Continuing Education Activity

Diarrhea is a common condition that varies in severity and etiology. The evaluation of diarrhea varies depending on duration, severity, and presence of certain concurrent symptoms. Treatment also varies, though rehydration therapy is an important aspect of the management of any patient with diarrhea. This activity reviews the evaluation and treatment of diarrhea and stresses the role of the interprofessional team in caring for patients with this condition.

Objectives:

• Identify the epidemiology of diarrhea.
• Describe the etiologies of acute and chronic diarrhea.
• Outline the management options available for acute and chronic diarrhea.
• Review interprofessional team strategies for improving care coordination and optimizing outcomes for patients with diarrhea.

Introduction

The normal value of water content in stools is approximately 10 mL/kg/day in infants and young children or 200 g/day in teenagers and adults. Diarrhea is the augmentation of water content in stools because of an imbalance in the normal functioning of physiologic processes of the small and large intestine responsible for the absorption of various ions, other substrates, and consequently water.

Acute diarrhea is described as the acute onset of three or more loose or watery stools a day lasting for 14 days or less. However, chronic or persistent diarrhea is labeled when an episode lasts beyond 14 days. Infection commonly causes acute diarrhea. Noninfectious etiologies become more common as the duration of diarrhea becomes chronic. This distinction is important because treatment and management are based on the duration and specific etiology. Rehydration therapy is an important aspect of the management of any patient with diarrhea.[1] Prevention of infectious diarrhea includes proper handwashing to prevent the spread of infection.[2]

The term "acute gastroenteritis" is synonymously used with "acute diarrhea"; however, the former is a misnomer. The term gastroenteritis signifies both gastric and small intestinal involvement, whereas, practically gastric involvement is almost never seen in acute diarrhea even if it is the infective form of diarrhea. Additionally, enteritis is also not always present. Examples of infectious diarrhea without enteritis include cholera and shigellosis. Hence, it is more clinically appropriate to use the term acute diarrhea as opposed to acute gastroenteritis.

Etiology

Diarrhea is categorized into acute or chronic and infectious or non-infectious based on the duration and type of symptoms. Acute diarrhea is defined as an episode lasting less than two weeks. Infection most commonly causes acute diarrhea. Most cases are the result of a viral infection, and the course is self-limited. Chronic diarrhea is defined as a duration lasting longer than two weeks and tends to be non-infectious. Common causes include malabsorption, inflammatory bowel disease, and medication side effects.[3] Following are some important considerations to be made while diagnosing and managing diarrhea as the identification of the etiological agent is very important:

• Stool characteristics vary between different causes, such as consistency, color, volume, and frequency

• Presence or absence of associated intestinal symptoms, such as nausea/vomiting, fever, and abdominal pain

• Exposure to child daycare where commonly encountered pathogens are rotavirus, astrovirus, calicivirus; Shigella, Campylobacter, Giardia, and Cryptosporidium species

• History of the ingestion of infected food, such as raw or contaminated foods

• History of water exposure from swimming pools, camping, or marine environment

• Travel history is crucial as common pathogens affect certain regions; enterotoxigenic Escherichia coli is the predominant pathogen [4]

• Animal exposure has been historically linked with diarrhea, such as young dogs/cats: Campylobacter; turtles: Salmonella [5]

• Predisposing factors such as hospitalization, antibiotic use, immunosuppression[6]

Epidemiology

Norovirus is associated with approximately one-fifth of all infectious diarrhea cases, with similar prevalence in both children and adults, and is estimated to cause over 200,000 deaths annually in developing countries.[7] Historically, rotavirus was the most common cause of severe disease in young children globally. Rotavirus vaccination programs have decreased the prevalence of diarrhea cases associated with rotavirus.

In developing regions, an average of three episodes of diarrhea per child per year is reported in children less than 5 years old. However, certain other areas report six to eight episodes per year per child. In these circumstances, malnutrition plays an additional role in the development of diarrhea.[8]

A common cause of chronic diarrhea includes inflammatory bowel disease, Crohn disease, and ulcerative colitis. In Europe, the incidence of ulcerative colitis and Crohn disease has increased overall from 6.0 per 100,000 person-years in ulcerative colitis and 1.0 per 100,000 person-years in Crohn disease in 1962 to 9.8 per 100,000 person-years and 6.3 per 100,000 person-years in 2010, respectively.[9]

A study conducted by Lübbert et al observed the occurrence of Clostridium difficile related infection in Germany to be 83 cases/100,000 population in 2012. The chance of recurrence escalated with each relapse in these cases.[10]

