Transcript Case conference- chronic diarrhea

Case conference
SHANIKA UDUWANA
PGY 1
Case
 Previously healthy, 9-month-old girl presented with a skin
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rash to her pediatrician
was treated with a 10-day course of cefdinir for presumed
impetigo.
She developed diarrhea after 1 day of therapy and had up to
20 loose stools per day. The patient was solely on a cow's
milk-based formula at the time of presentation, which was
then changed to a soy formula.
After antibiotics were discontinued the diarrhea persisted,
prompting a change to a protein hydrolysate formula.
However, the diarrhea continued and the skin rash worsened,
resulting in hospitalization a few weeks later. She had no
history of fever, vomiting, or hematochezia. No other
symptoms were present.
Case cont.
 past medical history was unremarkable.
 She was born at full term with a birth weight of 3.8
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kg. Her growth was normal.
no significant medical issues,
other than cefdinir she was on no medications.
She had no sick contacts or history of travel.
The family history revealed that her mother had
hypothyroidism, but there was no history of any
gastrointestinal illnesses.
The social history was noncontributory.
Case cont.
Examination at the time of hospitalization
 vital signs were normal.
 Her weight and height were at the 50th percentile.
 She was alert, awake, well-developed, mildly dehydrated, and
in no acute distress.
 Skin exam revealed a generalized erythematous rash
consistent with staphylococcal scalded skin syndrome.
 Lung and heart examinations were normal.
 The abdomen was soft, nontender, nondistended, without
hepatosplenomegaly, and with normoactive bowel sounds.
 Rectal exam was normal and negative for occult blood.
 Musculoskeletal and neurologic exams were unremarkable.
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Differentials?
Labs?
Cbc
Bmp
Stool for ova and parasites
Bacterial culture
C difficile toxins A and B
Stool cell count
Reducing substances were measured at 0.75% to 2%
stool pH of 5
glucose breath test were normal
Oral feedings were initially held and diarrhea ceased.
However, upon reintroduction of enteral feeding with
an elemental amino acid-based formula, the diarrhea
resumed.
Osmotic vs secretory?
 when oral intake was discontinued, diarrhea ceased,
indicating that it was an osmotic and not a secretory
type of diarrhea. With the latter, diarrhea continues
upon discontinuation of oral intake.
 Aside from discontinuation of oral intake, another
method for differentiating osmotic from secretory
diarrhea is by evaluation of the stool ion gap,
calculated by the following formula: measured stool
osmolarity - 2 (Na[stool] + K[stool]). Using this formula,
secretory diarrhea presents with normal stool
osmolarity with an ion gap of less than 50 mOsm in
contrast to osmotic diarrhea, which causes increased
osmolarity and a stool ion gap of greater than 100
mOsm
 Osmotic diarrhea is caused by the presence of
unabsorbed nutrients in the GI tract, frequently
secondary to intestinal damage leading to
impairment in digestion or absorption. The most
common form is lactose intolerance in a setting of
infection in which lactose is not being enzymatically
cleaved and absorbed in the small intestine. It then
reaches the colon in an intact form where the colonic
bacteria ferment it causing an osmotic gradient that
drives water into the lumen, leading to diarrhea.
 Secretory diarrhea is characteristically due to
epithelial cells secreting electrolytes and water into
the lumen of the intestine. Several infectious agents,
including Vibrio cholerae, enterotoxigenic
Escherichia coli, and Cryptosporidium parvum, can
cause secretory diarrhea through the production of a
toxin that causes active transport of ions and water
into the lumen. In addition to infectious causes,
some hormones -- such as vasoactive intestinal
peptide, gastrin, serotonin, and acetylcholine -produced by neuroendocrine tumors can cause a
secretory diarrhea.
 What should be the next step in work-up to
determine the etiology of the diarrhea?
 The next step in the evaluation should consider that
this was a case of an osmotic diarrhea, indicating
malabsorption. Therefore, the evaluation should
focus on the nutrient type that is not being efficiently
absorbed, ie, protein, carbohydrate, or fat.
