passage of water from the plasma to the small bowel
through the highly permeable epithelial lining. This
osmotic mechanism contributes to chronic diarrhea
observed in patients with either malabsorption conditions
such as celiac disease, bacterial overgrowth, use of laxa-
tives (i.e., lactulose, polyethylene glycol and salts), or
maldigestion states, i.e., disaccharidase deficiency and
exocrine pancreatic insufficiency.
With a steadily increasing prevalence (estimated to be
around 1:100 individuals worldwide), celiac disease is one
of the most common conditions causing chronic diarrhea. It
is the result of an immunologic reaction of the mucosa to
gluten and therefore disease-related autoantibodies repre-
sent a good screening test to identify patients with chronic
diarrhea. Specifically, IgA anti-tissue transglutaminase
(tTG) and IgA anti-endomysial antibodies (EMA) are
known to have a very high sensitivity ([95 %) and spec-
ificity (up to 98 %), provided that total IgA levels are
normal (about 3 % of celiac patients may have IgA defi-
ciency) [17, 18]. In this context, anti-deamidated gliadin
antibodies should be tested and they proved to be partic-
ularly useful in young (\2 years) celiac patients. The final
diagnosis must be confirmed by esophago-gastro-duode-
noscopy with duodenal biopsy showing Marsh-Oberhuber
grade 3 villous atrophy in florid cases. About 3040 % of
celiac patients can have increased liver transaminases
which normalize following gluten-free diet [19]. Nonre-
sponsive celiac disease may be associated with complica-
tions (intestinal lymphoma) or associated microscopic
colitis with persistence of a chronic diarrhea [20]. Other
causes of osmotic diarrhea include the use of laxatives such
as magnesium salts (direct osmotic effect), carbohydrate
malabsorption (the classic example being lactulose, an
effective osmotic laxative in patients with chronic consti-
pation) and consumption of poorly absorbable carbohy-
drates (e.g., sugarless candies or chewing gums). All these
possible causes of diarrhea should be excluded by
reviewing carefully the patients medical history. If a
123
S260
disaccharidase (lactase) deficiency is suspected, patients
may undergo H2 breath test to confirm that condition [21,
22]. Notably, the osmotic diarrhea observed in patients
with the aforementioned disorders may result in passage of
nitrogenous substances (azotorrhea) and fat with stools
(steatorrhea) (see below), thus changing its categorization
from watery to fatty diarrhea. Patients with osmotic diar-
rhea respond to fasting with a reduced fecal excretion.
A peculiar dysmotility/functional type of chronic diar-
rhea is detectable in patients with the so-called functional
diarrhea (FD) and diarrhea-predominant IBS (IBS-D)
which affects up to 5 % of the Western population.
Although the etiologic factors underlying both FD and IBS-
D remain unknown, the pathophysiological determinants
are increasingly recognized. Both FD and IBS-D tend to
overlap in the same patients over time and the diagnosis is
now made possible through a positive symptom-based
approach (e.g., Rome criteria) after exclusion of alarm
symptoms/signs [23]. A peculiar form of IBS-D is the
adverse long-term outcome of an acute episode of infec-
tious diarrhea, occurring in about 10 % of all acute, severe
infectious gastroenteritis, the so-called post-infectious IBS.
The infectious agents involved include pathogenic bacteria
(e.g., Salmonella, Shigella, Campylobacter), parasites, and
viruses. Abdominal pain and diarrhea are the most common
symptoms of this syndrome. Risk factors for the develop-
ment of post-infectious IBS include the virulence of the
pathogen, the severity, and duration of the acute enteritis,
younger age, female sex, and psychological disturbances
[24].
