Jonathan A. Maisel
DIARRHEA
EPIDEMIOLOGY
Diarrhea is defined as three or more watery stools per day.
PATHOPHYSIOLOGY
There are four basic mechanisms:
Increased intestinal secretion (eg, cholera)
Decreased intestinal absorption (eg, enterotoxins, inflammation, or ischemia)
Increased osmotic load (eg, laxatives, lactose intolerance)
Abnormal intestinal motility (eg, irritable bowel syndrome, neuropathy)
Approximately 85% of cases are infectious in etiology.
CLINICAL FEATURES
Determine if the diarrhea is acute (<3-week duration) or chronic (>3 weeks). Acute diarrhea is more likely to represent a serious problem, such as infection, ischemia, intoxication, or inflammation.
Inquire about associated symptoms. Features such as fever, pain, presence of blood, or type of food ingested may help in the diagnosis of infectious gastroenteritis, food poisoning, diverticulitis, or inflammatory bowel disease.
Neurological symptoms can be seen in certain diarrheal illnesses, such as seizure with shigellosis or hyponatremia, or paresthesias and reverse temperature sensation with ciguatoxin.
Details about the host can also better define the diagnosis. Malabsorption from pancreatic insufficiency or HIV-related bowel disorders need not be considered in a healthy host.
Dietary practices, including frequent restaurant meals, exposure to day care centers, consumption of street-vendor food or raw seafood, overseas travel, and camping with the ingestion of lake or stream water, may isolate the vector and narrow the differential diagnosis for infectious diarrhea (eg, lakes or streams—Giardia, oysters—Vibrio; rice—Bacillus cereus; eggs—Salmonella; and meat—Campylobacter, Staphylococcus, Yersinia, Escherichia coli, or Clostridium).
Certain medications, particularly antibiotics, col-chicine, lithium, and laxatives, can all contribute to diarrhea.
Travel may predispose the patient to enterotoxigenic E. coli or Giardia.
Social history, such as sexual preference, drug use, and occupation, may suggest diagnoses such as HIV-related illness or organophosphate poisoning.
The physical examination begins with assessment of hydration status.
Abdominal examination can narrow the differential diagnosis as well as reveal the need for surgical intervention. Even appendicitis can present with diarrhea in up to 20% of cases.
Rectal examination can rule out impaction or presence of blood, the latter suggesting inflammation, infection, or mesenteric ischemia.
DIAGNOSIS AND DIFFERENTIAL
The most specific tests in diarrheal illness all involve examination of the stool in the laboratory.
Stool culture testing should be limited to severely dehydrated or toxic patients, those with blood or pus in their stool, immunocompromised patients, and those with diarrhea lasting longer than 3 days. Consider testing for Salmonella, Shigella, Campylobacter, Shiga toxin-producing E. coli, or amoebic infection. Make the laboratory aware of which pathogens you suspect.
In patients with diarrhea >7 days, those who have traveled abroad, or consumed untreated water, an examination for ova and parasites may be useful to rule out Giardia or Cryptosporidium. Multiple samples may be required.
Assay for Clostridium difficile toxin may be useful in ill patients with antibiotic-associated diarrhea or recent hospitalization.
Because most diarrheal illnesses are viral or self-limited, laboratory testing in routine cases is not indicated. However, in extremely dehydrated or toxic patients, electrolyte determinations and renal function tests may be useful. (Hemolytic-uremic syndrome, characterized by acute renal failure, thrombocytope-nia, and hemolytic anemia, may complicate E. coli 0157:H7 infections in children and the elderly.)
If toxicity is suspected, tests for levels for theophyl-line, lithium, or heavy metals will aid in the diagnosis.
Radiographs are reserved for ruling out intestinal obstruction or pneumonia, particularly Legionella.
CT scanning or angiography may be indicated to diagnose acute mesenteric ischemia.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
The treatment of diarrhea consists of correcting fluid and electrolyte problems.
Initiate specific therapy for any life-threatening cause identified in the initial workup.
Replacement of fluids can be intravenous (boluses of 500 mL IV in adults, 20 mL/kg in children) with normal saline solution in seriously ill patients.
Mildly dehydrated patients who are not vomiting may tolerate an oral rehydrating solution-containing sodium (eg, Pedialyte) as well as glucose to enhance fluid absorption (glucose transport unaffected by enterotoxins). The World Health Organization advocates a mixture of 4 oz orange juice, 8 tsp sugar, and 1 tsp salt in 1 L boiled water. The goal is 50 to 100 mL/kg over the first 4 hours.