 Positive reducing substances and acidic stool indicate carbohydrate
malabsorption; fecal elastase level and 72-hour fecal fat collection for
calculation of fat clearance can help evaluate for fat malabsorption; and
measurement of the stool alpha-1 antitrypsin level investigates intestinal
protein loss.
 Glucose breath testing was performed to evaluate for the presence of
glucose-galactose transporter defect; findings were negative.
 Further studies that can be performed to determine the specific
carbohydrate that is being malabsorbed include
esophagogastroduodenoscopy (EGD) with histology and additional
duodenal biopsies for determination of disaccharidase levels, and rarely
electron microscopy as well as other carbohydrate-specific hydrogen
breath tests (lactose, sucrose, fructose, and maltose).
 The patient underwent EGD; findings, including histology, were normal.
Dissacharidase levels were consistent with congenital deficiency of
sucrase-isomaltase and maltase. Cow's milk-based formula was restarted
without return of symptoms. The reintroduction of a lactose-containing
formula that does not contain sucrose or isomaltose was sufficient to
resolve the patient's symptoms.
Definition: chronic diarrhea
 Chronic diarrhea is
defined as stool volume
of more than 10
grams/kg/day in infants
and toddlers, or more
than 200 grams/day in
older children for more
than 14 days
FUNCTIONAL DIARRHEA
Defined as the painless passage of three or more large, unformed stools
during waking hours for four or more weeks, with onset in infancy or the
preschool years, and without failure to thrive or a specific definable cause.
This common, benign disorder has also been termed chronic nonspecific
diarrhea of childhood or toddler's diarrhea.
 Children with functional diarrhea usually pass stools only during waking
hours. Early morning stools typically are large and semi-formed, then
stools become progressively looser as the day progresses. Virtually all
children develop normal bowel patterns by four years of age.
 Trials of the following dietary changes are recommended:
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Reduce or eliminate fruit juice or other osmotically active carbohydrates. Apple, prune,
and pear juice contain sorbitol and have a particularly high osmotic load.
Liberalize the fat content of the diet to 35 to 50 percent of total calories.
Other than these two measures, alterations in diet are not helpful and are sometimes
counter-productive.
Postenteritis syndrome
 Most enteric infections in otherwise healthy children resolve
within 14 days and do not develop into a chronic diarrheal illness.
However, in a minority of patients, an acute gastroenteritis can
trigger persistent diarrhea by causing mucosal damage to the
small intestine, termed a "postenteritis syndrome".
 The mechanisms underlying this syndrome are not fully
understood. Contrary to previous hypotheses, sensitization to
food antigens and secondary disaccharidase deficiency, including
lactase deficiency (causing lactose intolerance), are uncommon.
Therefore, international guidelines discourage the use of
hypoallergenic or diluted milk formulas during acute
gastroenteritis. Recurrent or sequential enteric infections may be
responsible for some of these cases.
 In some cases, treatment with probiotic bacteria may facilitate
recovery from postenteritis syndrome.
Bacteria
 In immuno-compromised patients, common infectious causes of
acute diarrhea, such as Campylobacter or Salmonella, can cause
persistent diarrhea. Chronic infections with these pathogens are
uncommon in immuno-competent hosts.
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Bacterial cultures should be part of the initial diagnostic evaluation for all
patients if the stool contains blood, or
for immuno-compromised patients regardless of fecal blood.
 In children recently treated with antibiotics, Clostridium difficile
may cause a colitis characterized by "pseudomembrane" formation.
The enzyme immunoassay available in most laboratories detects C.
difficile toxins A and B with high specificity but only moderate
sensitivity. Polymerase chain reaction (PCR) based diagnostic
methods can enhance the detection rate
Parasites
 Intestinal parasites are an uncommon cause of chronic diarrhea in
developed countries, except among individuals with an
immunodeficiency.
 Specific antigen assays for Giardia and examination from the stool
for parasites is imperative for children with known
immunodeficiencies or with a history of travel to endemic areas.
