Diarrhea
Diarrhea is defined as an increase in the liquidity and/or frequency of the stools
and can be a primary feature of both acute and chronic conditions. It reflects an
increase in stool water content due to impaired water absorption and/or active
water secretion by the intestine. Although the advent of oral rehydration therapy
(ORT) has dramatically reduced the mortality rates in the past 50 years, diarrhea
remains a major cause of morbidity and mortality in children, particularly among
those in developing countries.
PATHOGENESIS AND EPIDEMIOLOGY
Most episodes of diarrhea occur secondary to 1 of 5 types of mechanisms:
malabsorptive, secretory, osmotic, dysmotility, and inflammatory. Malabsorption
is due to a decrease in absorptive surface area, as occurs after intestinal resection
(short bowel syndrome) or with intestinal villous atrophy, as seen in celiac
disease. Secretory diarrhea is caused by secretagogues such as bacterial toxins
(eg, cholera), gut regulatory peptides (eg, vasoactive intestinal polypeptide),
short-chain fatty acids, and bile salts, which can induce intestinal water secretion
while inhibiting absorption. Secretory diarrhea characteristically persists even
when the patient is in a fasting state. Osmotic diarrhea results from the
intraluminal presence of malabsorbed solutes, such as lactose, which exert
significant osmotic pressure that results in secretion of water into the intestines.
In contrast to secretory diarrhea, osmotic diarrhea characteristically decreases or
stops completely during fasting. Dysmotility can lead to increased peristalsis,
causing diarrhea due to rapid transit, or to decreased peristalsis, causing diarrhea
due to bacterial overgrowth. Inflammatory disorders cause diarrhea by several
mechanisms including release of prosecretory eicosanoids and cytokines; altered
tight junction function, decreasing the mucosal absorptive capacity or the
capacity to reabsorb bile acids; and/or disturbances in motility. One or more of
these mechanisms may be operative in an individual during an episode of
diarrhea.
Acute diarrhea (lasting < 1 week in duration) accounts for 2 to 3 million
deaths per year, with most deaths occurring in young children in developing
countries. In the United States, it is estimated that 220,000 children under 5
years of age are hospitalized each year for acute diarrheal illnesses, which
account for 9% of all hospitalizations in this age group. Enteric infections account for most
cases of acute diarrhea, with viruses being responsible for the majority (60–80%)
in children, especially in those under the age of 2 years. Of these, rotaviruses
were previously the most prevalent cause in the United States, but noroviruses
have supplanted rotavirus as the most common cause of medically attended
diarrhea in children in the era of rotaviral vaccination. Worldwide rotavirus
remains the most common cause of moderate to severe diarrhea. This is due to
incomplete penetration of the vaccine and diminished vaccine efficacy in
children in developing countries. In the Northern hemisphere, rotavirus occurs
with a peak incidence in the winter. Other winter-predominant viral agents, such
as astroviruses and caliciviruses, tend to infect older children and cause illness of
shorter duration. Norovirus, a calicivirus, is an important cause of foodborne
illness and causes outbreaks of gastroenteritis in the community, including
schools, daycare centers, hospitals, cruise ships. In contrast to rotavirus,
enteroviruses tend to peak during the summer months and cause diarrhea that is
more prolonged. Viral gastroenteritis is typically transmitted by the fecal-oral
route.
CLINICAL MANIFESTATIONS
Manifestations of acute diarrhea will depend on the causative agent and severity
of involvement. Viral-induced diarrhea typically begins with vomiting followed
by loose to watery stools. The diarrhea may be accompanied by low-grade fever
and abdominal cramping. Most cases are mild and self-limiting with complete
resolution within 5 to 7 days. In moderate to severe cases, excessive fluid and
electrolyte losses can result in dehydration and, in some cases, hypovolemic
shock. Bacterial pathogens often cause diarrhea via toxins that bind to
enterocytes and are eliminated with villous cell turnover. For this reason, the
diarrhea induced by these agents is usually of shorter duration. Common
bacterial pathogens associated with diarrhea include Campylobacter, Shigella,
Salmonella, Yersinia enterocolitica, and various types of Escherichia coli.
