I. Problem/Condition.

Diarrhea accounts for an estimated 1.8 million physician office visits annually in the United States with an estimated cost of $6 billion per year in healthcare costs and lost productivity. With an estimated 1.8 million hospitalizations per year, diarrhea is one of the most common conditions that hospitalists manage.

Diarrhea is defined as a decrease in stool consistency (soft or liquid) with an increase in stool frequency to three or more bowel movements daily. Severity of the diarrheal illness is defined by the need for change in regular daily activities, where a mild illness requires no change in activities, moderate illness requires some change in activities, and severe illness leads to total disability.

Diarrhea can be further classified by time course (acute vs. chronic), volume (large vs. small), pathophysiology (secretory vs. osmotic) and stool characteristics (watery vs. fatty vs. inflammatory). These classifications are helpful to guide diagnosis and management. Acute diarrhea lasts for less than 14 days, persistent diarrhea lasts for 14-29 days and chronic diarrhea persists for more than 30 days. This chapter will focus specifically on acute diarrhea.

Continue Reading

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

Acute diarrhea is primarily due to infectious causes. Non-infectious etiologies include medication side effects, food allergies, endocrine disorders, underlying gastrointestinal disorder, malignancy.

Infectious diarrhea is most commonly due to viruses but may also be caused by bacteria or parasites. Risk factors for bacterial infections include recent travel, foodborne exposure, or underlying comorbidities (e.g., immunocompromised state). The infectious etiologies, as shown in Table I, are further categorized into noninflammatory or inflammatory causes.

Table I.

Infectious Etiologies of Acute Diarrhea

Non-infectious etiologies include underlying gastrointestinal or endocrine disorders, malignancy, diet, medications and other iatrogenic causes, as shown in Table II.

Table II.

Noninfectious Etiologies of Diarrhea

B. Describe a diagnostic approach/method to the patient with this problem

One of the dilemmas in managing a patient with acute diarrhea is determining when to perform further diagnostic evaluation and when to initiate therapy. Since the majority of acute diarrheal cases are self-limited, diagnostic testing and treatment is usually not necessary. Indications to consider further tests include severe illness (total disability due to diarrhea), bloody stools, fevers, symptoms lasting greater than 7 days.

1. Historical information important in the diagnosis of this problem.

A thorough history can help identify the etiology of acute diarrhea. In particular, details regarding the duration and frequency of symptoms, severity (evidence of dehydration such as increased thirst, decreased urine output, weakness, dizziness, mental status changes) and stool characteristics (presence of blood, mucus, pus, food particles, oil droplets) should be obtained. This information can help identify the origin of the diarrhea to the small bowel (large-volume, non-bloody stools associated with cramping, bloating, gas, and weight loss) or the large bowel (frequent, small-volume stools associated with fever, bloody/mucoid stools and abdominal cramping).

Fever, abdominal pain, and bloody stools suggest an inflammatory infection with invasive bacteria or toxin-producing pathogens. Nausea and vomiting may suggest the presence of pre-formed bacterial toxins and time of onset from ingestion or exposure can provide additional clues for the underlying etiology (e.g., Staphylococcus aureus and Bacillus cereus cause symptoms in less than 6 hours and C. perfringens causes diarrhea 8 to 16 hours after ingestion). Additional historical information include exposures or risk factors, as noted in Table III.

Table III.

Pathogens Causing Diarrhea and Associated Risk Factors

Immunosuppressed patients (e.g., human immunodeficiency virus [HIV], long-term steroid use, chemotherapy, immunosuppressive agents, immunoglobulin deficiency) are at increased risk of all infections, particularly cytomegalovirus, Cryptosporidium, Microsporidium, Isospora and Cyclospora. Transplant patients can develop diarrhea from graft versus host disease. Patients with IgA deficiency can develop severe and refractory giardiasis. Cirrhotic patients are at increased risk of infections with V. parahemolyticus and patients with hemochromatosis can develop Yersinia infections.

Finally, a careful investigation of iatrogenic causes, such as drugs, antibiotics, recent surgery or radiation therapy and possible exposures to pathogens is also warranted. In particular, place of residence, occupational exposures, sexual history, recent travel, pets and hobbies should be thoroughly explored.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

The initial evaluation include evaluation for dehydration (e.g., decreased skin turgor, orthostatic hypotension, tachycardia, dry mucous membranes, delayed capillary refill, sunken eyes). Presence of fever suggests and inflammatory diarrhea. Rectal examination for evaluation of stool may assist in diagnosis. Stool should be examined for consistency and presence of blood. A careful abdominal examination should also be performed to assess for complications (e.g., decreased or absent bowel sounds, abdominal distention, localized or diffuse tenderness, rebound tenderness, and masses).

