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484 SECTION 9: Gastrointestinal Disorders Disorders Presenting Primarily With Diarrhea Nicholas E. Kman Howard A. Werman Sarah M. Greenberger GENERAL ASSESSMENT OF PATIENTS WITH DIARRHEA  INTRODUCTION AND EPIDEMIOLOGY This chapter discusses the general assessment of patients with diarrhea and the special considerations of acute infectious and traveler’s diarrhea, Clostridium difficile diarrhea and colitis, inflammatory bowel disease, ileitis and colitis, and ulcerative colitis. Acute diarrhea is the sudden onset of an increase in the normal water content of stool. In general, humans lose approximately 10 mL/kg/d of fluids in stool. The increased water content of diarrhea results in an increased frequency of stools from three or more times daily to more than 20 bowel movements in a 24-hour period. Diarrhea is an increased propranolol, and topiramate. Mitochondrial-targeted therapies such as L-carnitine, coenzyme Q10, and riboflavin have shown excellent efficacy in combination with amitriptyline and alone. REFERENCES The complete reference list is available online at www.TintinalliEM.com. TABLE 72-3 Antiemetic Agents for the Treatment of Nausea and Vomiting Medication Class Route Common Side Effects Comments Antihistamines Dimenhydrinate (Dramamine® ) Diphenhydramine (Benadryl® )* Meclizine (Antivert® ) IV, IM, PO Drowsiness Also show efficacy in prevention of motion sickness. Useful for migraines and vertigo. Used in migraines and vertigo, which are vestibular in origin. Benzodiazepines Alprazolam (Xanax® ) Diazepam (Valium® ) Lorazepam (Ativan® ) PO, IV, PR PO, IV, IM Sedation Adjunct for chemotherapy-induced nausea and vomiting. Butyrophenones Haloperidol (Haldol® )* PO, IM Agitation, restlessness, sedation Treatment of acute chemotherapy-induced symptoms; can prolong QT Corticosteroids Dexamethasone PO, IV, IM Insomnia Used as an adjunct in severe cases of chemotherapy-induced nausea and vomiting; reduces prostaglandin formation. Serotonin antagonists Ondansetron (Zofran® )* Granisetron (Kytril® )* Dolasetron (Anzemet® )* PO, IV, SL PO, IV PO, IV Constipation, dizziness Well tolerated; all serotonin antagonists can prolong QT c in electrolyte- or drug-induced or congenital long QTc syndrome; uncommon side effects include headache; rare case reports of anaphylaxis. Phenothiazines Prochlorperazine (Compazine® )† Promethazine (Phenergan® )†

PO, IV, SL PO, IV PO, IV Constipation, dizziness Well tolerated; all serotonin antagonists can prolong QT c in electrolyte- or drug-induced or congenital long QTc syndrome; uncommon side effects include headache; rare case reports of anaphylaxis. Phenothiazines Prochlorperazine (Compazine® )† Promethazine (Phenergan® )† PO, IV, IM, PR PO, IV, IM, PR Extrapyramidal symptoms, ‡ sedation, orthostatic hypotension Treatment in migraines, vertigo, and motion sickness; rare side effects include neuroleptic malignant syndrome, blood dyscrasias, and cholestatic jaundice. Benzamides Metoclopramide (Reglan® ) Trimethobenzamide (Tigan® )

PO, IV, SL PO, IV PO, IV Constipation, dizziness Well tolerated; all serotonin antagonists can prolong QT c in electrolyte- or drug-induced or congenital long QTc syndrome; uncommon side effects include headache; rare case reports of anaphylaxis. Phenothiazines Prochlorperazine (Compazine® )† Promethazine (Phenergan® )† PO, IV, IM, PR PO, IV, IM, PR Extrapyramidal symptoms, ‡ sedation, orthostatic hypotension Treatment in migraines, vertigo, and motion sickness; rare side effects include neuroleptic malignant syndrome, blood dyscrasias, and cholestatic jaundice. Benzamides Metoclopramide (Reglan® ) Trimethobenzamide (Tigan® ) PO, IV, IM PO, IM Extrapyramidal symptoms, ‡ hyperprolactinemia Used in treatment of gastroparesis and children with reflux. *QT interval prolongation reported. †Nonspecific Q or T distortions reported. ‡Extrapyramidal symptoms: dystonia, tardive dyskinesia, oculogyric crisis, parkinsonism. CHAPTER frequency of defecation, usually greater than three bowel movements per day for a daily stool weight exceeding 250 grams.1 Practically speaking, however, diarrhea is present when the patient is making more stools of lesser consistency more frequently.  PATHOPHYSIOLOGY There are four basic mechanisms of diarrhea: increased intestinal secretion, decreased intestinal absorption, increased osmotic load, and abnormal intestinal motility. Normally, the jejunum receives between 6 and 8 L per day of fluid in the form of oral intake and gastric, pancreatic, and biliary secretions. Dietary intake actually constitutes a small por tion of the jejunal load (1.5 L). A healthy small intestine absorbs nearly 75% of the fluid to which it is exposed. The 2 L of fluid not absorbed by the small intestine then enters the colon, where fluid is absorbed at an even higher rate. The absorptive power of the colon approaches 90% efficiency and far exceeds that of the small intestine. In fact, the colon can make up for a decrease in small intestinal absorption. Under normal