Dysentery is characterized by the presence of blood, pus, and mucus in the
stools, and usually occurs with bacterial causes of diarrhea. Shigella is a
common cause of dysentery and is highly contagious, and even a very small
number of organisms can cause infection. In contrast, Salmonella species
generally require high inoculums. Y enterocolitica can cause colitis, appendicitis,
and peritonitis. Enterohemorrhagic E coli, including the prototypical strain
O157:H7, elaborate Shiga-like toxins that predispose to hemolytic uremic
syndrome, typically developing 2 to 14 days after onset of diarrhea.
Enteroinvasive E coli is similar in presentation to Shigella but requires a higher
inoculum. Clostridium difficile causes a disease spectrum ranging from mild
diarrhea to fulminant pseudomembranous colitis. Most cases of C difficile
infection are associated with antibiotic use, but this is not an absolute
requirement for disease. Owing to its formation of persistent spores, C difficile
has become a major source of nosocomial morbidity. Common causes of non–
dysentery bacterial diarrheas include Aeromonas, Plesiomonas, and Vibrio
cholerae. Cholera is the most rapidly fatal diarrheal disease worldwide,
presenting in severe cases with profuse watery (“rice water”) stools leading to
acute dehydration and intravascular volume depletion.
Protozoal enteric infections can manifest either as acute or chronic diarrhea.
Giardia lamblia is a common food and waterborne protozoan that infects the
duodenum. Acute giardiasis is marked by sudden onset of profuse watery
diarrhea, abdominal cramps, bloating, and at times vomiting. Cryptosporidium
parvum typically causes large-volume watery diarrhea, nausea, vomiting, and
fever. It has been associated with communitywide outbreaks and is a relatively
common cause of diarrhea in immunocompromised individuals such as those
with AIDS.
DIAGNOSIS
In children presenting with acute diarrhea, the history should focus on duration
of symptoms, frequency and volume of stool output, and stool characteristics.
Watery diarrhea suggests more proximal small intestinal disease, while diarrhea
containing blood and mucus more commonly implies colonic inflammation.
Vomiting in addition to diarrhea suggests the presence of an organism impacting
the upper intestine, such as enteric viruses, enterotoxin-producing bacteria, or
giardia. Pain in the lower abdomen and rectum or pain with defecation
(tenesmus) indicates distal colonic involvement and inflammation, as seen with
bacterial infections. A history of childcare center attendance, sick contact
exposures, travel to a diarrhea-endemic area, recent use of antimicrobial drugs,
and ingestion of seafood, unwashed vegetables, unpasteurized milk,
contaminated water, or uncooked meats provide valuable clues as to the possible
cause of the diarrhea. Institutionalized children and those recently returning from
developing countries are more likely to have bacterial or parasitic pathogens.
Additional information obtained on history should be aimed at determining
the severity of the stool fluid losses and identifying other conditions that could
place the child at added risk for an adverse outcome. Thirst is an early symptom
of impending dehydration. The amount of oral intake of fluids and voiding
frequency should be determined as part of the history. Increased respiratory rate
or work of breathing may indicate acidosis, while lethargy and a decrease in
sensorium are features of shock. Past histories of underlying chronic disease,
immunodeficiency state, or history of prior intestinal surgery are all important
features to be determined in the history.
In children with acute diarrhea, the physical examination should be focused
on identifying clinical signs of dehydration with careful evaluation of vital signs
and mental status. Loss of skin tissue turgor and a decrease in mucous membrane
moisture are clinical indicators of dehydration. With mild dehydration (0–5%),
the mucus membranes are slightly dry and skin tissue turgor is slightly
decreased. As dehydration progresses to a moderate degree (5–10%), the mucus
membranes will be obviously dry and the decrease in tissue turgor is easily
elicited. Dehydration that progresses beyond this stage (≥ 10%) is accompanied
by additional features of sunken eyes and a sunken fontanelle in the young
infant. Further inadequate replacement of fluid losses will result in hypovolemic
shock, which can lead to death if left untreated. Clinical features of shock
include tachycardia, cool extremities, and delayed capillary refill in the early
stages (state of compensated shock). Children with hypotension and altered level
of consciousness suggest later stages of hemodynamic changes (state of
uncompensated shock).