 These tests are also an appropriate step in the evaluation of
immunocompetent children if initial testing fails to determine a
cause of the chronic diarrhea.
 When a specific parasite is identified, treatment with specific
medications is generally indicated, although the organism may not
always be the cause of the diarrhea. Empiric therapy for enteric
pathogens is generally not advisable.
IMMUNE DEFICIENCY
 Chronic diarrhea may present as a complication of a known
immune deficiency such as HIV disease. Evaluation should focus
on potential infectious causes of the diarrhea, particularly
parasites and opportunistic infections such as Cryptosporidium,
Isospora, and Cyclospora . These children also are at risk for
persistent infectious pathogens that typically cause acute
diarrheas, such as rotavirus
 Chronic diarrhea also may be a presenting symptom of immune
deficiency in a child. When a patient is infected with an unusual
pathogen, or has multiple or recurrent infections of the
gastrointestinal tract or elsewhere, further evaluation for immune
deficiency is required. In rare instances, live vaccines may call
attention to the potential diagnosis of immunodeficiency by
inducing chronic infection. As an example, vaccine-acquired
chronic rotavirus diarrhea has been observed in infants with
severe combined immunodeficiency
ABNORMAL IMMUNE RESPONSE
Celiac disease (also known as gluten-sensitive enteropathy or
nontropical sprue)
 Immune-mediated inflammation of the small intestine caused by
sensitivity to dietary gluten and related proteins in genetically
sensitive individuals.
 Common, occurring in 0.5 to 1 percent of the general population in
most countries.
 Often presents as chronic diarrhea, with or without malnutrition,
during late infancy or early childhood
 Classic clinical features include symptoms of malabsorption such as
diarrhea, steatorrhea, weight loss, or other signs of nutrient or
vitamin deficiency, the presence of characteristic histologic changes
(including villous atrophy) on small intestinal biopsy, and
resolution of the mucosal lesions and symptoms upon withdrawal of
gluten-containing foods, usually within a few weeks to months.
ABNORMAL IMMUNE RESPONSE
Inflammatory bowel disease
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Ulcerative colitis and Crohn's disease are idiopathic chronic inflammatory diseases of the
bowel. These disorders typically present with gradual onset of chronic diarrhea, with or
without blood, from mid-childhood through adulthood
Considered in a child or adolescent presenting with loose stools or bloody diarrhea,
abdominal pain, weight loss or growth failure, perianal disease, anemia, arthritis, or delayed
onset of puberty.
 Extraintestinal manifestations of IBD may involve the skin, joints, liver, eye, bones, and
(rarely) respiratory system
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Laboratory testing often reveals anemia, hypoalbuminemia, and/or an elevated erythrocyte
sedimentation rate; however, laboratory studies are normal in a significant number of
children with IBD
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If the clinical presentation and/or initial laboratory testing support the diagnosis of IBD,
further evaluation should include both small bowel imaging and colonoscopy, (with biopsies
taken from the terminal ileum, if possible). Biopsies from the terminal ileum and each
segment of the colon should be sent for histopathologic examination. Upper endoscopy is
also routinely performed at the time of the initial colonoscopy, and provides further
information as to disease type and extent
ABNORMAL IMMUNE RESPONSE
Allergic enteropathy
 An abnormal immune response to food proteins can cause a proctitis/colitis or an
enteropathy.
 Food protein-induced proctitis/proctocolitis is characterized by blood-tinged stools
in an otherwise healthy infant, and is caused by proteins from cow's milk, or
occasionally soy or other foods, which are ingested through breast milk or standard
cow's milk- or soy-based formulas. Treatment is empiric, consisting of complete
elimination of cow's milk (or other suspected antigen) from the diet. The sensitivity
resolves by one year of age in almost all infants
 Food protein-induced enteropathy is characterized by malabsorption, failure to
thrive, anemia, diarrhea, vomiting, and hypoproteinemia; it is usually induced by
cow's milk protein. The diagnosis is suspected based on clinical features and
confirmed by endoscopy with biopsies, which show villus blunting.
