Chronic Diarrhea

Lawrence R. Schiller
Division of Gastroenterology, Baylor University Medical Center, Dallas, TX, USA
Summary
Chronic diarrhea is a common clinical problem, most inclusively
defined as frequent passage of fluid stools lasting more than
1 month. A comprehensive history is the best start to the evaluation.
Probably the most important features to define are the onset
(acute or gradual), pattern (continuous or intermittent), severity
(causing dehydration or not), and type of stool produced (watery,
fatty, or inflammatory). Coexisting symptoms, such as weight loss
or abdominal pain, may be important clues to etiology. Patientswith
irritable bowel syndrome (IBS) should be identified by the presence
of characteristic abdominal pain associated with variable stool form
or frequency, and should be distinguished fromothers with chronic
diarrhea. The differential diagnosis of continuing chronic diarrhea
is broad, but targeted evaluation is often rewarded with a diagnosis
that can be treated.
Case
A 78-year-old woman presents with a 3-year history of diarrhea. The
problem began gradually and is now complicated by episodes of
fecal incontinence. She has watery stools every day, moves her
bowels up to five times a day, and has lost about 2 kg (5 pounds).
She has no abdominal pain, never sees blood in her stools, and has
never been hospitalized for dehydration. Occasional loperamide
reduces stool frequency and urgency of defecation, but does not
eliminate loose stools. She has taken non-steroidal anti-inflammatory
drugs (NSAIDs) for arthritis, but uses no other scheduled
medications. Physical examination is unremarkable, except for
reduced anal sphincter tone and squeeze.
Definition and Epidemiology
Chronic diarrhea is best described as frequent passage of loose
stools formore than 1month [1]. Some patients confuse fecal incontinencewith
diarrhea and a fewconsider frequent passage of formed
stool to be diarrhea, but otherwise patient reports of diarrhea are
usually valid. For clinical purposes, it is best to distinguish chronic
diarrhea fromIBS with diarrhea, in which abdominal pain is prominent
[1, 2]. IBS tends to have more variable stool frequency and
form, typically runs a benign coursewithout medical complications,
and does not need an extensive diagnostic evaluation. In contrast,
patients with chronic diarrhea typically always have loose stools,
may havemedical complications, and often have treatable causes for
chronic diarrhea that can be discovered [3–5]. Therefore, efforts to
make a diagnosis will be rewarded. Surveys suggest that 3–5%of the
population has chronic diarrhea in any given year. It is unclear how
many of these people have IBS as opposed to other causes of chronic
diarrhea.
Pathophysiology
At a fundamental level, diarrhea is caused by excess water in stools
resulting from decreased absorption of fluid from the lumen or
increased secretion of fluid into the lumen [5]. This may occur
because of toxins, hormones, neurotransmitters, bile acids, or
cytokines that affect mucosal absorption directly; because rapid
motility hurries fluid past the absorptive surface; because the
absorptive surface area is reduced or bypassed; or because poorly
absorbed substances are ingested and hold water within the lumen
osmotically.
Clinical Features
Diarrhea is a symptom that most people experience transiently
from time to time, and so there is a universal appreciation of acute
diarrhea. Chronic diarrhea is less common, and patients are often
bewildered when it does not go away spontaneously. Other symptoms
may be present, such as weight loss, evidence of malnutrition,
cramps, bleeding, fecal incontinence, and abdominal pain, which
can produce substantial disability.
While most patients know diarrhea when they have it, few have
a good idea about its severity. Many view the number of stools
per day, coexisting urgency or incontinence, or the intensity of
cramps as key measures. Researchers often consider stool weight
(>200 g/24 hours) to be critical – and in some ways it is – because
stool weights >1000 gmay be associated with dehydration and electrolyte
depletion. However, patients have no idea what their stool
weights are and clinicians typically do not measure stool weight,
depending instead upon weight loss, dehydration, and the intensity
of patient complaints in deciding how severe diarrhea is.
Clinical signs associated with chronic diarrhea are often sparse,
though when present they may be helpful [1,5] (Figure 34.1). Diagnosis and Differential
Diagnosis
Chronic diarrhea can be a symptom of many different conditions
that have multiple diagnostic pathways [5]. Given this complexity,
even experienced clinicians worry about getting the diagnosis right.
Three general approaches can be recommended, depending upon
circumstances [6]:
_ Presumptive diagnosis:When the temporal association of events
and onset, course of illness, and clinical features are characteristic,
making a specific diagnosis likely, and definitive diagnostic tests
are not readily available or are imprecise, and therapy is not risky, a
presumptive diagnosis can bemade and a therapeutic trial should
be instituted.
_ Directed evaluation: When the clinician has a good idea of
the diagnosis or a limited differential diagnosis and a definitive
diagnostic test is available, that diagnostic test should be done to
confirm the diagnosis and to direct further management.