It is important to differentiate acute infectious diarrhea from acute surgical
conditions and more chronic diarrhea disorders to minimize the potential for
serious morbidity and mortality. Young children with intestinal intussusception
may present with bloody mucoid diarrhea associated with severe cramping,
abdominal pain, inconsolable crying, and, in some cases, lethargy. Acute
appendicitis can present initially with diarrhea prior to onset of the classic
symptoms of abdominal pain. The inflamed appendix can irritate the colon and
produce frequent small-volume mucous-containing stools. This same process
can occur in the case of an intra-abdominal or pelvic abscess. C difficile–induced
pseudomembranous colitis and shigellosis can progress to toxic megacolon, with
potential complications that include perforation, peritonitis, systemic sepsis
syndrome, and shock. Infections with Shiga-like toxin–producing organisms
such as enterohemorrhagic E coli often present with bloody diarrhea and can
progress to the hemolytic uremic syndrome characterized by the triad of
hemolytic anemia, thrombocytopenia, and acute renal insufficiency.
Laboratory tests are seldom required in children with acute diarrhea in the
absence of clinical features of dehydration or other worrisome findings, such as
blood in the stools. The decision to perform any investigations and the choice of
test will depend on the clinical concern. Analysis of a urine sample for specific
gravity, blood, leukocytes, and culture provides information on the child’s
hydration status and may identify a urinary tract infection as the cause of the
diarrhea. Blood samples for determining electrolytes, carbon dioxide, and urea
nitrogen are sometimes needed to evaluate for electrolyte imbalances, acidosis,
and acute renal insufficiency. A complete blood count with differential and
platelet count may help in evaluating for sepsis or the hemolytic uremic
syndrome (anemia and thrombocytopenia). In cases of dysentery or suspected
bacterial causes of diarrhea, stool samples should be sent for microscopy and
culture. Fecal leukocytes indicate the presence of inflammation in response to
invasive or cytotoxin-secreting pathogens but are not a sensitive screening
method. A stool culture should be performed in every child with bloody diarrhea
because bacterial pathogens have been implicated in up to 20% of such cases.
Microbiological investigations should also be considered in the following
circumstances: children with underlying chronic conditions (eg, cancer, sickle
cell disease, inflammatory bowel disease), severe clinical conditions (eg, sepsis),
prolonged symptoms (> 7 days), during outbreaks (eg, childcare, school,
hospital), and a history of travel to at-risk areas. Stool rotavirus assays using
immunologic or polymerase chain reaction (PCR) techniques are widely
available for the diagnosis of this common cause of acute gastroenteritis. Testing
for rotavirus is generally not necessary in cases of suspected viral diarrheas
because it is unlikely to have any impact on the management of the child. More
recently, some centers have begun to use rapid gastrointestinal PCR arrays (eg,
FilmArray) to assess for common viral, bacterial, and protozoal infections.
Diarrhea in the child with a chronic illness, immunocompromised state, or
primary immunodeficiency requires more extensive evaluation for opportunistic
infections. Very young infants are at increased risk for complications of diarrheal
illnesses with dehydration occurring more rapidly in this age group. Infants
under 2 months of age with bacterial diarrhea infections are at increased risk for
an associated bacterial septicemia.