Secretory diarrhea is characterized by an active secre-
tion of iso-osmolar fluid by the intestinal epithelium into
the lumen with possible electrolyte abnormalities (e.g.,
hypokalemia and acidosis in patients with VernerMorri-
son syndrome due to a vasoactive intestinal polypeptide
(VIP)-oma, a rare pancreatic neuroendocrine tumor. Diar-
rhea with increased intestinal secretion can be either con-
genital (i.e., congenital chloridorrhea) or acquired, classic
examples being gastroenteropancreatic neuroendocrine
tumors such as gastrinoma (ZollingerEllison syndrome),
ileal carcinoid (carcinoid syndrome), VIPoma (Verner
Morrison syndrome), and glucagonoma. In addition to
classic clinical features (peptic ulcers, esophagitis, secre-
tory diarrhea, flushing, wheezing, and many more), the
measurement of a variety of tumor-related bioactive mes-
sengers (e.g., amines or peptides) can prove the existence
of a neuroendocrine neoplasm. Imaging, including mag-
netic resonance, CT-scan, positron emission tomography,
and endoscopic ultrasound, is needed to localize and stage
the tumor [25]. Some neuroendocrine tumors, e.g., carci-
noids evoking the carcinoid syndrome, may release bio-
active substances, such as serotonin and substance P, which
can also affect gut motility [26].
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Finally, bile acid malabsorption may cause watery
diarrhea usually occurring in patients subjected to ileal
resection (up to 100 cm) due to complicated Crohns dis-
ease. To substantiate the existence of a bile acid malab-
sorption, several tests can be attempted, including assay of
bile salts in the feces ([250 g per day in disease state) [27]
and scintigraphic assessment measuring the degree of
retention and excretion of 75SeHCAT (75-seleniumhomot-
aurocholic acid) at 30 min and 7 days following the
examination (normally the retention is [15 %) [28]. These
examinations, however, cannot be considered for routine
screening. A therapeutic trial with the bile salt sequestering
drug cholestyramine may be advisable and if effective, it
can be used as ex-iuvantibus diagnostic criteria. In contrast
to osmotic, secretory diarrheas are not modified by fasting.
The assessment of osmotic gap in stool water (the for-
mula being 290 - 2[Na?] ? [K?]) may suggest the
underlying pathophysiology of a chronic diarrhea. Specif-
ically, the osmotic gap formula measures the contribution
of electrolytes and non-electrolytes to water retention in the
small bowel lumen. Values of osmotic gap[125 mOsm/kg
are highly suggestive of a pure osmotic diarrhea (with
nonelectrolytes being responsible for most of the fecal
osmolality), while, in contrast, \50 mOsm/kg occur in
pure secretory diarrheas (in that circumstances most of the
fecal osmolality is due to electrolytes); finally mixed
osmotic and secretory diarrheas are characterized by
osmotic gap values ranging from 50 to 125 mOsm/kg [29].
Fatty diarrhea
This type of diarrhea or steatorrhea occurs when the
daily fecal fat output exceeds the normal upper limit, i.e.,
7 g/24 h, which corresponds to 9 % of fats ingested with
meals. However, induced diarrhea in healthy volunteers
evoked a high fecal fat output (up to 13.6 g/24 h) in 35 %
of subjects, thus indicating that steatorrhea can be sec-
ondary to diarrhea per se in the absence of any abnormality
impairing digestion or absorption of dietary fat [30]. As a
result, fecal fat values ranging from 7 to 14 g/24 h have
low specificity for the diagnosis of diseases characterized
by defective digestion or absorption. Only fecal fat output
[14 g/24 h can be predictive of maldigestion or malab-
sorption states.
Fatty diarrhea can be due to two main conditions:
(a) small bowel malabsorption (e.g., celiac disease,
Whipples disease); (b) maldigestion related to exocrine
pancreatic insufficiency. In addition to celiac disease (see
above) and tropical sprue, a rare cause of intestinal mal-
absorption is Whipples disease. This is characterized by
weight loss, diarrhea, arthralgias, pericarditis, and con-
gestive hearth failure. Duodenal biopsy taken during upper
digestive endoscopy is the best way to demonstrate
Intern Emerg Med (2012) 7 (Suppl 3):S255S262
Trophoeryma whippelii (the etiopathogenetic agent) in
Periodic Acid-Schiff-positive macrophages infiltrating the
lamina propria [31]. Steatorrhea may occur as a result of
extensive ileal ([1 m) resection because of a diminished
bile acid reabsorption leading to increased passage of fat
with stools. Mild forms of steatorrhea can be identified in
patients with intestinal infections, including Giardia,
Cryptosporidium, and Cyclospora detectable with appro-
priate microbiological cultures or serological tests.
