Diarrhea

Acute diarrhea is defined as the abrupt onset of 3 or more loose stools per day. The augmented water content in the stools (above the normal value of approximately 10 mL/kg/d in the infant and young child, or 200 g/d in the teenager and adult) is due to an imbalance in the physiology of the small and large intestinal processes involved in the absorption of ions, organic substrates, and thus water. A common disorder in its acute form, diarrhea has many causes and may be mild to severe.

Childhood acute diarrhea is usually caused by infection of the small and/or large intestine; however, numerous disorders may result in diarrhea, including a malabsorption syndrome and various enteropathies. Acute-onset diarrhea is usually self-limited; however, an acute infection can have a protracted course. By far, the most common complication of acute diarrhea is dehydration.

Although the term "acute gastroenteritis" is commonly used synonymously with "acute diarrhea," the former term is a misnomer. The term gastroenteritis implies inflammation of both the stomach and the small intestine, whereas, in reality, gastric involvement is rarely if ever seen in acute diarrhea (including diarrhea with an infectious origin); in addition, enteritis is also not consistently present. Examples of infectious acute diarrhea syndromes that do not cause enteritis include Vibrio cholerae–induced diarrhea and Shigella-induced diarrhea. Thus, the term acute diarrhea is preferable to acute gastroenteritis.

Diarrheal episodes are classically distinguished into acute and chronic (or persistent) based on their duration. Acute diarrhea is thus defined as an episode that has an acute onset and lasts no longer than 14 days; chronic or persistent diarrhea is defined as an episode that lasts longer than 14 days. The distinction, supported by the World Health Organization (WHO), has implications not only for classification and epidemiological studies but also from a practical standpoint because protracted diarrhea often has a different set of causes, poses different problems of management, and has a different prognosis.

Diarrhea is the reversal of the normal net absorptive status of water and electrolyte absorption to secretion. Such a derangement can be the result of either an osmotic force that acts in the lumen to drive water into the gut or the result of an active secre­tory state induced in the enterocytes. In the former case, diarrhea is osmolar in nature, as is observed after the ingestion of nonabsorbable sugars such as lactulose or lactose in lactose malabsorbers. Instead, in the typical active secretory state, enhanced anion secretion (mostly by the crypt cell compartment) is best exemplified by enterotoxin-­induced diarrhea.

In osmotic diarrhea, stool output is proportional to the intake of the unabsorbable substrate and is usually not massive; diarrheal stools promptly regress with discontinuation of the offending nutrient, and the stool ion gap is high, exceeding 100 mOsm/kg. In fact, the fecal osmolality in this circumstance is accounted for not only by the electrolytes but also by the unabsorbed nutrient(s) and their degradation products. The ion gap is obtained by subtracting the concentration of the elec­trolytes from total osmolality (assumed to be 290 mOsm/kg), according to the formula: ion gap = 290 – [(Na + K) × 2].

In secretory diarrhea, the epithelial cells’ ion transport processes are turned into a state of active secretion. The most common cause of acute-onset secretory diarrhea is a bacterial infection of the gut. Several mechanisms may be at work. After colonization, enteric pathogens may adhere to or invade the epithelium; they may produce enterotoxins (exotoxins that elicit secretion by increasing an intracellular second messenger) or cytotoxins. They may also trigger release of cytokines attracting inflammatory cells, which, in turn, contribute to the acti­vated secretion by inducing the release of agents such as prostaglandins or platelet-activating factor. Features of secretory diarrhea include a high purg­ing rate, a lack of response to fasting, and a normal stool ion gap (ie, 100 mOsm/kg or less), indicating that nutrient absorption is intact.

Although infectious agents are by far the most common cause for sporadic or endemic episodes of acute diarrhea, one should not dismiss other causes that can lead to the same presentation.

• Causes of diarrhea with acute onset include the following:

  • Infections

    • Enteric infections (including food poisoning)

    • Extraintestinal infections

  • Drug-induced

    • Antibiotic-associated

    • Laxatives

    • Antacids that contain magnesium

    • Opiate withdrawal

    • Other drugs

  • Food allergies or intolerances

    • Cow's milk protein allergy

    • Soy protein allergy

    • Multiple food allergies

    • Olestra

    • Methylxanthines (caffeine, theobromine, theophylline)