TREATMENT
Treatment of children with acute diarrhea should first be directed toward
preventing dehydration and maintaining nutrition. Maintenance of hydration is
best achieved by replacing stool fluid and electrolyte losses with oral rehydration
solutions at the onset of symptoms. Use of ORT provides rapid, safe, effective,
and inexpensive therapy for diarrheal disease. Oral rehydration solutions are
effective for treating children regardless of the cause of diarrhea or the child’s
serum sodium level at the onset of therapy. Most replacement solutions contain
50 to 90 mmol/L of sodium and 20 to 30 mmol/L of potassium. The addition of
glucose (optimally 110–140 mmol/L or 20–25 g/L) enhances the rate of water
uptake by promoting transport of sodium across the enterocyte via the brush
border membrane glucose-sodium cotransporter. Glucose-sodium–coupled
uptake is an energy-dependent, active process and, as such, occurs rapidly. In
contrast, water uptake is a passive process dependent on the movement of
solutes from the intestinal lumen across the mucosa. Liquids such as fruit juices
and sodas have high levels of sugars but contain insufficient electrolytes to
replace fecal losses and are therefore less effective options. In addition, because
of the high sugar content, they are hypertonic, which can lead to increased stool
water losses. For these reasons, they should not be used in place of appropriate
ORT solutions. In infants, the glucose- and electrolyte-containing ORT solutions
should be offered in addition to the regular breast milk, formula, or solid feeds.
Vomiting is frequently present during the early stages of an acute viral diarrhea
illness but is not a contraindication to the attempted use of oral fluid therapy.
Oral fluids in small volumes at frequent intervals are generally well tolerated and
minimize the potential for vomiting. Children with acute diarrhea who maintain
their hydration status have less anorexia and hence tend to maintain their nutrient
intake. Continued feeding is recommended because amino acids and short-chain
fatty acids promote enterocyte growth and mucosal repair. Although absorption
of nutrients is compromised during an episode of infectious diarrhea, dietary
carbohydrate, protein, and fat can still be absorbed. Children who remain wellnourished
generally recover from the diarrheal illness faster than those in whom
nutritional status is compromised.
For children presenting with clinical signs of dehydration, therapy should be
aimed at first correcting the fluid deficit and then maintaining hydration by
replacing ongoing losses while maintaining nutrition. Correction of fluid deficits
can usually be accomplished via oral administration of appropriate glucose
electrolyte solutions. Intravenous fluid therapy is required in only a small
number of cases in which there is an accompanying ileus or the vomiting is of
such magnitude that oral therapy fails. The fluid deficit is calculated on the basis
of the clinical degree of dehydration and should provide 50 mL/kg body weight
for mild dehydration (5%) and 100 mL/kg body weight for moderate
dehydration (10%). The calculated deficit volume should be replaced over a
period of 4 to 6 hours by offering frequent small volumes from a bottle, cup, or
spoon, or it can be delivered as a continuous slow-rate infusion via a nasogastric
tube. Enteral administration of fluid replacement therapy through a nasogastric
tube is effective and it is associated with fewer side effects than intravenous (IV)
rehydration. However, this practice may be limited by low acceptance by
families and/or healthcare workers. This process can be repeated if the
dehydration is not fully corrected at the end of the 6-hour period. Once the child
is fully rehydrated, the process of providing fluids to maintain hydration should
begin, and the child should be encouraged to resume regular feedings.
Children with moderate to severe dehydration who also have clinical findings
of shock require urgent therapy to reestablish an adequate circulating blood
volume. Fluid resuscitation in these cases requires intravenous administration of
an isotonic crystalline solution such as normal saline. An initial rapid infusion of
20 mL/kg body weight of normal saline will correct the shock in most children
with dehydration due to diarrhea. In those with persistent clinical signs of shock,
a second infusion of 20 mL/kg body weight can be administered. After the
child’s circulatory compromise has been corrected, the process of rehydration
with maintenance therapy and early reintroduction of feeds as outlined
previously should follow.
Antibiotics generally are not recommended for children presenting with acute
bloody diarrhea unless a specific pathogen has been isolated. Antibiotics are
indicated in immunocompromised children or those with septicemia due to
Salmonella, Campylobacter, or Yersinia. In patients with diarrhea due to
enterohemorrhagic E coli, antibiotic therapy has been implicated as a risk factor
for the subsequent development of hemolytic uremic syndrome. Confirmed
shigellosis and cholera should be treated with an antibacterial drug. Depending
on local sensitivities, trimethoprim/sulfamethoxazole or ampicillin may be used
for shigella and azithromycin is most effective in children with cholera. Some
probiotic supplements have been shown to decrease the duration of the acute
diarrheal illnesses. Probiotics may exert an immunomodulatory effect on the host
and static effect on some enteropathogens, thereby altering the intestinal
microflora. Saccharomyces boulardii, a nonpathogenic yeast, has been used to
treat and decrease the recurrence rate of C difficile enterocolitis, and
Lactobacillus rhamnosus GG may lessen the severity of rotaviral dehydration.
