Hospital Medicine

Diarrhea; Acute

I. Problem/Condition.

Diarrhea accounts for more than 3.5 million outpatient visits annually. Although most patients can be managed successfully without hospitalization, there are more than 150,000 admissions each year for gastroenteritis, making diarrhea one of the most common conditions that hospitalists manage.

Patients most often describe diarrhea as increased fluidity of the stool; however, it can also be defined as three or more bowel movements daily or a stool weight exceeding 200g in a 24-hour period. Stool weight is less commonly used since fecal weight is largely dependent upon fiber intake.

Diarrhea is considered severe if the stool frequency is more than 5 bowel movements per day, symptoms occur for more than 3 days or if the patient develops systemic symptoms. Diarrhea can be further classified in several ways: 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 for diagnosis and management purposes, especially in patients with persistent symptoms, and should be utilized in combination to improve patient care. This chapter will focus specifically onacute diarrhea.

Acute diarrhea lasts for less than 14 days, persistent diarrhea lasts for 14-29 days and chronic diarrhea persists for more than 30 days. Acute diarrhea is usually self-limited and infectious in etiology. Thus, in the United States, acute diarrheal illnesses are usually seen in the winter months, often due to noroviruses (outbreaks in nursing homes) or rotaviruses and adenoviruses (outbreaks in schools with young children). Non-infectious causes become more common as the diarrhea becomes more chronic.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

Acute diarrhea is primarily due to infectious causes, but can also be a result of non-infectious etiologies such as food poisoning, medications, food allergies and as the initial presentation of chronic diarrhea.

The major infectious causes of acute diarrhea include viral, bacterial or parasitic/protozoal pathogens. Most cases of acute infectious gastroenteritis are likely due to viruses such as norovirus, rotavirus, adenovirus and astrovirus since multiple studies have shown that stool cultures are positive for bacterial or protozoal pathogens in only 1.5 to 5.6% of acute diarrheal cases. Other, more rare causes of viral gastroenteritis, usually found in immunocompromised hosts with chronic diarrhea, include cytomegalovirus and herpes simplex virus, which can cause colonic ulcerations and bloody stools.

Bacterial causes are responsible for most cases of severe diarrhea and are frequently identified in patients who present with bloody diarrhea or food borne outbreaks. Common bacterial causes of acute infectious diarrhea includeCampylobacter,enterotoxigenic Escherichia coliSalmonella, Shigella, Clostridium difficileand thepreformed toxins ofStaphylococcus aureus and Bacillus cereus. Other less common bacterial infections include enterohemorrhagic and enteroinvasiveE. coli, Yersinia, ListeriaVibrioClostridium, Aeromonas and Plesiomonas.

Common protozoal causes of acute infectious diarrhea includeGiardia, Cryptosporidium, Microsporidium, Cyclospora, Isospora and Entamoeba.

Non-infectious causes of acute diarrhea should be considered when diarrhea worsens or becomes chronic despite a negative infectious evaluation. Etiologies include drugs (acarbose, antibiotics, anti-neoplastic agents, colchicine, digoxin, proton pump inhibitors and laxatives), primary gastrointestinal diseases (inflammatory bowel disease and fecal impaction), endocrine disorders (thyrotoxicosis and carcinoid syndrome), iatrogenic causes (Gastrografin used in radiologic studies), malignancy (lymphoma, Kaposi's sarcoma), lactose intolerance and food allergies.

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

One of the dilemmas of manageing a patient with acute diarrhea is determining when to perform further evaluation and initiate therapy. As acute diarrhea is usually self-limited, diagnostic testing is usually not necessary unless the diarrhea becomes severe or persistent, the patient is immunocompromised or if the patient has multiple comorbidities.

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

A thorough medical history can help identify the etiology. In particular, details regarding the duration and frequency of symptoms, severity (evidence of dehydration such as increased thirst, decreased urine output, weakness) 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). This is helpful for the diagnosis of infectious etiologies since they primarily affect either small or large bowel.

Associated symptoms and timing of onset of symptoms can help further narrow the differential. Fever and abdominal pain suggest infections from invasive bacteria or protozoa. Nausea and vomiting are usually associated with pre-formed toxins fromS. aureus andB. cereus. A systemic illness that begins with diarrhea, but progresses to fever, headache, myalgias and neck stiffness may be due toListeria monocytogenes, particularly in pregnant women. The time of onset of symptoms after exposure to the suspected food source can also serve as an important clue (S. aureus andB. cereus cause symptoms in less than 6 hours andC. perfringens causes diarrhea 8 to 16 hours after ingestion). Finally, certain foods are associated with specific intestinal pathogens - unpasteurized dairy products and cold cuts/hot dogs (Listeria), home-canned goods(C. perfringens) pistachios (non-typhoidSalmonella), raspberries (Cyclospora), raw seafood, or coconut milk (Vibrio).