conditions, very little fluid (<100 mL) is lost in the stool each day. In diarrheal states, normal intestinal physiology is disrupted. At a cellular level, intestinal absorption occurs through the villi, and secretion occurs through the crypts. Fluids are absorbed by two mechanisms: passively with the transport of sodium and actively with the absorption of glucose. Selected enterotoxins block the passive sodium resorption and specifically stimulate sodium excretion, resulting in a net loss of fluid. The glucose-dependent mechanism of water absorption, however, is unaffected by these toxins and can be exploited by including glucose in the rehydration treatments. The composition of oral rehydration therapies recommended by the World Health Organization is based largely on this physiology. In addition, diarrheal states, enterotoxins, inflammation, or ischemia disrupt the structure of the intestinal villi preferentially with less involvement in the crypts. As a result, diarrhea occurs because of diminished intestinal villi absorption and unopposed crypt secretion (the crypts are more resilient after injury). Another mechanism by which disease processes cause diarrhea is by the delivery of an osmotic load to the intestine. For example, Tintinalli_Sec09_p0473-0562.indd 484 8/2/19 6:49 PM

arrhea occurs because of diminished intestinal villi absorption and unopposed crypt secretion (the crypts are more resilient after injury). Another mechanism by which disease processes cause diarrhea is by the delivery of an osmotic load to the intestine. For example, Tintinalli_Sec09_p0473-0562.indd 484 8/2/19 6:49 PM CHAPTER 73: Disorders Presenting Primarily With Diarrhea 485 administration of a laxative results in the collection of an osmotically active, nondigestible agent within the intestinal lumen. Other substances such as diet products and medications (e.g., colchicine) have similar effects. Osmosis occurs, drawing fluid into the intestinal lumen, and results in diarrhea. Increased intestinal motility also causes diarrhea. This mechanism is responsible for diarrhea in patients with irritable bowel syndrome, neuropathies, or a shortened intestine secondary to surgery. Diarrheal illness is primarily a viral infection (norovirus) but can also be caused by bacteria and parasites. Antibiotic and nosocomial diarrhea is most often caused by C. difficile. Many drugs affect gastrointestinal function. Erythromycin accelerates gastric emptying. Clavulanate stimulates small bowel motility. Other drugs that cause diarrhea are laxatives, sorbitol, lactose, nonsteroidal anti-inflammatory drugs, and cholinergics. Inflammatory bowel disease, ulcerative colitis, and Crohn’s disease are characterized by diarrhea. If patients have fecal evidence of inflammation and Shigella, Salmonella, Campylobacter, C. difficile, or Entamoeba histolytica have been excluded, suspect inflammatory bowel disease. Less common causes of severe diarrhea include GI bleeding, thyrotoxicosis, toxin exposure, and mesenteric ischemia, which are addressed elsewhere in the text.  CLINICAL FEATURES History After confirming a diarrheal illness, focus on identifying the cause. Determine whether the diarrhea is acute (<3 weeks) or chronic (>3 weeks). The acute diarrheas are of greatest concern to the emergency physician as they are more apt to be a manifestation of an immediately life-threatening illness (infection, ischemia, intoxication, or inflammation). In the United States, most infectious diarrheal illnesses are caused by noroviruses or rotaviruses and occur in the winter. Ask directed questions to characterize the diarrhea: Is the diarrhea bloody or melenic? Is it associated with possible food poisoning or the ingestion of certain foods, such as milk or sorbitol? Does it resolve or persist with fasting? If so, this can indicate an osmotic or secretory diarrhea, respectively. Are the stools of smaller volume, localizing to the large intestine, or of larger volume, indicating small intestine pathology? What symptoms accompany the diarrhea? Is there fever or abdominal pain, which may suggest diverticulitis, infectious gastroenteritis, or inflammatory bowel disease? Seizures accompanying diarrhea often point toward shigellosis but could also indicate theophylline toxicity or hyponatremia. Does the patient have heat intolerance and anxiety, suggesting thyrotoxicosis, or paresthesias and reverse temperature sensation, suggesting ciguatera poisoning? Next, define the host by obtaining the medical and surgical history. The differential diagnosis for diarrhea is broadened if the patient is immunocompromised. Is the patient taking medication that may cause diarrhea? Has the patient recently traveled outside the United States or to a rural area? Rural hiking places the patient at risk for Giardia, particularly if water-purification procedures were not strictly followed, and travel to developing countries increases the chances of parasitic infection and traveler’s diarrhea. A patient’s occupation may be a clue to a diagnosis of organophosphate poisoning.