Zinc is recommended as an adjunct to ORT in low-income countries. However,
its efficacy in nonmalnourished children is not supported by solid evidence.
Antidiarrheal agents are not recommended in the management of acute
diarrhea in infants and children. Adsorbents such as magnesium aluminum
silicate and psyllium fiber may alter stool consistency but do not reduce absolute
fecal water and electrolyte loss. Smectite has been shown to be effective in
reducing the duration and severity of diarrhea in selected settings including
Europe, South America, Malaysia, and China. Racecadotril, which is not
approved for use in the United States, is effective in reducing the duration and
severity of diarrhea; evidence is stronger in hospitalized children and in selected
settings including Europe, South America, Malaysia, and China. Ondansetron,
administered orally or intravenously, is effective in reducing vomiting and
avoiding hospital admission. A single dose may be considered in young children
presenting to the emergency department with vomiting to ensure oral rehydration
and reduce hospital admissions. However, ondansetron has a warning label from
the US Food and Drug Administration and the European Medicines Agency and
its use therefore is indicated with caution.
Opiate antimotility agents such as loperamide and diphenoxylate-atropine can
cause ileus, nausea, and sedation are generally discouraged. Furthermore, opiateinduced
ileus can cause pooling of secreted fluid in the intestine and may
promote intestinal bacterial overgrowth.
PREVENTION
Enteric pathogens are largely acquired via the fecal oral route and therefore
prevention is accomplished best by public health educational efforts promoting
good hand hygiene, having access to clean water and ensuring safe food
preparation. Use of hand sanitizers containing at least 60% alcohol are beneficial
but are less effective than handwashing with soap and water for infections due to
C difficile. Children with acute diarrhea should be considered contagious until
the diarrhea has completely resolved and should be isolated from groups such as
those attending daycare centers while they are still symptomatic. The rotavirus
vaccine is recommended in all national immunization programs by the World
Health Organization. Its global efficacy has been demonstrated in preventing
against poor outcomes related to acute diarrhea in children younger than 5 years
of age.
Episodes of diarrhea lasting 7 to 13 days are usually defined as prolonged
diarrhea. Duration of 14 days or more is defined as chronic or persistent
diarrhea. Many, but not all, cases of prolonged diarrhea do not resolve and
become chronic or persistent. Most cases of chronic diarrhea occur as a result of
an initial acute infection with an enteric viral or bacterial pathogen. The ensuing
mucosal damage fails to resolve for reasons that are not entirely clear, leading to
a postinfectious enteropathy. Damage to the mucosal brush border can cause
malabsorption due to both loss of intestinal disaccharidases and decrease in the
absorptive surface area. Disaccharidase deficiency results in maldigestion of
carbohydrates with subsequent carbohydrate malabsorption producing an
osmotically induced chronic diarrhea . The prevalence of chronic
diarrhea is geographically dependent and is more common in resource poor
countries. Worldwide estimates vary from 3% to 20% with an incidence of about
3 episodes per child-year. Estimates in the United States are lower at 0.18
episodes per child-year in children ages 6 months to 3 years. The risk for acute
diarrhea becoming chronic depends on many factors, including the initial
pathogenic agent; nutritional status; dietary deficiency of micronutrients such as
zinc, folate, and vitamin A; underlying immunodeficiency; and socioeconomic
conditions. There is some evidence to suggest the incidence of chronic diarrhea
is decreasing worldwide and this may be a result of the introduction of rotavirus
vaccine, which has decreased the incidence of acute diarrhea in young children.
Source : Rudolph’s Pediatrics 23rd ed 2018 Page 5401