Medical co-morbidities may also change the differential. In addition to the multiple infectious etiologies discussed, immunosuppressed patients are at increased risk of diarrhea from cytomegalovirus, herpes simplex virus,CryptosporidiumMicrosporidium, 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 withV. parahemolyticus and patients with hemochromatosis can developYersinia 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.

There are no specific physical examination maneuvers that can aid the hospitalist in evaluating the underlying cause of diarrhea, but certain findings may be helpful for determining the severity of diarrhea. Signs of dehydration (e.g., decreased skin turgor, orthostatic hypotension, tachycardia, dry mucous membranes and sunken eyes), fever and other signs of systemic toxicity can provide important information about the severity of disease, which should then guide management. A careful abdominal examination should also be performed to assess for complications, with particular attention to the presence or absence of bowel sounds, abdominal distention, localized or diffuse tenderness, presence of rebound, and masses.

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

In patients with co-morbidities that increase the risk of complications or persistent and/or severe symptoms that merits further evaluation to diagnose the cause of the problem, the initial workup for acute diarrhea may include:

  • Complete blood count to look for leukocytosis, neutropenia or anemia

  • Metabolic panel to assess the extent of fluid depletion

  • Stool samples for fecal leukocytes (either stool microscopy, fecal lactoferrin or fecal calprotectin)

  • Stool culture for viruses, bacteria, ova and parasites

  • Stool forClostridium difficile toxin

  • ELISA assays forGiardia andCryptosporidium

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

In cases of severe acute diarrhea where an appropriate management strategy has not yet been identified despite progressive worsening of the patient, endoscopy may be useful. Endoscopy provides direct assessment of the intestinal mucosa with the option of obtaining intestinal biopsies to rule out infections that are difficult to culture (e.g. cytomegalovirus, herpes simplex virus) or inflammatory bowel disease.

Sigmoidoscopy is likely adequate for early investigation, although colonoscopy may be necessary in patients with ileal disease or right-sided colonic disease on imaging. Upper esophagogastroduodenoscopy can also be helpful for diagnosing small bowel disease such as Whipple’s disease, celiac disease (although patients more likely to present with chronic diarrhea), or Crohn’s disease.

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 any further evaluation to determine the etiology. However, if patients are immunocompromised, have severe diarrhea with symptoms of toxicity (e.g. fever, bloody stools, peritoneal signs, signs of dehydration) or have had recent use of antibiotics (associated withC diff), they should have a more comprehensive evaluation.

First, a thorough medical history should be used to identify patients who are at high risk of complications from diarrhea: patients who are immunocompromised (e.g. HIV-positive, transplant recipients, use of immunosuppressive medications, pregnancy or advanced age) and patients with multiple co-morbidities in whom severe diarrhea would have significant 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.

The patient should then be carefully examined for signs of dehydration and systemic toxicity. Complications such as severe abdominal distention, abdominal perforation and abscesses are important for determining the etiology and defining further management.

For patients in whom the etiology of acute diarrhea is crucial for management, a diagnostic evaluation should be 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.

It is unnecessary to initiate a work-up of acute diarrhea within 24 hours of the onset of symptoms, especially if the patient has no associated co-morbidities and is not immunosuppressed. Commonly over-utilized tests include bacterial stool cultures in the absence of any alarm symptoms such as fever, abdominal pain or bloody diarrhea, stool cultures in patients with watery diarrhea and traveler's diarrhea, early use of computed tomography (CT) imaging and sigmoidoscopy/colonoscopy to diagnose colitis.

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 therapy is grossly underutilized in the United States because providers tend to favor intravenous hydration. The composition of oral rehydration solution (per liter of water) recommended by the World Health Organization consists of:

  • 3.5g sodium chloride

  • 2.5g sodium bicarbonate

  • 1.5g potassium chloride

  • 20g glucose or 40g sucrose

A similar solution can be prepared at home by adding one-half teaspoon of salt, one-half teaspoon of baking soda and four tablespoons of sugar to one liter of water. Diluted fruit juices and flavored soft drinks with concomitant saltine crackers/pretzels and seasoned broths may also meet the rehydration needs of patients who are only mildly to moderately ill. It is important to know that the electrolyte concentrations of fluids used for sweat replacement (e.g., Gatorade) are not sufficient as oral rehydration solutions.