As patients tolerate, introduce a “BRAT” diet (bananas, rice, apples, toast).
Patients should avoid raw fruit, caffeine, and lactose and sorbitol-containing products.
Antibiotics are recommended for adult patients with severe or prolonged diarrhea. (See section on acute infectious and traveler’s diarrhea.) Antibiotics should be avoided in infectious diarrhea due to E. coliO157:H7.
Antidiarrheal agents, especially in combination with antibiotics, have been shown to shorten the course of diarrhea. (See section on acute infectious and traveler’s diarrhea.)
Antibiotic-associated diarrhea often responds to withdrawal of the offending drug. Metronidazole or vancomycin may be indicated in selected situations (see section on Clostridium difficile infection).
Almost all true diarrheal emergencies (eg, GI bleed, adrenal insufficiency, thyroid storm, toxicologic exposures, acute radiation syndrome, and mesenteric ischemia) are of noninfectious origin. Patients with these conditions require intensive treatment and hospitalization.
Toxic or severely dehydrated patients, particularly infants and the elderly, warrant admission.
Patients with an unclear diagnosis, but favorable examination findings after hydration, can be discharged home safely.
ACUTE INFECTIOUS AND TRAVELER’S DIARRHEA
EPIDEMIOLOGY
Norovirus causes 50% to 80% of all infectious diarrheas in the United States, followed much less frequently by non-Shiga toxin-producing E. coli, C. difficile, invasive bacteria (Campylobacter, Shigella, Salmonella), Shiga toxin-producing E. coli, and protozoa.
A history of foreign travel, with consumption of contaminated food or drink, is associated with an 80% probability of bacterial diarrhea, primarily toxin and non-toxin-producing strains of E. coli.
PATHOPHYSIOLOGY
Intestinal absorption occurs through the villi, and secretion occurs through the crypts. Fluids are absorbed passively with the transport of sodium, and actively with the absorption of glucose.
Selected enterotoxins disrupt the structure of intestinal villi preferentially, with less involvement of the crypts. As a result, diarrhea occurs because of diminished intestinal villi absorption and unopposed crypt secretion. The glucose dependent mechanism of water reabsorption is unaffected by these toxins, allowing for therapeutic oral rehydration.
DIAGNOSIS AND DIFFERENTIAL
Patients with severe abdominal pain, fever, and bloody stool should undergo stool studies for specific pathogens, including culture for Salmonella, Shigella, Campy lobacter, and E.coli O157:H7; assay for Shiga toxin; and microscopy or antigen assay for Entamoeba histolytica.
Exposure of a traveler or hiker to untreated water, and illness that persists for more than 7 days, should prompt an evaluation for a protozoal pathogen. Stool should be tested by enzyme immunoassay for E. histolytica antigen, Giardia intestinalis antigen, and Cryptosporidium parvum antigen.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Treatment of moderately severe infectious diarrhea (including viral causes) includes antibiotics, antimo-tility agents, fluid resuscitation (oral or parenteral), and dietary modification (BRAT diet—bananas, rice, apples, toast).
Ciprofloxacin 500 milligrams as a single dose, or 500 milligrams twice daily for 3 days will shorten the duration of illness by approximately 24 hours. (Similar dosing for culture proven Shigella or enterotoxigenic, enteropathogenic, or enteroin-vasive E. coli. However, both antibiotics and anti-motility agents should be avoided in cases of Shiga toxin-producing E. coli O157:H7).
Trimethoprim/sulfamethoxazole, TMP 10 milligrams/kg/day :SMX 50 milligrams/kg/day (maximum dose TMP 160 milligrams:SMX 800 milligrams) for 3 days is indicated for children or nursing mothers.
Metronidazole 750 milligrams PO three times per day for 5 to 10 days is indicated for Giardia or Entamoeba infection. Add iodoquinol 650 milligrams three times per day for 20 days, or paromomycin 500 milligrams three times per day for 5 to 10 days, for the latter.
Antimotility agents, such as loperamide 4 milligrams initially, then 2 milligrams following each unformed stool (16 milligrams/d maximum), will shorten the duration of symptoms when combined with an antibiotic. Alternative agents include bismuth subsali-cylate 30 mL or 2 tablets every 30 minutes for 8 doses, or diphenoxylate and atropine 4 milligrams four times per day.