ABNORMAL IMMUNE RESPONSE
Eosinophilic gastroenteritis
 This is an incompletely understood disorder that is sometimes but not
always associated with an identifiable dietary antigen. Approximately onehalf of patients have allergic disease, such as asthma, defined food
sensitivities, eczema, or rhinitis; some patients have elevated serum IgE
levels; rare patients have IgE antibodies directed against specific foods.
Microscopic and collagenous colitis
 Microscopic colitis typically presents with chronic watery nonbloody
diarrhea. typically occurs in middle-aged adults, but occasionally presents
in children. Endoscopy grossly normal, histopathology > abnormal
inflammatory findings, characterized by a collagenous colitis or
lymphocytic colitis, sometimes with an eosinophilic infiltrate. This disorder
may represent an overlap with the eosinophilic gastroenteropathies.
Microscopic colitis in children usually responds well to aminosalicylic acid
(5-ASA) medications. Some cases in adults have been successfully treated
with budesonide.
ABNORMAL IMMUNE RESPONSE
Autoimmune enteropathies
Autoimmune enteropathies are rare disorders that may
present as severe diarrhea during infancy or toddlerhood.
The diarrhea may be isolated, or may occur in association
with diabetes mellitus as part of the IPEX syndrome
(Immune dysregulation, Polyendocrinopathy and
Enteropathy, X-linked), which is associated with mutations
in the FOXP3 gene. IPEX is characterized by chronic
diarrhea, which usually begins in infancy, dermatitis,
autoimmune endocrinopathy (diabetes mellitus,
thyroiditis). Antienterocyte antibodies may be present.
MALDIGESTION OF FAT
Cystic fibrosis
 Cystic fibrosis is the most common cause of pancreatic
exocrine insufficiency in children. The disease may present at
birth with meconium ileus, or may be suggested later by
gastrointestinal symptoms of fat malabsorption, failure to
thrive, rectal prolapse (particularly in the setting of diarrhea)
or pulmonary symptoms.
Other causes of pancreatic insufficiency
 Other causes of pancreatic exocrine insufficiency include
Shwachman-Diamond syndrome (associated with bone
marrow failure and skeletal abnormalities), and two rare
disorders, Pearson syndrome and Johanson-Blizzard
syndrome.
CHOLERHEIC DIARRHEA
 Patients who have undergone resection of the
terminal ileum have impaired absorption of bile
acids. If sufficient bile acids enter the colon, they
may cause a secretory diarrhea.
 Similarly, patients who have had a cholecystectomy
can develop cholerheic diarrhea because the
continuous drainage of bile into the small bowel may
overcome the terminal ileum’s reabsorptive capacity.
BOWEL OBSTRUCTION OR DYSMOTILITY
 Partial bowel obstruction or dysmotility may present
with diarrhea.
 Hirschsprung's disease may present with dysmotility
and diarrhea, and may progress to life-threatening
toxic megacolon
 Intestinal pseudoobstruction
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This disorder of intestinal motility typically presents with
constipation, but patients also may have periods of diarrhea,
particularly if bacterial overgrowth supervenes.
CONGENITAL SECRETORY AND
OSMOTIC DIARRHEAS
 If a congenital diarrhea is suspected, stool electrolytes, pH, fat, and
reducing substances should be measured. A trial of fasting should be
performed to determine if the diarrhea is secretory or osmotic. A marked
decrease in stool output during fasting and high stool osmolarity (eg,
more than 40 mOsm greater than the serum osmolarity) suggests an
osmotic diarrhea
 Mucosal biopsies should be performed in patients with congenital
diarrhea. The findings vary with etiology:
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In congenital chloride diarrhea (CCD) and congenital sodium diarrhea (CSD), the
histology is usually normal.
In enteric anendocrinosis, the mucosal architecture is normal, but special stains
demonstrate absence of enteroendocrine cells.
In tufting enteropathy, the histopathology is characterized by villous atrophy, with
disorganization of the surface enterocytes with focal crowding, resembling tufts.