_ Categorization and algorithmic evaluation: When no particular
diagnosis is especially likely, categorizing diarrhea as watery
(with subtypes of secretory and osmotic), inflammatory, or fatty
by simple tests can lead to a series of diagnostic tests that may yield
a diagnosis. A retrospective review from a tertiary referral center
highlights the potential of stool analysis in categorizing the potential
causes of diarrhea [7].
Presumptive diagnosis might be used, for example, in a patient
who developed chronic diarrhea shortly after a cholecystectomy. If
the diarrhea had the expected characteristics of watery stools that
were more numerous in themorning, a therapeutic trial of bile acidbinding
resinwould be warranted, since no definitive diagnostic test

is available and the therapeutic trial would not be risky or expensive.

If the patient improved, the diagnosis of postcholecystectomy diarrhea
would be likely.
Directed evaluation might be employed in a patient who was
likely to have celiac disease based on a characteristic history of
weight loss, bloating, and fatty stools. Serological testing and smallbowel
biopsy have a very high true-positive rate and would confirm
the diagnosis if positive [8]. The thoughtful clinician would obtain
those tests early in the evaluation and proceed on to long-termtreatment
with confidence.
Categorization and algorithmic evaluation make sense when
there is no dominant diagnosis [4]. In this scenario, the extensive
differential diagnosis of chronic diarrhea is limited by categorizing
the type of stool produced as watery, inflammatory, or fatty and
then looking for the specific problems causing that type of diarrhea.
This categorization is done by gross inspection of stools and
by analyzing stools for blood, white blood cells (WBCs) (or a surrogate
marker, such as fecal lactoferrin or calprotectin), and fat (Figure
34.1). Watery stools are easily pourable and have no blood or
pus. Inflammatory stools have blood or pus. Fatty stools have excess
fat or oil.
Watery stools can be subdivided into secretory diarrhea or
osmotic diarrhea based on stool electrolyte analysis [9]. Secretory
diarrhea is caused by incomplete absorption of electrolytes, making
the stools are electrolyte-rich.Osmotic diarrhea is caused by ingestion
of a poorly absorbed substance that obligates water retention
within the lumen tomaintain osmotic equilibration with serum(the
intestine is too permeable to water to allow an osmotic gradient to
develop between the lumen and serum). Electrolyte absorption is
unaffected, so stools have very low electrolyte concentrations. This
distinction can be quantitated by calculating the fecal osmotic gap
(FOG),which estimates the contribution of non-electrolytes to stool
osmolality:
FOG = 290 − 2([Na+] + [K+]),
where 290 is the assumed luminal osmolality and 2([Na +] + [K+])
represents an estimate of the total cations and anions present in stool
water. A FOG >100 mosm/kg suggests osmotic diarrhea, while a
FOG below 25 mosm/kg suggests secretory diarrhea.
Once the diarrhea has been categorized, the differential diagnosis
becomesmoremanageable (Table 34.1) and algorithmic approaches
to each subtype are feasible (Figure 34.2).
Case Continued
Because there is no dominant diagnosis, this patient is most
appropriately evaluated by categorizing the diarrhea and using an
algorithmic approach. Routine laboratory tests, including complete
blood count (CBC), metabolic profile, and C-reactive protein, are
unremarkable. A 48-hour stool collection yields 550 g/24 hours of
watery diarrhea. Fecal occult blood test is negative, fecal lactoferrin is
negative, and stool fat excretion is 2 g/24 hours. Fecal [Na +] is
40 mmol/L and fecal [K+] is 100 mmol/L, making the FOG =
10 mosm/kg, consistent with a secretory diarrhea. Flexible
sigmoidoscopy reveals normal appearances, but biopsies are
interpreted as showing collagenous colitis.
Therapeutics
The treatment of chronic diarrhea ultimately depends on the underlying
condition. For some conditions, therapy can be curative (e.g., a
Table 34.1 Differential diagnosis of chronic diarrhea. Source: Fine 1999. Reproduced
with permission of the American Gastroenterological Association.