  • Disorders of digestive/absorptive processes

    • Glucose-galactose malabsorption

    • Sucrase-isomaltase deficiency

    • Late-onset (adult-type) hypolactasia, resulting in lactose intolerance

  • Chemotherapy or radiation-induced enteritis

  • Surgical conditions

    • Acute appendicitis

    • Intussusception

  • Vitamin deficiencies

    • Niacin deficiency

    • Folate deficiency

  • Vitamin toxicity

    • Vitamin C

    • Niacin, vitamin B3

  • Ingestion of heavy metals or toxins (eg, copper, tin, zinc)

  • Ingestion of plants (eg, hyacinths, daffodils, azalea, mistletoe, Amanita species mushrooms

• Infectious causes of acute diarrhea in developed countries

  • Viruses

    • Rotavirus - 25-40% of cases

    • Norovirus - 10-20% of cases

    • Calicivirus - 1-20% of cases

    • Astrovirus - 4-9% of cases

    • Enteric-type adenovirus - 2-4% of cases

  • Bacteria

    • Campylobacter jejuni - 6-8% of cases

    • Salmonella - 3-7% of cases

    • E Coli - 3-5% of cases

    • Shigella - 0-3% of cases

    • Y enterocolitica - 1-2% of cases

    • C difficile - 0-2% of cases

    • Vibrio parahaemolyticus - 0-1% of cases

    • V cholerae - Unknown

    • Aeromonas hydrophila - 0-2% of cases

  • Parasites

    • Cryptosporidium - 1-3% of cases

    • G lamblia - 1-3% of cases

A study by Yi et al of 207 stool samples from hospitalized children in metropolitan Atlanta, Ga, with health-care–associated vomiting and/or diarrhea found that 20 children (10%) were positive for rotavirus and 7 children (3%) were positive for norovirus. The results indicated that these pathogens have an important role in pediatric nosocomial illness. ^[2]

United States statistics

In the United States, one estimate before the introduction of specific antirotavirus immunization in 2006 assumed a cumulative incidence of 1 hospitalization for diarrhea per 23-27 children by age 5 years, with more than 50,000 hospitalizations. By these estimates, rotavirus was associated with 4-5% of all childhood hospitalizations and a cost of nearly $ 1 billion. ^[3]  Furthermore, acute diarrhea is responsible for 20% of physician referrals in children younger than 2 years and for 10% in children younger than 3 years.

The impact of vaccination on rotavirus morbidity has been remarkable, with significant reduction of diarrhea-associated hospitalizations and visits to emergency departments in children in the years 2007-2008 compared with the prevaccine period. ^[4]

A study by Olortegui et al that included 2082 children reported that 35% of the children experienced astrovirus infections and astrovirus prevalence in diarrheal stools was 5.6%, and severity exceeded all enteropathogens except rotavirus. ^[5]

International statistics

In developing countries, an average of 3 episodes per child per year in children younger than 5 years is reported; however, some areas report 6-8 episodes per year per child. In these settings, malnutrition is an important additional risk factor for diarrhea, and recurrent episodes of diarrhea lead to growth faltering and substantially increased mortality. ^[6]  Childhood mortality associated with diarrhea has constantly but slowly declined during the past 2 decades, mostly because of the widespread use of oral rehydration solutions; however, it appears to have plateaued over the past several years.

Because the single most common cause of infectious diarrhea worldwide is rotavirus, and because a vaccine has been in use for over 3 years now, a reduction in the overall frequency of diarrheal episodes is hoped for in the near future.

A study by Lübbert et al found the incidence of Clostridium difficile infection in Germany in 2012 to be 83 cases per 100,000 population. The chance of recurrence increased with each relapse; an initial recurrence of the infection was found in 18.2% of patients with index events, with 28.4% of these patients having a second recurrence and 30.2% of second-recurrence patients having a third recurrence. ^[7]

Sex- and age-related demographics

Sex

Most cases of infectious diarrhea are not sex specific. Females have a higher incidence of Campylobacter species infections and hemolytic uremic syndrome (HUS).

Age

Viral diarrhea is most common in young children. Rotavirus and adenovirus are particularly prevalent in children younger than 2 years. Astrovirus and norovirus usually infect children younger than 5 years. Yersinia enterocolitica typically infects children younger than 1 year, and the Aeromonas organism is a significant cause of diarrhea in young children.

Very young children are particularly susceptible to secondary dehydration and secondary nutrient malabsorption. Age and nutritional status appear to be the most important host factors in determining the severity and the duration of diarrhea. In fact, the younger the child, the higher is the risk for severe, life-threatening dehydration as a result of the high body-water turnover and limited renal compensatory capacity of very young children. Whether younger age also means a risk of run­ning a prolonged course is an unsettled issue. In developing countries, persis­tent postenteritis diarrhea has a strong inverse correlation with age.