Avoid antimotility agents in the subset of patients with bloody or suspected inflammatory diarrhea because of the potential for prolonged fever, toxic megacolon in C. difficile patients, and hemolytic uremic syndrome in children infected with Shiga-toxin producing E. coli.
Most patients can be discharged home. Educate patients regarding the need for frequent hand washing to minimize transmission.
Provide work excuses to patients employed in the food, day care, and health care industries.
Any toxic-appearing patient should be admitted. Consider admission for those at extremes of age as well.
Individuals should be counseled about the proper selection of food and beverages consumed when traveling abroad, as well as the use of water for drinking, brushing teeth, and the preparation of food and infant formula.
CLOSTRIDIUM DIFFICILE-ASSOCIATED INFECTION, DIARRHEA, AND COLITIS
EPIDEMIOLOGY
Broad-spectrum antibiotics—most notably clindamycin, cephalosporins, ampicillin, amoxicillin, and fluoroqui-nolones—alter gut flora in such a way that C. difficile can flourish within the colon, causing enteropathy.
Transmission of the organism can occur from contact with humans and fomites.
Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients, and is now reported to affect healthy adults who were not exposed to a hospital setting.
PATHOPHYSIOLOGY
Clostridium difficile is an anaerobic bacillus which secretes two toxins that interact in a complex manner to cause illness ranging from secretory diarrhea to pseudomembranous colitis.
Recent antibiotic use, GI surgery or manipulation, severe underlying illness, chemotherapy, and advanced age are risk factors for developing pseudomembranous colitis.
Pseudomembranous colitis is an inflammatory bowel disorder in which membrane-like yellowish plaques of exudate overlay and replace necrotic intestinal mucosa.
CLINICAL FEATURES
Onset is typically 7 to 10 days after initiating antibiotic treatment, but may occur up to several weeks following treatment.
Clinical manifestations can vary from frequent, watery, mucoid stools to a toxic picture, including profuse diarrhea, crampy abdominal pain, fever, leu-kocytosis, and dehydration.
DIAGNOSIS AND DIFFERENTIAL
The diagnosis is confirmed by the demonstration of C. difficile toxin in stool. Colonoscopy is not routinely needed to confirm the diagnosis.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Mild C. difficile infection in an otherwise healthy patient can be treated with discontinuing the offending antibiotic, confirmation of infection, and clinical monitoring.
Metronidazole 500 milligrams PO every 6 hours for 10 to 14 days is the treatment of choice in patients with mild to moderate disease who do not respond to conservative measures.
Patients with severe diarrhea, those with a systemic response (eg, fever, leukocytosis, or severe abdominal pain), and those whose symptoms persist despite appropriate outpatient management, must be hospitalized and should receive vancomycin 125 to 250 milligrams PO four times daily for 10 to 14 days. The symptoms usually resolve within a few days.
Patients with pseudomembranous colitis complicated by toxic megacolon or intestinal perforation require immediate surgical consultation. Rarely, emergency colectomy may be required for fulminant colitis.
Use of antidiarrheal agents is controversial. Relapses occur in 10% to 25% of patients.
CROHN’S DISEASE
EPIDEMIOLOGY
Crohn’s disease is a chronic, idiopathic, granulo-matous inflammatory disease, characterized by segmental ulceration of the gastrointestinal (GI) tract anywhere from the mouth to the anus.
PATHOPHYSIOLOGY
Pathologically, one sees intermittent, longitudinal, deep ulcerations penetrating all layers of the bowel wall, resulting in fissures, fistulas, and abscesses.
CLINICAL FEATURES
The clinical course is variable and unpredictable, with multiple remissions and exacerbations.
Patients commonly report a history of recurring fever, abdominal pain, and diarrhea over several years before a definitive diagnosis is made. Abdominal pain, anorexia, diarrhea, and weight loss occur in most cases.
Patients may also present with complications of the disease, such as intestinal obstruction, intra-abdominal abscess, or a variety of extra-intestinal manifestations.
One-third of patients develop perianal fissures, fistulas, abscesses, or rectal prolapse. Fistulas occur between the ileum and sigmoid colon, the cecum, another ileal segment, or the skin, or between the colon and the vagina. Abscesses can be intraperito-neal, retroperitoneal, interloop, or intramesenteric.