Pancreatic insufficiency, related to an underlying
chronic pancreatitis or previous pancreatectomy (either
partial or sub-total) may be identified by clinical features
(abdominal pain, weight loss) and the use of fecal elastase
which is not routinely used. Thus, steatorrhea related to
exocrine pancreatic insufficiency can be best proven by an
ex-iuvantibus treatment with pancreatic enzymes.
Therapy
Treatment of chronic diarrhea is aimed at replacing the loss
of fluids and electrolytes and targeting specific diseases
responsible for the intestinal disorder [32]. Oral rehydra-
tion solutions that include glucose or other nutrients and
salt are useful for repletion of body fluids. They can be life-
saving therapy for dehydrating, acute secretory diarrheas,
such as cholera, but have limited application in most
chronic diarrheal states and have not been well studied in
these situations. Although these solutions increase net salt
and water absorption, they are not designed to reduce stool
weight, and diarrhea may even worsen with their use.
Empirical therapy is used either as initial treatment
before diagnostic testing, or after diagnostic testing has
failed to confirm a diagnosis, or even when a diagnosis has
been made, but no specific treatment is available or specific
treatment fails to effect a cure.
Antibiotic therapy could be considered as an initial
therapy if the prevalence of bacterial or protozoal infec-
tion is high in a community or in a specific situation. A
successful trial would eliminate the need for a more
extensive evaluation. Natural and synthetic opiates are
widely used, but other agents, such as bile acid-binding
agents, bismuth, and medicinal fiber, can also be suc-
cessfully prescribed. However, only the most modern
drugs have been studied properly and their use is based on
a considerable body of experience. Most cases of diarrhea,
except for high-volume secretory states, respond to a
sufficiently high dose of opiates. Codeine is less potent
compared to morphine as an anti-diarrheal drug, and the
synthetic opiates, e.g., diphenoxylate and loperamide, are
also less potent but devoid of central effects. The
somatostatin analog octreotide has proven effectiveness in
a variety of neuroendocrine tumors including carcinoid
S261
and other peptide-secreting tumors, as well as dumping
syndrome, and chemotherapy-induced diarrhea. Octreo-
tide does not seem to have any advantage over opiates in
the treatment of chronic idiopathic diarrhea and should be
a second-line agent for this indication because of the need
for administration by injection and costs. Intraluminal
agents include adsorbents, such as clays, activated char-
coal, and binding resins, medicinal fiber but their thera-
peutic efficacy in the treatment of diarrhea has received
negligible and controversial scientific validation. Chole-
styramine and other similar binding resins have reduced
stool weight [33]. Bismuth subsalicylate has been shown
to be effective in acute travelers diarrhea, but its effec-
tiveness in chronic diarrhea is unproven.
Conclusions
A reliable definition of diarrhea is based on three major
features, i.e., increasing water content, volume, and fre-
quency of stool passage. Acute diarrhea is very common
(high prevalence and incidence) in the clinical practice and
is mainly due to infections. Although less frequent than
acute forms, chronic diarrhea represents a clinical chal-
lenge because of the vast array of causes and involved
pathophysiological mechanisms. Thus, an accurate history
taking, physical and rectal examination as well as stool
evaluation are fundamental to establish a diagnosis. Fur-
thermore, categorization of chronic diarrheas based on
stool characteristics (i.e., bloody, watery, and fatty) may
narrow differential diagnosis and guide appropriate tests. A
targeted strategy based on individualized diagnostic work
up is expected to reduce costs for managing patients with
chronic diarrhea.
Conflict of interest None.
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