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Since most cases of acute diarrhea are self-limited, testing should be limited to those patients with moderate-to-severe disease, presence of bloody stools, symptoms lasting greater than 7 days, or immunosuppressed. In patients with evidence of dehydration, bloodwork may include a basic metabolic panel to evaluate for electrolyte disturbances and evidence of renal failure. Stool studies to consider include:

  • Leukocytes, lactoferrin, or calprotectin

  • Microscopy and culture for viruses, bacteria, ova and parasites

  • Clostridium difficile (C. diff) toxin

  • Enzyme-linked immunoabsorbent assay (ELISA) assays for Giardia and Cryptosporidium

  • Abdominal radiograph in toxic patients to look for evidence of ileus or megacolon

The utility of endoscopy is limited but may be considered in cases of severe acute diarrhea with an unclear diagnosis based on above workup and persistent symptoms. Colonoscopy provides direct assessment of the intestinal mucosa which will evaluate for non-infectious causes of acute diarrhea and provide a means for obtaining biopsies of the colon and small intestine.

Esophagogastroduodenoscopy is not currently recommended in patients with acute diarrhea given the low yield since the majority of cases are due to an infectious agent affecting the lower GI tract.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Most cases of acute diarrhea are caused by infections that have a self-limited course and thus usually do not need additional testing to determine the etiology. However, further diagnostic testing is indicated in patients who are immunocompromised or patients who have severe diarrhea with symptoms of toxicity (e.g., fever, bloody stools, peritoneal signs, signs of dehydration) or recent use of antibiotics (associated with C. diff).

First, the patient should be carefully examined for signs of dehydration and systemic toxicity. Fluid repletion is critical early in the presentation even prior to determining the underlying etiology for the patient’s acute diarrheal illness. After initial resuscitation has been completed, a thorough history is obtained to identify the patient’s highest risk of complications, including patients who are immunocompromised (e.g., HIV-positive, transplant recipients, use of immunosuppressive medications, pregnancy or advanced age) and patients with multiple co-morbidities that may decompensate relatively quickly impact (e.g., cirrhosis, renal failure, heart failure).

A complete investigation of the patient’s medications, social history and travel history should be obtained to narrow the differential diagnosis. As discussed above and outlined in Table III, targeted questions can aid in narrowing the differential.

For patients in whom the etiology of acute diarrhea is crucial for management, a diagnostic evaluation is pursued. Infectious causes should be ruled out first as outlined above. If the infectious work-up does not establish a diagnosis, imaging and endoscopy can be used to obtain more data. If the diarrhea persists and continues to worsen, the diagnostic evaluation should be broadened to include chronic causes of diarrhea as the patient’s acute diarrhea may be the first manifestation of a more chronic problem.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

Stool cultures are often obtained unnecessarily with relatively low yield at well under 10% by numerous studies. As a result, the cost of a stool culture per positive result is estimated to be up to $1200. Selective testing is needed to minimize healthcare costs globally. Obtaining a stool culture is recommended only in immunosuppressed patient or in patients with bloody stools, moderate to severe illness, or persistent symptoms for 7 days or longer.

III. Management while the Diagnostic Process is Proceeding

A. Management of acute diarrhea

Most cases of acute diarrhea cases spontaneously resolve, but some patients may need supportive hydration and electrolyte replacement. Oral rehydration solution (ORS), as recommended by the World Health Organization (WHO) and United Nations International Children’s Emergency Fund (UNICEF) has been shown to be a cost-effective method to prevent hospitalizations and manage most cases of infectious diarrhea. The ORS contains water, electrolytes, and maintenance fluid therapy. The composition of oral rehydration solution (per liter of water) include 60-75 milliequivalents/liter (mEq/L) sodium and 75-90 millimoles/liter (mmol/L) glucose. A similar solution can be prepared at home by adding one teaspoon of salt and eight teaspoons of sugar to one liter of water.

Patients with milder severity can often replenish fluid losses with water, soups, fruit juices, and saltine crackers; of note, it is important to provide both glucose and sodium as both these are needed for cotransport in the intestines. Thus, sports drinks (e.g., Gatorade(, Powerade() alone are not sufficient as oral rehydration solutions.