In microvillus inclusion disease, light microscopy shows a variable degree of hypoplastic
villus atrophy without crypt hyperplasia, and PAS-positive granules at the apical pole of
enterocytes. Electron microscopy reveals characteristic microvillus inclusions and partial
to total atrophy of microvilli on mature enterocytes.
In chylomicron retention disease, light microscopy may reveal lipid droplets in duodenal
enterocytes.
NEUROENDOCRINE TUMORS
 Gastrinoma
In this syndrome, also known as Zollinger-Ellison syndrome, unregulated secretion of
gastrin causes hypersecretion of gastric acid, with consequent peptic ulcer disease and
chronic diarrhea. Fewer than 5 percent of patients present during adolescence. The
disorder may be suspected in a patient presenting with unexplained peptic ulcer disease
and/or with a secretory diarrhea and fat malabsorption. Fasting serum gastrin levels are
elevated 5 to 10 fold.
 VIPoma
Unregulated hypersecretion of vasoactive intestinal polypeptide (VIP) causes watery
diarrhea, hypokalemia, and achlorhydria. VIPomas are very rare in children, but may
occur as ganglioneuromas and ganglioneuroblastomas in the sympathetic ganglia and in
the adrenal glands (rather than in the pancreas where they are often found in adults).
 Mastocytosis
In children, this disorder usually takes the form of cutaneous mastocytosis, consisting
only of the skin lesions of urticaria pigmentosa, and is often self-limited. A few children,
particularly those presenting after 2 years of age, have systemic mastocytosis, which may
include histamine-induced gastric hypersecretion and chronic diarrhea
FACTITIOUS DIARRHEA
 May be characterized by a true increase in stool
volume, which is self-induced (eg, laxative abuse), or
the creation of an apparent increase in stool volume
by the addition of various substances to the stool (eg,
water or urine).
 Diagnosing factitious diarrhea is often difficult and
requires alertness to this possibility, exclusion of
other diseases, and may be aided by specific testing
Questions
1. Which of the following pairs correctly matches an organism with its most likely
source of infection?
A. Adenovirus – unpasteurized milk.
B. Cryptosporidium parvum – contaminated swimming pool.
C. Giardia lamblia – undercooked pork.
D. Plesiomonas – raw pig intestines.
E. Yersinia – contaminated well water.
2. You are evaluating a 7-year-old girl in your office who has a 6-week history of watery,
foul-smelling
diarrhea. She also has experienced some bloating and cramping but no weight loss. She
just returned from summer camp. You suspect giardiasis. Which of the following tests
is the simplest and most reliable in helping you confirm your diagnosis?
A. Duodenal biopsy.
B. Fecal Giardia antigen test.
C. Fecal ova and parasites.
D. Stool culture.
E. String test.
3. Which of the following diarrheal diseases is most likely to present after 6 months of
age?
A. Congenital chloride diarrhea.
B. Congenital sodium diarrhea.
C. Microvillus inclusion disease.
D. Tufted enteropathy.
E. VIPoma.
4. You are evaluating a 6-month-old boy in the hospital. He has had several episodes of
watery diarrhea since the age of 3 months, at which time he was hospitalized for
rotavirus infection. He has been receiving an oral electrolyte solution primarily because
his mother has been reluctant to start him again on his regular milk-based formula. His
weight at 3 months was 5.6 kg; his current weight is 6.2 kg. Except for mild dehydration,
findings on his examination are normal. His electrolyte concentrations are normal,
with the exception of a serum HCO3 of 12 mEq/L (12 mmol/L). Which of the following is
the best next step in
management?
A. Complete bowel rest and initiation of parenteral nutrition.
B. Continuation of his milk-based formula with additional zinc supplementation.
C. Initiation of a full-strength lactose-free, sucrose-free formula.
D. Initiation of an immunologic evaluation.
E. Stool for Giardia fecal antigen and culture.
 Chronic Diarrhea,DOI: 10.1542/pir.26-1-
5,Pediatrics in Review 2005;26;5,James P. Keating
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