Obstruction, hemorrhage, and toxic megacolon also occur. Toxic megacolon can be associated with massive GI bleeding.
Up to 50% of patients develop extraintestinal manifestations, including arthritis, uveitis, nephrolithiasis, and skin disease (eg, erythema nodosum, pyoderma gangrenosum). Hepatobiliary disease, including gallstones, pericholangitis, and chronic active hepatitis is commonly seen, as is pancreatitis.
Some patients develop thromboembolic disease as a result of a hypercoaguable state.
Malabsorption, malnutrition, and chronic anemia develop in long-standing disease, and the incidence of GI tract carcinoma is triple that of the general population.
The recurrence rate for those with Crohn’s disease is 25% to 50% when treated medically; higher for patients treated surgically.
DIAGNOSIS AND DIFFERENTIAL
The definitive diagnosis of Crohn’s disease is usually established months or years after the onset of symptoms. A careful and detailed history for previous bowel symptoms that preceded the acute presentation may provide clues to the correct diagnosis.
Abdominal CT scanning is the most useful diagnostic test, potentially revealing bowel wall thickening, mesenteric edema, abscess formation, and fistulas, as well as extra-intestinal complications (eg, gallstones, renal stones, sacroiliitis).
Colonoscopy can detect early mucosal lesions, define the extent of colonic involvement, and identify colon cancer.
The differential diagnosis of Crohn’s disease includes lymphoma, ileocecal amebiasis, sarcoidosis, chronic mycotic infections, tuberculosis, Kaposi’s sarcoma, Campylobacter enteritis, and Yersiniaileocolitis. Most of these conditions are uncommon, and the latter two can be differentiated by stool cultures.
When confined to the colon, ischemic colitis, infectious colitis, pseudomembranous enterocolitis, irritable bowel syndrome, and ulcerative colitis should be considered.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Initial evaluation should determine the severity of the attack and identify significant complications.
Laboratory evaluation should include complete blood count, chemistries, and type and cross match when indicated.
Plain abdominal x-rays may identify obstruction, perforation, and toxic megacolon, which may appear as a long, continuous segment of air-filled colon greater than 6 cm in diameter.
CT of the abdomen is the most useful test to confirm the diagnosis, and identify both intra and extra-intestinal manifestations.
Initial ED management includes intravenous fluid replacement, parenteral analgesia, bowel rest, correction of electrolyte abnormalities, and nasogastric suction if obstruction, ileus, or toxic megacolon is present.
Additional treatment may include:
Sulfasalazine 3 to 5 grams/d is effective for mild to moderate Crohn’s disease, but has multiple toxic side effects, including GI and hypersensitivity reactions. Mesalamine, up to 4 grams/d, is equally effective, with fewer side effects.
Glucocorticoids (prednisone) 40 to 60 milligrams/d provides symptom relief, but does not alter the course of the disease.
Immunosuppressive drugs, 6-mercaptopurine 1 to 1.5 milligrams/kg/d or azathioprine 2 to 2.5 milligrams/kg/d, are used as steroid-sparing agents, in healing fistulas, and in patients with serious surgical contraindications.
Antibiotics canhelp induce remission. Ciprofloxacin 500 milligrams every 8 to 12 hours, metronidazole 500 milligrams every 6 hours, and rifaximin 800 milligrams twice daily, are effective.
Patients with medically resistant, moderate to severe Crohn’s disease may benefit from the anti-tumor necrosis factor antibody infliximab 5 milligrams/kg IV.
Diarrhea can be controlled by loperamide 4 to 16 milligrams/d, diphenoxylate 5 to 20 milligrams/d, or cholestyramine 4 grams 1 to 6 times daily.
Hospital admission is recommended for those who demonstrate signs of fulminant colitis, peritonitis, obstruction, significant hemorrhage, severe dehydration, or electrolyte imbalance, or those with less severe disease who fail outpatient management.
Surgical intervention is indicated in patients with intestinal obstruction or hemorrhage, perforation, abscess or fistula formation, toxic megacolon, or perianal disease, and in some patients who fail medical therapy.
Alterations in therapy should be discussed with a gas-troenterologist, and close follow-up must be ensured for patients discharged from the ED.