area? Rural hiking places the patient at risk for Giardia, particularly if water-purification procedures were not strictly followed, and travel to developing countries increases the chances of parasitic infection and traveler’s diarrhea. A patient’s occupation may be a clue to a diagnosis of organophosphate poisoning. Physical Examination Some examination findings helpful for diagnosis include thyroid enlargement, masses, oral ulcers, erythema nodosum, episcleritis, or an anal fissure, which would point toward inflammatory bowel disease. Reiter’s syndrome, the triad of arthritis, conjunctivitis, and urethritis or cervicitis, should cause concern for Salmonella, Shigella, Campylobacter, or Yersinia infection. Abdominal and rectal examinations are critical. Especially in the elderly, fecal impaction may result in diarrhea as liquid stool passes around the impaction. Pay attention to the presence or absence of surgical scars, tenderness, masses, or peritoneal signs. Check the stool for blood, because bloody diarrhea can be caused by inflammation, infection, or ischemia. An elderly patient with bloody diarrhea and abdominal pain out of proportion to the physical examination may have mesenteric ischemia—a true emergency.  DIAGNOSTIC STOOL EVALUATION Diagnostic testing is rarely immediately helpful in the ED, but it can be helpful at patient follow-up. Since most diarrheal illnesses are selflimited, viral, or last less than 24 hours, most patients who present within 24 hours of onset need no microbiologic examination. Patients who have severe abdominal pain, fever, and diarrhea that is voluminous, purulent, or bloody may have acute infectious diarrhea associated with the following pathogens: Salmonella , Campylobacter, Shigella, Shiga toxin–producing Escherichia coli, Ye r si ni a, Vibrio, or C. difficile. Patients fitting this subset will require microbiologic evaluation, as described next. In the past, authors have described Wright’s stain for fecal leukocytes and ova and parasite evaluation of the stool. These are not included as they have poor sensitivity and specificity and better tests have emerged. Bacterial Stool Culture Bacterial stool culture is expensive and labor intensive and plays a minor role in the ED evaluation of diarrhea. The diagnostic yield of stool cultures is probably <5%, unless there is careful patient selection. 1 Obtain stool cultures for bacteria in ill children; toxic, dehydrated, or febrile patients; patients with a diarrheal illness >3 days; patients with blood or pus in the stool; and the immunocompromised. For systemic illness, fever, or bloody stools, test for Salmonella, Shigella, Campylobacter, Shiga toxin–producing E. coli, or amoebic infection. Most laboratories are capable of detecting Shigella, Salmonella, Campylobacter, Shiga toxin–producing E. coli O157:H7 strains, Giardia, Cryptosporidium, E. histolytica, and rotavirus. In patients with persistent diarrhea due to a presumed parasitic infection, three separate stool samples should be collected to detect the causative organism. Clostridium difficile Toxin Assay C. difficile infection is the most common cause of antibiotic-associated or nosocomial diarrhea. Diagnosis is by the C. difficile toxin assay. Unfortunately, this assay has a 10% falsenegative rate, and the current recommendation is to include other testing such as glutamate dehydrogenase detection along with nucleic acid amplification testing to confirm the diagnosis. 5,10 Other Diagnostic Tests If diarrhea is not infectious in origin, data acquisition should be dictated by the differential diagnosis. Severely dehydrated patients need serum electrolyte and renal function measurements. Serum drug levels can assist the physician in making the diag nosis of theophylline, lithium, or heavy metal intoxication.

ests If diarrhea is not infectious in origin, data acquisition should be dictated by the differential diagnosis. Severely dehydrated patients need serum electrolyte and renal function measurements. Serum drug levels can assist the physician in making the diag nosis of theophylline, lithium, or heavy metal intoxication. In patients with a history of abdominal surgery, abdominal films may help rule out partial obstruction as a cause of diarrhea. A chest radiograph may help diagnose Legionella pneumonia in a patient with diarrhea and a cough. For patients in whom mesenteric ischemia is suspected, obtain a serum lactate, IV contrast CT scan, or mesenteric angiography.  