Early initiation of enteral feedings is important in the management of acute diarrheal illness as it will help decrease intestinal permeability seen particular with the invasive pathogens. Although there have been no randomized controlled trials to support a particular diet, the BRAT diet (bananas, rice, apple sauce, toast) or boiled starches and cereals (e.g., potatoes, noodles, rice, wheat and oat) are often recommended. Foods with a high fat content should be avoided until gut function returns to normal. Dairy products should also be avoided since a transient lactase deficiency may occur. Multivitamins and minerals may be supplemented and probiotics may be used as an alternative therapy, especially in cases of traveler’s diarrhea.

Symptomatic treatment is achieved with antisecretory and antimotility agents. The main antisecretory medication available in the United States is bismuth subsalicylate, available over-the-counter in 263 gram tablets. Patients are typically advised to take one or two tablets up to four times daily, with a maximum of eight doses in a 24 hour prior. Side effects including black stools and black tongues as a result of the bismuth sulfide salt in the medication.

The two antimotility drugs that are commonly used are loperamide and diphenoxylate/atropine, the latter of which tends to be more problematic at higher doses due to its central opiate side effects. The antimotility agents are contraindicated in patients with high fever or bloody diarrhea since they may prolong illness or cause worsening severity of illness. Loperamide has been found to decrease the duration of diarrhea by 24 hours in traveler’s diarrhea.

Antibiotic therapy is not required in most cases since the majority of cases are due to viruses or self-limited bacterial infections. In fact, the use of antibiotics is discouraged due to its potential for inducing future resistance, eradicating normal intestinal flora, leading to superinfection i.e. C.Diff infection, prolonging carrier state, or inducing release of toxins. Patients with high likelihood of bacterial infection (i.e. suspected traveler’s diarrhea), severe disease, immunocompromised state, prolonged illness, or public health employment (e.g., food handlers, health care workers) may be considered for empiric antibiotic treatment with one of the following treatment regimens:

  • Levofloxacin 500 milligrams (mg) daily for (x) 1-3 days

  • Ciprofloxacin 750 mg daily x 1 day

  • Ciprofloxacin 500 mg daily x 3 days

  • Ofloxacin 400 mg daily x 1-3 days

  • Azithromycin 1000 mg daily x 1 day

  • Azithromycin 500 mg daily x 3 days

  • Rifaximin 200 mg three times (tid) a day x 3 days

Targeted therapy based on stool culture, if obtained, is available for some of the bacterial and parasitic infections. Treatment regimens may vary based on local resistance and sensitivity panels, but general recommendations include:

  • Campylobacter: azithromycin 500 mg daily x 3-5 days

  • Clostridium difficile: metronidazole 500 mg tid x 10 days, vancomycin (in severe cases)

  • Escherichia coli (except for the Shiga toxin producing strain): ciprofloxacin 500 mg daily x 3 days

  • Shigella: ciprofloxacin 500 mg bid x 3 days or 2 g x 1 day

  • Vibrio cholerae: doxycycline 300 mg x 1 day

  • Giardia: metronidazole 250-750 mg tid for 7 to 10 days

  • Cryptosporidium: nitazoxanide 500 mg bid x 3 days if immunosuppressed

  • Microsporidium: albendazole 400 mg bid x 3 weeks

  • Isospora and cyclospora: Trimethoprim/sulfamethoxazole DS bid x 7-10 days

  • Entamoeba histolytica: metronidazole 750 mg tid and paromomycin 25-35 milligrams/kilogram/day x 5-10 days

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

  • Appropriate oral rehydration solutions must be used. Water alone is inadequate as it does not contain the needed electrolytes, salt, or sugar.

  • Antimotility agents (e.g., loperamide and diphenoxylate/atropine) should be limited to use only in patients with noninflammatory diarrhea. Bismuth subsalicylate is a safer alternative in these patients.

  • Megacolon can develop if antimotility agents are used for prolonged periods.

  • Bismuth subsalicylate can cause salicylate toxicity in patients who are taking aspirin products. It can also cause darkening of the tongue, grayish black stools (which can be confused for melena), and impaction, especially in infants and debilitated patients. Some patients may experience hearing loss and tinnitus.

  • Antibiotics should be avoided in febrile patients with dysentery unless Shiga toxin-producing enterohemorrhagic E.coli is ruled out as antibiotics can precipitate hemolytic- uremic syndrome.

  • Antibiotics should be used judiciously due to the increased risk of C.diff infection and development of resistance.