ULCERATIVE COLITIS
EPIDEMIOLOGY
Ulcerative colitis is an idiopathic chronic inflammatory and ulcerative disease of the colon and rectum, characterized clinically by intermittent episodes of crampy abdominal pain and bloody diarrhea, with complete remission between bouts.
PATHOPHYSIOLOGY
The illness is characterized by mucosal inflammation, with the formation of crypt abscesses, epithelial necrosis, and mucosal ulceration. The deeper layers of bowel are typically spared. The disease increases in severity more distally, with rectal involvement in nearly every case.
CLINICAL FEATURES
Patients with mild disease (>50%), typically limited to the rectum, have fewer than four bowel movements per day, no systemic symptoms, and few extraintestinal manifestations.
Patients with moderate disease (25%) have colitis extending to the splenic flexure.
Severe disease (pancolitis) is associated with frequent daily bowel movements, weight loss, fever, tachycardia, anemia, and more frequent extraintestinal manifestations, including peripheral arthritis, ankylosing spondylitis, episcleritis, uveitis, pyoderma gangreno-sum, erythema nodosum, hepatobiliary disease, thromboembolic disease, renal stones, and malnutrition.
Complications include GI hemorrhage (most common), abscess and fistula formation, obstruction secondary to stricture formation, and acute perforation.
There is a 10- to 30-fold increase in the risk of developing colon carcinoma.
The most feared complication is toxic megacolon, which presents with fever, tachycardia, dehydration, and a tender, distended abdomen. Radiograph reveals a long, continuous segment of air-filled colon > 6 cm in diameter. Perforation and peritonitis are life-threatening complications.
DIAGNOSIS AND DIFFERENTIAL
The diagnosis of ulcerative colitis may be considered with a history of abdominal cramps, diarrhea, and mucoid stools.
Laboratory findings are nonspecific, and may include leukocytosis, anemia, thrombocytosis, decreased serum albumin levels, abnormal liver function test results, and negative stool studies for ova, parasites, and enteric pathogens.
Abdominal CT scanning is important for the diagnosis of nonspecific abdominal pain or for suspected colitis.
Colonoscopy can confirm the diagnosis and define the extent of colonic involvement.
The differential diagnosis includes infectious, ischemic, radiation, anti-neoplastic agent induced, pseudomembranous, and Crohn’s colitis.
When the disease is limited to the rectum, consider sexually acquired diseases, such as rectal syphilis, gonococcal proctitis, lymphogranuloma venereum, and inflammation caused by herpes simplex virus, Entamoeba histolytica, Shigella, and Campylobacter.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Patients with severe disease should be admitted for intravenous fluid replacement, parenteral analgesia, bowel rest, correction of electrolyte abnormalities, and nasogastric suction if obstruction, ileus, or toxic megacolon are present.
Consultation with both gastroenterology and surgery should be arranged for patients with significant GI hemorrhage, toxic megacolon, and bowel perforation.
The following interventions should be considered:
Intravenous antibiotics, such as ciprofloxacin 400 milligrams every 8 to 12 h, and metronidazole 500 milligrams every 6 h.
Parenteral steroid treatment with either hydro-cortisone 100 milligrams every 8 h, methylpred-nisolone 16 milligrams every 8 h, or prednisolone 30 milligrams every 12 h.
The majority of patients with mild and moderate disease can be treated as outpatients.
Therapy listed below should be discussed with a gas-troenterologist, and close follow up must be ensured.
For mild active proctitis and left sided colitis, mesalamine suppositories or enemas are effective. However, topical steroid preparations (beclometha-sone, hydrocortisone) may be better tolerated.
For patients who do not respond to or tolerate topical therapy, oral mesalamine is an effective alternative.
If topical therapy or oral mesalamine is unsuccessful, prednisone 40 to 60 milligrams/d can induce a remission. Once clinical remission is achieved, steroids should be slowly tapered and discontinued.
In refractory cases, 3. combination of glucocorticoids and immunomodulators, such as 6-mercaptopu-rine 1 to 1.5 milligrams/kg per day or azathioprine 2 milligrams/kg per day should be considered.
Supportive measures include a nutritious diet, physical and psychological rest, replenishment of iron stores, dietary elimination of lactose, and addition of bulking agents, such as psyllium.
Antidiarrheal agents can precipitate toxic megacolon and should be avoided.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 76, “Disorders Presenting Primarily with Diarrhea,” by Nicholas E. Kman and Howard A. Werman.