TREATMENT Severely dehydrated patients need IV hydration. Oral rehydration with a glucose-based electrolyte solution can be initiated in patients without associated nausea or vomiting and without severe dehydration. Glucosecontaining, caffeine-free beverages are the fluids of choice. The glucose transport mechanism is unaffected by enterotoxins, allowing for water absorption in the small intestine. For patients who can afford to buy it, Gatorade ® is a good rehydration choice for patients with mild dehydra tion. The World Health Organization recommends a solution with a higher sodium concentration for more extensive dehydration. Ingestion of 400 to 600 mL/h may be needed to treat dehydration and keep up with stool fluid losses in severe diarrhea. Nausea and vomiting should be treated because they may compromise oral rehydration therapy. Counsel patients to avoid caffeine, which stimulates gastric motility, and sorbitol-containing chewing gum or raw fruits, which can worsen osmotic diarrhea. Initially, avoid lactose until the colonic villi are able to recover and produce the necessary digestive enzymes. Encourage patients to attempt early solid food intake, but with the previously mentioned restrictions, because eating expedites the recovery from diarrheal illnesses. ACUTE INFECTIOUS AND TRAVELER’S DIARRHEA  INTRODUCTION AND EPIDEMIOLOGY Viruses cause the vast majority of infectious diarrheas, followed by bacterial and parasitic organisms. Norovirus causes 50% to 80% of all infectious diarrhea in the United States, followed with much less fre quency by non–Shiga toxin–producing E. coli, C. difficile, invasive bacteria, Shiga toxin–producing E. coli, and protozoa. 1,4 Tintinalli_Sec09_p0473-0562.indd 485 8/2/19 6:49 PM

y bacterial and parasitic organisms. Norovirus causes 50% to 80% of all infectious diarrhea in the United States, followed with much less fre quency by non–Shiga toxin–producing E. coli, C. difficile, invasive bacteria, Shiga toxin–producing E. coli, and protozoa. 1,4 Tintinalli_Sec09_p0473-0562.indd 485 8/2/19 6:49 PM 486 SECTION 9: Gastrointestinal Disorders The incidence of traveler’s diarrhea during a 2-week trip remains 10% to 40%, depending on destination and traveler. Improved hygiene and awareness have reduced the risk of traveler’s diarrhea in many destinations. 7 The most important risk factor for traveler’s diarrhea is the destination of travel, with the risk increasing with travel to areas of lower socioeconomic status. South Asia and West and Central Africa remain the destinations with the highest risk of traveler’s diar rhea. Decreasing rates are being seen in South America and East and Southeast Asia. 7 Other risk factors include the level of food contami nation, the season of travel (rainy seasons are associated with a higher risk of traveler’s diarrhea), use of a proton pump inhibitor, previous contraction of traveler’s diarrhea (suggests genetic susceptibility), and the type of travel (adventure travel, camping, backpacking, and living with native inhabitants are associated with higher risk). 8 The major bacteria responsible are the toxin- and non–toxin-producing strains of E. coli. These strains of E. coli make up most identifiable cases in Mexico and South America. The invasive bacteria, such as Campylobacter jejuni, Shigella, and S almonella, are more commonly seen in travelers to southern Asia.  CLINICAL FEATURES The presence of severe abdominal pain, fever, or bloody stool requires microbiologic studies to rule out bacterial or amoebic infection. Laboratory Testing Obtain stool culture for Salmonella, Shigella, Campylobacter, and E. coli O157:H7; assay for Shiga toxin; and micros copy or antigen assay for E. histolytica.3 Exposure of a traveler or hiker to untreated water and illness that persists for more than 7 days should prompt evaluations for protozoal pathogens. Test stool for E. histolytica antigen, Giardia intestinalis antigen, and Cryptosporidium parvum antigen by enzyme immunoassay. Rarely, helminthes such as Ascaris, Enterobius, and Strongyloides have been implicated.  TREATMENT Treatment of infectious diarrhea includes antibiotics, antimotility agents, restoration of fluid balance, and avoidance of agents that worsen diarrhea (Table 73-1). Loperamide and antibiotics improve outcome. Antibiotics shorten the duration of illness by about 24 hours. 1 Even though most cases of infectious diarrhea are self-limited, because of the inconveniencing and debilitating nature of the disease, we recommend ciprofloxacin treatment for all patients believed to have an infec tious diarrhea who do not have a contraindication to the drug (e.g., children, allergy, pregnancy, or drug interaction). There are reports of growing fluoroquinolone resistance in bacterial pathogens. 7 Concerns remain about the impact of ciprofloxacin on the intestinal flora 9 and its side effect profile, and other non–GI-absorbed agents such as rifaximin are an option. 11 (See Table 73-2 for specific treatments.) Loperamide shortens the duration of symptoms when combined with an antibiotic regimen. Loperamide, bismuth subsalicylate, and kaolin are the only agents that are labeled as antidiarrheals. Do not use antimotility agents in the subset of patients with bloody diarrhea or suspected inflammatory diarrhea because of the possibility of prolonged fever, toxic megacolon in C. difficile patients, and hemolytic uremic syndrome in children infected with Shiga toxin–producing E. coli.