In the United States, before specific antirotavirus immunization was introduced in 2006 a cumulative occurrence of one hospitalization for the cases of diarrhea per 23-27 children by the age of 5 years was noted. Moreover, over 50,000 hospitalizations were noted. Basing it on these facts, rotavirus was found to be responsible for 4-5% of all childhood hospitalizations costing nearly 1 billion US dollars.[11]

Pathophysiology

Diarrhea is the result of reduced water absorption by the bowel or increased water secretion. A majority of acute diarrheal cases are due to infectious etiology. Chronic diarrhea is commonly categorized into three groups; watery, fatty (malabsorption), or infectious. Another way of classifying the pathophysiology of diarrhea is into secretory and osmotic forms of diarrhea.

Lactose intolerance is a type of watery diarrhea that causes increased water secretion into the intestinal lumen.[12] Patients typically have symptoms of bloating and flatulence along with watery diarrhea. Lactose is broken down in the intestine by the enzyme lactase. The byproducts are readily absorbed by the epithelial cells. When lactase is decreased or absent, lactose cannot be absorbed, and it remains in the gut lumen. Lactose is osmotically-active, and it retains and attracts water leading to watery diarrhea.

Common causes of fatty diarrhea include celiac disease and chronic pancreatitis. The pancreas releases enzymes that are necessary for the breakdown of food. Enzymes are released from the pancreas and aid in the digestion of fats, carbohydrates, and proteins. Once broken down, the products are available for uptake in the gut. Patients with chronic pancreatitis have insufficient enzyme release leading to malabsorption. Symptoms often include upper abdominal pain, flatulence, and foul-smelling, bulky pale stools due to malabsorption of fats.[13]

In the secretory form of diarrhea, bacterial and viral infections are the common causes. In this instance, the watery stool is the result of injury to the gut epithelium. Epithelial cells line the intestinal tract and facilitate the absorption of water, electrolytes, and other solutes. Infectious etiologies cause damage to the epithelial cells which leads to increased intestinal permeability. The damaged epithelial cells are unable to absorb water from the intestinal lumen leading to loose stool.

History and Physical

In developed regions, acute diarrhea is almost always a benign, self-resolving condition, that subsides in a few days. The duration of illness and clinical presentation vary on the basis of the etiology of diarrhea and the host factors. For instance, rotavirus commonly presents with vomiting, dehydration, and more workdays lost than nonrotavirus diarrhea.

Knowledge of certain factors associated with diarrhea, such as volume, consistency, color, and frequency is helpful in distinguishing the source. The following table outlines these characteristics that can be utilized to narrow down the list of differential diagnoses:

Daycare centers are also responsible for certain causes of diarrhea:[14]

• Certain pathogens spread quickly in daycare. These include rotavirus; astrovirus; calicivirus; and Shigella, Giardia, Campylobacter, and Cryptosporidium

• The increasing trend of daycare usage has increased the occurrence of rotavirus and Cryptosporidium-related infections.[15]

As various foods can lead to gastrointestinal infections, food history is important:

• Consumption of raw or contaminated food items is commonly associated with infectious diarrhea.

• Organisms that are commonly found associated with infectious diarrhea include the following:

  • Dairy products - Campylobacter and Salmonella species[16]

  • Eggs - Salmonella species

  • Meats - Clostridium perfringens, Campylobacter, Aeromonas, and Salmonella species

  • Poultry - Campylobacter species

  • Ground beef - Enterohemorrhagic E coli[17]

  • Seafood - Astrovirus, Aeromonas, Plesiomonas, and Vibrio species

  • Pork - C perfringens, Y enterocolitica[18]

  • Oysters - Calicivirus, Plesiomonas, and Vibrio species

  • Vegetables - Aeromonas species and C perfringens

  • The American Academy of Pediatrics advises that when evaluating children with persistent diarrhea, excessive flatulence, bloating, and abdominal pain, the provider should determine the quantity of juice being consumed.[19]

Swimming pools harbor Shigella species and Aeromonas organisms are causative agents of infectious diarrhea in the marine environment. 