Although there have been no randomized controlled trials for diarrheal diets, the BRAT diet (bananas, rice, apple sauce, toast) or boiled starches and cereals (e.g. potatoes, noodles, rice, wheat and oat) may be indicated. 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.

Loperamide and bismuth subsalicylate are the most common anti-diarrheal agents used. Loperamide has been shown to provide faster relief of symptoms than bismuth. Diphenoxylate/atropine is an alternative anti-motility agent, but it has not been studied in randomized controlled trials and may cause cholinergic side effects. The antimotility agents, loperamide and diphenoxylate/atropine, are contraindicated in patients with high fever or bloody diarrhea since they can increase the risk of hemolytic-uremic syndrome. Bismuth subsalicylate may be used for symptomatic therapy in patients with dysentery.

Antibiotic therapy is not required in most cases, but empiric antibiotics should be considered in certain situations such as patients with culture-proven diarrhea, moderate to severe travelers’ diarrhea, more than 8 stools per day, volume depletion, symptoms for more than one week and patients who are being hospitalized or who are immunocompromised. Fluoroquinolones (ciprofloxacin, norfloxacin, levofloxacin) for 3-5 days, azithromycin for 3 days or Bactrim for 3-5 days may be prescribed. Antibiotics should be avoided in patients with suspected or proven enterohemorrhagicE. coli as they can facilitate the development of hemolytic-uremic syndrome.

Other specific antibiotic treatment regimens forC. diff and protozoa are discussed below:

  • C. difficileinfection: Discontinue antibiotics, treat with oral metronidazole or vancomycin (in severe cases) for 10 days

  • Giardia: Metronidazole for 7 to 10 days

  • Cryptosporidium:Nitazoxanide in HIV-negative patients; paromomycin plus azithromycin, in addition to highly active antiretroviral therapy in HIV-positive patients

  • Microsporidium: Albendazole for 3 weeks, in addition to highly active antiretroviral therapy in HIV-positive patients

  • Isospora and cyclospora: Trimethoprim/sulfamethoxazole DS for 7 to 10 days- E. histolytica: 1) metronidazole for 10 days or tinidazole for 3 days for treatment of invasive colitis, followed by 2) either paromomycin for 7 days or iodoquinol for 20 days for cyst clearance

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

  • Loperamide and diphenoxylate/atropine may facilitate the development of the hemolytic-uremic syndrome in patients infected with enterohemorrhagicE. coli

  • Megacolon can develop if antimotility agents are used for prolonged periods. Additionally, they can mask the amount of fluid lost since fluid may pool in the intestine. Thus, fluids should be used aggressively when antimotility agents are used.

  • 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 enterohemorrhagicE.coli is ruled out as antibiotics can precipitate hemolytic- uremic syndrome.

  • Fluoroquinolone resistance (seen inCampylobacter jejuni isolates in South East Asia) has led to increased interest in the use of rifaximin. Rifaximin is also commonly used for traveler’s diarrhea.

  • Empiric antibiotics can increase the risk ofC. diff-associated diarrhea

IV. What's the evidence?

"American Gastroenterological Association medical position statement: Guidelines for the evaluation and management of chronic diarrhea". Gastroenterology. vol. 116. 1999. pp. 1461-63.

Mead, PS, Slutsker, L, Dietz, V. "Foodrelated illness and death in the United States". Emerg Infect Dis. vol. 5. 1999. pp. 607-25.

DuPont, HL. "The growing threat of foodborne bacterial enteropathogens of animal origin". Clin Infect Dis. vol. 45. 2007. pp. 1353-61.

Wiström, J, Jertborn, M, Ekwall, E, Norlin, K, Söderquist, B, Strömberg, A, Lundholm, R, Hogevik, H, Lagergren, L, Englund, G. "Empiric treatment of acute diarrheal disease with norfloxacin. A randomized, placebo-controlled study. Swedish Study Group". Ann Intern Med. vol. 117. 1992.

Manatsathit, S, Dupont, HL, Farthing, M. "Guideline for the management of acute diarrhea in adults". J Gastroenterol Hepatol. vol. 17. 2002. pp. S54-S71.

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