are labeled as antidiarrheals. Do not use antimotility agents in the subset of patients with bloody diarrhea or suspected inflammatory diarrhea because of the possibility of prolonged fever, toxic megacolon in C. difficile patients, and hemolytic uremic syndrome in children infected with Shiga toxin–producing E. coli. Probiotics are safe and beneficial when used alongside rehydration therapy.12 Proton pump inhibitors are not effective.9  DISPOSITION Admit the toxic patient and any patient who cannot comply with oral rehydration. Be conservative in admitting those at extremes of age. Most patients with diarrhea can be discharged home. The best way to combat many infectious diarrheas is with preven tion. Counsel families about frequent hand washing to minimize spread of disease and about the proper selection and preparation of food and beverages consumed while traveling as a cornerstone of prevention. Encourage the use of boiled, bottled, and carbonated water for drinking, brushing teeth, and preparing food and infant formula. Water can be made safe by boiling, treating it chemically, or filtering. 7 A quick phrase for prevention is, “Peel it, boil it, cook it, or forget it!” In addition, vaccines against the most common etiologic agent, rota virus, are now available.13 Provide work excuses for patients employed in the food, day-care, and healthcare industries. CLOSTRIDIUM DIFFICILE–ASSOCIATED DIARRHEA AND COLITIS  INTRODUCTION AND EPIDEMIOLOGY C. difficile is a spore-forming obligate anaerobic bacillus that causes infection ranging from mild diarrhea to severe pseudomembranous colitis. The frequency of C. difficile infection increased from 4.5 cases per 1000 discharges in 2001 to 8.2 in 2010, with a mortality rate of approximately 7%. 14 Although many cases are found among hospitalized adults, up to one third of cases occur in the community. A more virulent TABLE 73-1 Empiric Treatment of Traveler’s Diarrhea in the Adult Rehydration Fluids: chicken broth with fruit juices, Gatorade® , noncaffeinated sodas, packages of salts and glucose to be reconstituted with boiled or treated water, CeraLyte 90 ® , Pedialyte® Foods: complex carbohydrates (bananas, bread, rice, apple juice, and tortillas), potatoes, crackers, Lactobacillus-containing yogurt Trade Name Dosage Comments Antimotility Agents Bismuth subsalicylate Pepto-Bismol® 30 mL or 2 tablets every 30 min for 8 doses; repeat on day 2 Salicylate toxicity may occur with excessive dosing; may cause bismuth encephalopathy in HIV-positive patients. Loperamide Imodium® 4 milligrams initially, then 2 milligrams after each unformed stool for no more than 2 days; maximum, 16 milligrams per day Preferred first-line agent for antimotility, with minimal central opiate effects. Can be used with antibiotics. Diphenoxylate and atropine Lomotil® 4 milligrams four times a day for 2 days Second-line agent with more central opiate effects (narcotic related to meperidine); may potentiate the action of barbiturates, tranquilizers, and alcohol. Antibiotics Ciprofloxacin Cipro® 500 milligrams single dose or 500 milligrams twice a day for 3 days For moderately severe illness in adults; complete 3-day course if single dose fails; significant drug–drug interactions may occur. Often first choice for use except in South and Southeast Asia. Azithromycin Zithromax® 1000 milligrams in a single dose First choice for use in South and Southeast Asia. Safe for children and pregnant women. Rifaximin11 Xifaxan® , Salix® 200 milligrams PO three times daily for 3 days For moderately severe illness; do not use for fever or bloody stools; class C in pregnancy. Abbreviation: HIV = human immunodeficiency virus. Tintinalli_Sec09_p0473-0562.indd 486 8/2/19 6:49 PM

heast Asia. Safe for children and pregnant women. Rifaximin11 Xifaxan® , Salix® 200 milligrams PO three times daily for 3 days For moderately severe illness; do not use for fever or bloody stools; class C in pregnancy. Abbreviation: HIV = human immunodeficiency virus. Tintinalli_Sec09_p0473-0562.indd 486 8/2/19 6:49 PM CHAPTER 73: Disorders Presenting Primarily With Diarrhea 487 TABLE 73-2 Antimicrobial Recommendations for Infectious Pathogens in Adults Organism Primary Treatment Alternative Treatment Empiric treatment—but not for bloody diarrhea; not for Shiga toxin E. coli 0157:H7 Ciprofloxacin 500 milligrams PO twice a day for 5 days Trimethoprim-sulfamethoxazole DS, 1 tab PO twice a day for 5 days C. difficile Vancomycin 125 milligrams PO 4 times a day for 10 days Fidaxomicin, 200 milligrams PO two times a day for 10 days E. coli 0157:H7 No antibiotics No antibiotics Listeria monocytogenes No antibiotics No antibiotics Yersinia No antibiotics; usually self-limited Ciprofloxacin 500 milligrams PO twice a day for 3 days; or trimethoprim-sulfamethoxazole DS, 1 tab PO twice a day for 3 days Salmonella non-typhi Ciprofloxacin 750 milligrams PO twice a day for 5 days Azithromycin 500 milligrams PO once a day for 7 days Shigella Ciprofloxacin 750 milligrams PO twice a day for 3 days Azithromycin 500 milligrams PO once a day for 3 days V. cholerae Doxycycline 500 milligrams PO for one dose Azithromycin 1 gram PO for one dose Trimethoprim-sulfamethoxazole DS, 1 tab PO twice a day for 3 days E. histolytica Metronidazole 750 milligrams PO three times a day for 10 days AND paromomycin 10 milligrams/kg three times a day PO for 7 days Metronidazole AND iodoquinol 650 milligrams PO three times a day for 20 days Tinidazole 2 grams PO once a day for 3 days AND paromomycin or iodoquinol Cyclospora Trimethoprim-sulfamethoxazole DS, 1 tab PO twice a day for 10 days Giardia Tinidazole 2 grams PO for one dose Nitazoxanide 500 milligrams PO