Giardia, Cryptosporidium, and Entamoeba stay unaffected by water chlorination; therefore, suspicion for these parasites should be high in contaminated water. Also, there is an association between Campylobacter infection, agriculture, and drinking water.[20]

Travel history is important as it may direct towards the underlying causative agent of infectious diarrhea. Enterotoxigenic E coli is by far the leading cause of traveler's diarrhea. Following are some common associations between certain areas and causative pathogens:

Evaluation

Typically, a patient with acute diarrhea will have a self-limited course and will not require labs or imaging. A stool culture is warranted in a patient with bloody diarrhea or severe illness to rule out bacterial causes. Bloody stools require additional testing for Shiga toxin and lactoferrin. A patient with recent antibiotic use or hospitalization will require testing for Clostridium difficile infection. Imaging is not ordered routinely in a patient with acute diarrhea. However, an abdominal CT may be required when a patient presents with significant peritoneal signs.

A thorough history is important to determine what labs and imaging need to be ordered to distinguish the cause of chronic diarrhea.[21] Basic lab work for a patient with chronic diarrhea includes a complete blood count, basic metabolic panel, stimulating thyroid hormone, erythrocyte sedimentation rate, liver panel, and a stool analysis. The physician should categorize the type of chronic diarrhea as either watery, fatty, or inflammatory based on the patient’s history and physical exam. Once a probable diagnosis is determined, additional labs and testing specific to the suspected etiology should be ordered.

In diarrhea, a stool pH of under 5.5 or the abundance of reducing substances signifies carbohydrate intolerance usually secondary to viral illnesses.[22] It is transient in nature. Enteroinvasive infections affecting the large bowel cause neutrophils and other leucocytes to be shed into the stool. The presence of leukocytes in stools eliminates the possibility of enterotoxigenic E coli, Vibrio, and viruses.

If the stool sample can not be cultured within two hours of specimen collection it should be refrigerated at 4°C or placed in a transport medium. The yield of stool cultures is low; however, it is helpful when the culture is positive. Stool should always be cultured for Salmonella, Shigella, Campylobacter, C Difficile, and Yersinia enterocolitica if there are signs of colitis or if there is fecal leucocytosis.[23]

Looking for Clostridium difficile is advisable in the presence of colitis and/or blood in stools. An important point of note is that acute-onset diarrhea secondary to C difficile infection may also occur with no history of antibiotic use. In diarrheal cases where there is a history of ground beef ingestion and enterohemorrhagic E coli is present in the stool, one should determine the type of E coli. As hemolytic uremic syndrome can be a consequence of infection with E coli O157:H7.[24]

Rotavirus antigen is tested by enzyme immunoassay and latex agglutination of the stool. Enzyme immunoassay can be used to detect adenovirus antigens. Stool examination for ova and parasites is the best way to find parasites. The stool examination should be performed every three days or on alternate days.

Treatment / Management

An important aspect of diarrhea management is replenishing fluid and electrolyte loss. [25] Patients should be encouraged to drink diluted fruit juice, Pedialyte or Gatorade. In more severe cases of diarrhea, IV fluid rehydration may become necessary.[26] Eating foods that are lower in fiber may aid in making stool firmer. A bland 'BRAT' diet including bananas, toast, oatmeal, white rice, applesauce and soup/broth is well tolerated and may improve symptoms. [27] Anti-diarrheal therapy with anti-secretory or anti-motility agents may be started to reduce the frequency of stools. However, they should be avoided in adults with bloody diarrhea or high fever because they can worsen severe intestinal infections. Empiric antibiotic therapy with an oral fluoroquinolone can be considered in patients with more severe symptoms. Probiotic supplementation has been shown to reduce the severity and duration of symptoms and should be encouraged in patients with acute diarrhea.

The treatment of chronic diarrhea is specific to the etiology. [28] The first step is to categorize diarrhea into watery, fatty or inflammatory. Once categorized, an algorithm can be used to determine the next step in management. Most cases require additional fecal studies, lab work or imaging. More invasive procedures like colonoscopy or upper endoscopy may be required.

In 2003 the recommendations were put forward by the Center for Disease Control (CDC) for the treatment of acute diarrhea in children on both the outpatient and inpatient basis including indications for referral.[29]

Indications for referral and further medical evaluation of children include the following:

• Under 3 months old

• Weighs less than 8 kg (17.6 lbs)

• History of premature birth, chronic illnesses, or concurrent medical conditions

• Fever of 38ºC (100.4 F) or higher in children less than 3 months old or 39ºC (102.2 F) or higher in children between 3 and 36 months of age

• Grossly bloody stool

• High-output diarrhea

• Persistent vomiting

• Signs of dehydration, such as sunken eyes, decreased tear film, dry mucous membranes, and oliguria/anuria

• Mental status alterations

• Inadequate response to oral rehydration or the caregiver is unable to administer oral rehydration

Treatment of dehydration is summarized in the following table:

Therapies advised for some nonviral causes of diarrhea include the following:

• E coli - Trimethoprim-sulfamethoxazole (TMP-SMX). Parenteral second- or third-generation cephalosporins are indicated for systemic complications.