Osmotic
diarrhea
Osmotic laxative abuse: Mg++, SO4
−2, PO4
−3, lactulose,
mannitol, sorbitol, PEG
Carbohydrate malabsorption: lactose, fructose, others
Secretory
diarrhea
Congenital chloridorrhea
Chronic infections
IBD: ulcerative colitis, Crohn’s disease (ileum), microscopic
colitis (lymphocytic colitis, collagenous colitis), diverticulitis
Drugs and poisons: stimulant laxative abuse
Disordered regulation: postvagotomy, postsympathectomy,
diabetic neuropathy, IBS
Ileal bile acid malabsorption
Endocrine diarrhea: hyperthyroidism, Addison’s disease
Neuroendocrine tumors: gastrinoma, VIPoma,
somatostatinoma, mastocytosis, carcinoid syndrome,
medullary carcinoma of the thyroid
Other neoplasia: colon carcinoma, lymphoma, villous adenoma
Idiopathic secretory diarrhea: epidemic (Brainerd)
Sporadic
Fatty
diarrhea
Malabsorption syndromes: mucosal diseases, SBS,
postresection diarrhea, small-bowel bacterial overgrowth,
mesenteric ischemia
Maldigestion: pancreatic insufficiency
Reduced luminal bile acid
Inflammatory
diarrhea
IBD: ulcerative colitis, Crohn’s disease, diverticulitis, ulcerative
jejunoileitis
Infections: invasive bacterial infection (Clostridium, E. coli,
tuberculosis, others), ulcerating viral infection (CMV, herpes
simplex), invasive parasites (amebiasis, strongyloides)
Ischemic colitis
Radiation enterocolitis
Neoplasia: carcinoma of colon
Lymphoma
PEG, percutaneous endoscopic gastrostomy; IBD, inflammatory bowel disease; IBS,
irritable bowel syndrome; VIP, vasoactive intestinal polypeptide; SBS, short-bowel
syndrome; CMV, cytomegalovirus.
gluten-free diet for celiac disease) [8]. For relapsing conditions, such
as collagenous colitis, appropriate therapy can induce remission [10].
For all others, symptomatic therapy can diminish the impact of diarrhea
on quality of life, both while evaluation is ongoing and chronically
[11] (Table 34.2).
The most important issue to address is rehydration. Intravenous
fluid is used in hospitalized patients. Oral rehydration can correct
even serious fluid depletion [12]. Intraluminal agents can modify
stool texture, but may not reduce stool output.
Themost effective andmost widely applicable symptomatic therapy
is antidiarrheal opiates [13]. Low-potency opiates include loperamide
and diphenoxylate plus low-dose atropine (to reduce abuse
potential). The key difference in using these agents to treat chronic
rather than acute diarrhea is giving the antidiarrheal on a scheduled
basis (e.g., before eachmeal) instead of on an “as-needed” basis.
Antidiarrheal drugs work best if given before meals, when they can
blunt the physiological stimulus for defecation.
When low-potency opiate antidiarrheal drugs fail to control diarrhea,
higher-potency ones, such as codeine, morphine, or deodorized
tincture of opium, should be used [11]. These agents should
be started at a low dose and titrated up slowly to allow tolerance to
sedative effects to develop in the brain. Tolerance does not develop
to the constipating effects of these agents, so an effective dose
that will control diarrhea but not produce sedation can usually be
achieved.
Clonidine and octreotide have non-specific antidiarrheal activity,
but should be reserved for special cases, such as those that fail opiate
therapy [11].

History
Physical
examination
Routine
laboratory
tests
Stool
analysis
Weight
Watery diarrhea Inflammatory diarrhea Fatty diarrhea
Secretory Osmotic
Electrolytes
Osmotic gap
pH
Carbohydrate
malabsorption
Fecal occult
blood test
Bleeding
Stool WBCs
Inflammation
Fat output
Sudan stain
Quantitative
Laxative screen
Categorize
Onset
Congenital
Abrupt
Gradual
Stool
characteristics
Watery
Bloody
Fatty
Fecal
incontinence
Abdominal pain
Inflammatory
bowel disease
Irritable
bowel syndrome
Ischemia
Weight Ioss
Malabsorption
Neoplasm
Aggravating
factors
Diet
Stress
Mitigating
factors
Diet
OTC drugs
Rx drugs
Previous
evaluation
Iatrogenic
diarrhea
Drugs
Radiation
Surgery
Factitious
diarrhea
Laxatives
Systemic diseases
Hyperthyroidism
Diabetes mellitus
Collagen-vascular
diseases
Tumor syndromes
AIDS
Ig deficiencies
Pattern
Continuous
Intermittent
Duration
Epidemiology
Travel
Food
Water
General
Fluid
balance
Nutrition
Skin
Flushing
Rashes
Dermatographism
Complete blood count
Anemia
Leukocytosis
Chemistry screen
Fluid/electrolyte status
Nutritional status
Serum protein/globulin
Thyroid
Mass
Chest
Wheezing
Heart
Murmur
Abdomen
Hepatomegaly
Mass
Ascites
Tenderness
Anorectal
Sphincter
competence
Fecal occult
blood test
Extremities
Edema
Figure 34.1 Initial diagnostic approach to chronic diarrhea. OTC, over-the-counter; Rx, prescription; AIDS, acquired
immunodeficiency syndrome; Ig,
immunoglobulin; WBC, white blood cell. Source: Fine 1999. Reproduced with permission of the American
Gastroenterological Association.