twice a day for 3 days Metronidazole 750 milligrams PO three times a day for 10 days Paromomycin 10 milligrams/kg/d PO three times a day for 10 days Note: Length of treatment often varies with different sources. strain of C. difficile called B1/NAP1/027 causes more severe disease that often progresses to toxic megacolon. The organism secretes two toxins, A and B, that cause a secretory diarrhea. At the most severe end of the spectrum, three different syndromes have been described: neonatal pseudomembranous enterocolitis, post operative pseudomembranous enterocolitis, and antibiotic-associated pseudomembranous colitis. In pseudomembranous colitis, membranelike yellowish exudative plaques overlie and replace necrotic intestinal mucosa. A pseudomembrane is present in only 50% of laboratoryconfirmed cases of C. difficile colitis. Recent antibiotic use, GI surgery or manipulation, severe underlying medical illness, chemotherapy, gastric acid suppression with proton pump inhibitors or H 2 blockers, and advancing age are risk factors for pseudomembranous colitis. Transmission of the organism is by direct human contact as well as contact with inanimate objects (commodes, telephones, rectal thermometers).  PATHOPHYSIOLOGY Hospitalized patients are colonized with C. difficile in 20% to 50% of cases, so the development of diarrhea in recently discharged patients is suggestive of C. difficile infection. There is a linear relationship between the length of hospital stay, colonization with C. difficile, and the development of C. difficile diarrhea. Up to 70% of residents of long-term health facilities are C. difficile carriers. Broad-spectrum antibiotics reduce fecal anaerobes, which are needed for carbohydrate metabolism and bile acid breakdown.

hip between the length of hospital stay, colonization with C. difficile, and the development of C. difficile diarrhea. Up to 70% of residents of long-term health facilities are C. difficile carriers. Broad-spectrum antibiotics reduce fecal anaerobes, which are needed for carbohydrate metabolism and bile acid breakdown. One study ranked cephalosporins, clindamycin, carbapenems, trimethoprim/sulfonamides, fluoroquinolones, and penicillin combinations as the most frequent offenders. 15 Accumulation of gut carbohydrates can cause osmotic diarrhea, and the accumulation of bile acids, which are colonic secretory agents, also results in diarrhea. Toxin-producing C. difficile then flourishes within the colon. Almost any antibiotic (including metronidazole and vancomycin) can lead to pseudomembranous colitis, and chemotherapeutic agents, proton pump inhibitors, and antiviral agents have also been implicated. Bowel ischemia, inflammatory bowel disease, recent bowel surgery, uremia, malnutrition, shock, advanced age, peripartum status, and Hirschsprung’s disease also contribute to the development of C. difficile infection and pseudomembranous colitis. Probiotics have been implicated in reducing the incidence of C. difficile infection if taken concomitantly with antibiotics but have no role in treating active or recurrent disease. Most disease-producing strains of C. difficile produce two toxins— toxin A, an enterotoxin, and toxin B, a cytotoxin—that interact in a complex way to produce pseudomembranous colitis and its associated symptoms. B1/NAP1/027 produces a third (binary) toxin, contributing to its more virulent course.  CLINICAL FEATURES The disease typically begins 7 to 10 days after the institution of anti biotic therapy, although symptoms may occur up to 60 days after the antibiotic is discontinued. C. difficile colitis results in a spectrum of clinical manifestations that vary from frequent, mucoid, watery stools to a toxic picture that includes profuse diarrhea (20 to 30 stools per day), crampy abdominal pain, fever, leukocytosis, and dehydration. Stool examination may demonstrate fecal leukocytes, which are not generally found in more benign forms of antibiotic-induced diarrhea. In 3% of patients, toxic megacolon or colonic perforation may occur in patients with pseudomembranous colitis.  DIAGNOSIS The diagnosis is suggested by a history of diarrhea that develops during administration of antibiotics or within 2 weeks of their discontinuation. The patient should experience a minimum of three unformed stools in a 24-hour period to be considered as having an active infection. Stool Assays Cell culture cytotoxicity assays remain the “gold stan dard” but take up to 48 hours for results. The organism is best identified by stool culture using a selective growth medium. This technique has a sensitivity approaching 100% but lacks specificity because the presence of C. difficile does not necessarily implicate it in the cause of the disease. Instead, C. difficile toxins are detected directly using a number of techniques including enzyme-linked immunosorbent assays, latex Tintinalli_Sec09_p0473-0562.indd 487 8/2/19 6:49 PM