In developed countries, with proper management, prognosis is very good. However, data show an increase in diarrhea-associated deaths among US children from the mid-1980s through 2006. During 2005-2007, 1087 diarrhea-associated infant deaths were reported with 86% of deaths occurring among low birthweight (< 2500g) infants. Risk factors for these infants included male sex, Black race, and low 5-minute Apgar score (< 7). ^[8]

Death is caused predominantly by dehydration and secondary malnutrition from a protracted course. Severe dehydration must be managed with parenteral fluids. Once malnutrition from secondary malabsorption begins, prognosis turns grim unless the patient is hospitalized and supplemental parenteral nutrition is started. Neonates and young infants are at particular risk of dehydration, malnutrition, and malabsorption syndromes.

Even though the mortality rate is low in developed countries, children can die from complications; however, prognosis for children in countries without modern medical care and children with comorbid conditions is more guarded.

Morbidity/mortality

Mortality from acute diarrhea is overall globally declining but remains high. Most estimates have diarrhea as the second cause of childhood mortality, with 18% of the 10.6 million yearly deaths in children younger than age 5 years.

Despite a progressive reduction in global diarrheal disease mortality over the past 2 decades, diarrhea morbidity in published reports from 1990-2000 slightly increased worldwide compared with previous reports. In the United States, an average of 369 diarrhea-associated deaths/year occurred among children aged 1-59 months during 1992-1998 and 2005-2006. ^[9]  The vast majority of diarrhea-associated infant deaths were reported in 2005-2007, with 86% of deaths occurring among low-birthweight (< 2500 g) infants. ^[8]

Furthermore, in countries in which the toll of diarrhea is highest, poverty also adds an enormous additional burden, and long-term consequences of the vicious cycle of enteric infections, diarrhea, and malnutrition are devastating. ^[6]

Complications

Common complications include the following:

• Aeromonas caviae - Intussusception, gram-negative sepsis, hemolytic-uremic syndrome (HUS)

• Campylobacter species - Bacteremia, meningitis, cholecystitis, urinary tract infection, pancreatitis, Reiter syndrome (RS)

• C difficile - Chronic diarrhea

• C perfringens serotype C - Enteritis necroticans

• Enterohemorrhagic E coli - Hemorrhagic colitis

• Enterohemorrhagic E coli O157:H7 - HUS

• Plesiomonas species - Septicemia

• Salmonella species - Seizures, HUS, perforation, RS

• Vibrio species - Rapid dehydration

• Y enterocolitica - Appendicitis, perforation, intussusception, peritonitis, toxic megacolon, cholangitis, bacteremia, RS

• Rotavirus - Isotonic dehydration, carbohydrate intolerance

• Giardia species - Chronic fat malabsorption

• Cryptosporidium species - Chronic diarrhea

• Entamoeba species - Colonic perforation, liver abscess

Enteric fever is caused by S typhi. This syndrome has an insidious onset of malaise, fever, abdominal pain, and bradycardia. Diarrhea and rash (rose spots) appear after 1 week of symptoms. Bacteria may have disseminated at that time, and treatment is required to prevent systemic complications such as hepatitis, myocarditis, cholecystitis, or GI bleeding.

HUS is caused by damage to vascular endothelial cells by verotoxin (released by enterohemorrhagic E coli and by Shigella organisms). Thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure characterize HUS. Symptoms usually develop one week after onset of diarrhea, when the organism may be absent.

RS can complicate acute infections and is characterized by arthritis, urethritis, conjunctivitis, and mucocutaneous lesions. Individuals with RS usually do not demonstrate all features.

Carrier states are observed after some bacterial infections.

• After diarrhea caused by Salmonella organisms, 1-4% of individuals with nontyphoid and enteric fever infections become carriers. The carrier stage for Salmonella organisms is more likely for females, infants, and individuals with biliary tract disease.

• Asymptomatic C difficile carriage may be observed in as many as 20% of hospitalized patients receiving antibiotics and in 50% of infants.

• Rotavirus is excreted asymptomatically in feces of children who were previously infected, typically for as long as 1-2 weeks.

Education is most important for prevention and treatment. Proper ORT prevents dehydration, and early refeeding speeds recovery of intestinal mucosa. With the caregiver, emphasize proper hygiene and food preparation practices to prevent future infections and spread.