• Aeromonas species - Third-generation and fourth-generation cephalosporins (cefixime).

• Campylobacter species - Erythromycin

• C difficile - Discontinue causative antibiotics. Use oral metronidazole or vancomycin. Vancomycin is reserved for the child who is seriously ill.

• C perfringens - Antibiotics are not recommended for treatment.

• Cryptosporidium parvum - paromomycin and nitazoxanide.

• Entamoeba histolytica - Metronidazole followed by paromomycin or iodoquinol.

• G lamblia - Metronidazole or nitazoxanide.

• Plesiomonas species - TMP-SMX or any other cephalosporin.

• Salmonella species - Treatment prolongs carrier state. TMP-SMX is the first-line medication but there is resistance. Use ceftriaxone and cefotaxime for invasive disease.

• Shigella species - Treatment shortens illness duration. TMP-SMX is the first-line medication but there is resistance. For invasive disease, cefixime, ceftriaxone, and cefotaxime are recommended.

• V cholerae - Doxycycline is the first-line and erythromycin is the second-line antibiotic.

• Yersinia species: TMP-SMX, cefixime, cefotaxime, and ceftriaxone are used.

Differential Diagnosis

Following are the differentials that need to be considered when dealing with a patient with diarrhea:

• Appendicitis

• Carcinoid tumor

• Giardiasis

• Glucose-galactose malabsorption

• Intestinal enterokinase deficiency

• Intussusception

• Meckel diverticulum imaging

• Pediatric Crohn disease

• Pediatric hyperthyroidism

• Pediatric malabsorption syndromes

Prognosis

In developed regions, with proper management, the prognosis is very good. However, data reveal an increase in diarrhea-related mortality among US children between the mid-1980s and 2006. Between 2005 and 2007, 1087 diarrhea-related infant deaths were recorded with 86% of deaths occurring in low birthweight (less than 2500 g) infants. Risk factors for these included male gender, black ethnicity, and low Apgar score (less than 7).[30]

Dehydration and secondary malnutrition become the common causes of death. Parenteral fluids should be given for severe dehydration. Once malnutrition ensues, the prognosis becomes grave unless parenteral nutrition is started in a hospital setting.

Complications

Common complications of common pathogens are:

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

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

• C difficile - Chronic diarrhea

• C perfringens - Enteritis necroticans

• Plesiomonas species - Septicemia

• Enterohemorrhagic E coli O157:H7 - HUS

• Enterohemorrhagic E coli - Hemorrhagic colitis

• Salmonella species - Seizures, RS, HUS, perforation, enteric fever

• Vibrio species - Rapid dehydration

• Giardia species - Chronic fat malabsorption

• Rotavirus - Isotonic dehydration, carbohydrate intolerance

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

• Cryptosporidium species - Chronic diarrhea

• Entamoeba species - Liver abscess, colonic perforation

Deterrence and Patient Education

Education is crucial for prevention and treatment. Proper oral rehydration therapy prevents dehydration. Intestinal mucosa heals faster if refeeding is started earlier. With caregivers, emphasize hygiene and proper food preparation practices in order to prevent infections in the future and their spread. 

Proper handwashing can prevent the spread of infectious diarrhea. Patients with infectious diarrhea should not return to work, school, or daycare until their symptoms have resolved. Professionals should encourage parents to vaccinate their children against rotavirus, a common etiology of viral diarrhea. Probiotic therapy can be considered in patients taking antibiotics to prevent C. difficile colitis.[31]

To decrease the chance of traveler’s diarrhea, encourage patients to drink bottled water, avoid raw fruits and vegetables, and only eat hot, well-cooked foods when they are traveling to developing countries. Bottled water should be used even when brushing teeth. Prophylactic antibiotics for traveler’s diarrhea are usually not recommended. Antibiotics can be considered in individuals with underlying medical diseases who may be affected more significantly by diarrhea.[32]

Enhancing Healthcare Team Outcomes

There are many causes of diarrhea and the condition is best managed by an interprofessional team that includes nurses and pharmacists. Most cases of diarrhea can be prevented by maintaining good personal hygiene and handwashing. In addition, the key is to hydrate the patients. Most viral cases do not require specific treatment but bacterial causes may require antibiotics.

The outcomes for patients who are well hydrated are excellent but patients at extremes of age may not tolerate any degree of dehydration.[33][34]