proaching 100% but lacks specificity because the presence of C. difficile does not necessarily implicate it in the cause of the disease. Instead, C. difficile toxins are detected directly using a number of techniques including enzyme-linked immunosorbent assays, latex Tintinalli_Sec09_p0473-0562.indd 487 8/2/19 6:49 PM 488 SECTION 9: Gastrointestinal Disorders agglutination, dot-immunobinding assays, and polymerase chain reac tion. Tests vary in their sensitivity, specificity, and time to completion. Many laboratories are using polymerase chain reaction technology, which has excellent sensitivity (71% to 100%) and specificity (73% to 100%) 16 and rapid test turnaround, usually within 1 hour. 17 As noted, confirmatory testing should be included in establishing the diagnosis.5 Colonoscopy Colonoscopy reveals characteristic yellowish plaques within the intestinal lumen. Lesions may be seen throughout the entire alimentary tract, although they are typically limited to the right colon. Colonoscopy is not routinely needed to establish a diagnosis and carries the risk of perforation in severe colitis but may be used in patients who require a rapid diagnosis and those who cannot produce a stool speci men due to ileus or in whom the initial assay is negative.  TREATMENT Mild C. difficile infection in an otherwise healthy patient is treated by discontinuing the offending antibiotic. This is effective in only about 20% of cases, however. Severely ill persons must be hospitalized. For specific antibiotic regimens, see Table 73-3. Fidaxomicin (macrolide antibiotic) 200 milligrams PO twice a day for 10 days has replaced met ronidazole as a primary agent. Rarely, emergency colectomy may be required for patients with severe C. difficile infection. Indications for emergency colectomy based on 30-day mortality include leukocytosis >20,000 mm 3, lactate >5 mmol/L, age >75 years, immunosuppression, shock, toxic megacolon, colonic perforation, rapidly progressive disease, or multiorgan system failure. This procedure carries a high mortality rate. Recently, creation of a loop ileostomy with colonic lavage has been reported to be an effective surgical approach. Relapses occur in 20% to 30% of patients. Patients with prolonged antibiotic use, prolonged hospitalization, advanced age, diverticulosis, or multiple comorbidities are at increased risk for relapse. The addition of monoclonal antibodies against the toxin to antibiotics reduces infection recurrence. 18 The use of antidiarrheal agents is contraindicated. Steroids are rarely needed. Finally, fecal microbiota transfer has emerged as a therapy for refractory cases of recurrence. Ensure contact isolation, use of personal protective equipment, and good hand washing with soap and water when caring for patients with suspected C. difficile–associated disease. Alcohol-based rubs are not effective in eliminating the spores of C. difficile.  DISPOSITION Hospitalize patients with severe diarrhea, clinical toxicity, or symptoms that persist despite appropriate outpatient management. Consult the surgeon for acutely ill patients with C. difficile infection, especially those with suspected toxic megacolon or intestinal perforation for con sideration of colectomy. For patients who are discharged, discontinue antibiotics and encourage good oral hydration. Follow the antibiotic recommendations in Table 73-3. INFLAMMATORY BOWEL DISEASE/ILEITIS/ COLITIS/CROHN’S DISEASE  INTRODUCTION AND EPIDEMIOLOGY Crohn’s disease is a chronic granulomatous inflammatory disease of the GI tract of unknown origin, but genetic and environmental factors have been implicated in causing the disease. Crohn’s disease can involve any part of the GI tract from the mouth to the anus. The ileum is involved in the majority of cases.

DEMIOLOGY Crohn’s disease is a chronic granulomatous inflammatory disease of the GI tract of unknown origin, but genetic and environmental factors have been implicated in causing the disease. Crohn’s disease can involve any part of the GI tract from the mouth to the anus. The ileum is involved in the majority of cases. In 20%, the disease is confined to the colon, making differentiation from ulcerative colitis difficult. The terms regional enteritis, terminal ileitis, granulomatous ileocolitis, and Crohn’s disease are all used to describe the same disease process. The peak incidence of Crohn’s disease occurs between 15 and 22 years of age, with a secondary peak from 55 to 60 years. The incidence has remained steady in the past several years. The disease is four times more common among Jews than non-Jews and is more common in whites than blacks, Asians, or Native Americans. A family history of inflam matory bowel disease is present in 10% to 15% of patients, particularly with early onset of disease. Ulcerative colitis as well as Crohn’s disease may be present in other family members, and siblings of patients with Crohn’s disease have a higher incidence of the disease. Smoking, oral contraceptive use, and the use of nonsteroidal anti-inflammatory agents worsen the course of the disease. Smoking is also associated with a twofold increased risk of developing Crohn’s disease.  PATHOPHYSIOLOGY The most important pathologic feature of Crohn’s disease is the involvement of all the layers of the bowel and extension into mesenteric lymph nodes. The disease is discontinuous, with normal areas of bowel (“skip areas”) located between one or more involved areas. Longitudinal, deep mucosal ulcerations are characteristic. If ulcerations penetrate the bowel wall, fissures, fistulas, and abscesses result. Late in the disease, a cobblestone appearance of the mucosa results from the criss-crossing of ulcers with intervening normal mucosa.  CLINICAL FEATURES Patients presenting to the ED do so because of chronic symptoms such as abdominal pain and weight loss that remain undiagnosed, acute flares in patients with known disease, and most commonly, complications of Crohn’s disease. Occasionally, side effects and complications of therapy bring the patient to the ED. The clinical course of Crohn’s disease varies and in the individual patient is unpredictable. There are three general types of Crohn’s presentations: inflammatory, stricturing, and penetrating disease. The disease is classified as mild, moderate, and severe based on the Clinical Disease Activity Index. 20 Abdominal pain, anorexia, diarrhea, and weight loss are present in most cases.

al patient is unpredictable. There are three general types of Crohn’s presentations: inflammatory, stricturing, and penetrating disease. The disease is classified as mild, moderate, and severe based on the Clinical Disease Activity Index. 20 Abdominal pain, anorexia, diarrhea, and weight loss are present in most cases. Chronic abdominal pain, weight loss, fever, and diarrhea may be present for several years before definitive diagnosis is TABLE 73-3 Treatment of Clostridium difficile Infection Based on Severity of Illness5 Disease Severity Treatment Asymptomatic carrier No treatment Initial episode Discontinue inciting antibiotics Mild: WBC <15,000 mm3 Vancomycin 125 milligrams PO four times a day for 10 days Moderate: WBC >15,000 3, patient able to tolerate PO Fidaxomicin 200 milligrams PO twice daily for 10 days First relapse Fidaxomicin 200 milligrams twice daily for 10 days if vancomycin was used for the initial episode OR tapered and pulsed vancomycin regimen if a standard regimen was used for the initial episode (e.g., 125 milligrams four times per day for 10–14 days, two times per day for a week, once per day for a week, and then every 2 or 3 days for 2–8 weeks) Second relapse Tapered and pulsed vancomycin regimen of 125 milligrams four times per day for 10–14 days, two times per day for a week, once per day for a week, and then every 2 or 3 days for 2–8 weeks OR vancomycin 125 milligrams four times per day by mouth for 10 days followed by rifaximin 400 milligrams three times daily for 20 days OR fidaxomicin 200 milligrams given twice daily for 10 days Severe disease or complicated disease Vancomycin 500 milligrams IV or via nasogastric tube every 6 hours AND vancomycin 500 milligrams per rectum every 6 hours; also, metronidazole 500 milligrams IV every 8 hours or fecal microbiota transfer Note: Assume the offending antibiotic is discontinued. Source: Data from McDonald LC, Gerding DN, Johnson S, et al: Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA), Clin Infect Dis 2018 Mar 19;66(7):987-994.Tintinalli_Sec09_p0473-0562.indd 488 8/2/19 6:49 PM

son S, et al: Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA), Clin Infect Dis 2018 Mar 19;66(7):987-994.Tintinalli_Sec09_p0473-0562.indd 488 8/2/19 6:49 PM CHAPTER 73: Disorders Presenting Primarily With Diarrhea 489 established. Perianal fissures or fistulas, hematochezia, abscesses, or rectal prolapse can develop, particularly with colonic involvement. Patients may also present with complications of the disease, such as obstruction with vomiting, crampy abdominal pain, and obstipation, or an intraabdominal abscess with fever, abdominal pain, and a palpable mass. In children with Crohn’s disease and ulcerative colitis, growth retardation and delay in the onset of puberty are prominent. In 10% to 20% of patients, the extraintestinal manifestations of arthritis, uveitis, or liver disease may be presenting symptoms. Crohn’s disease should also be considered in the differential diagnosis of patients with fever of unknown etiology. The incidence of stroke, ischemic heart disease, chronic obstructive pulmonary disease, and thromboembolic disease is increased in patients with inflammatory bowel disease and should be considered when such patients present to the ED. The clinical course and manifestations of the disease appear to be related to its anatomic distribution: in 30%, the disease involves only the small bowel; in 20%, only the colon is involved; and in 50%, both the small bowel and colon are involved. A small percentage of patients present with disease involving the mouth, esophagus, and stomach. Crohn’s disease of the stomach may cause symptoms of dyspepsia. Extraintestinal manifestations are seen in up to 50% of patients with Crohn’s disease (Table 73-4), The types of extraintestinal complica tions are similar in patients with Crohn’s disease and ulcerative colitis, although they are most commonly seen in Crohn’s disease patients with colonic involvement.  DIAGNOSIS In most patients, the definitive diagnosis of Crohn’s disease is established months or years after symptom onset. A provisional diagnosis of appendicitis or pelvic inflammatory disease may change to Crohn’s disease after imaging or at the time of surgery. A detailed history asking about previous bowel symptoms that preceded the onset of acute right lower quadrant pain provides clues to the correct diagnosis. ED evaluation focuses on determining the severity of the attack; identifying significant complications such as obstruction, intra-abdominal abscess, life-threatening hemorrhage, or toxic megacolon; and eliminating other possible causes of the patient’s complaints. Laboratory Testing Laboratory evaluation should include a CBC, serum electrolytes, BUN, creatinine, and a type and cross-match where appropriate. C-reactive protein levels and erythrocyte sedimentation rate can be obtained to monitor disease activity. Other studies should include electrolytes, calcium, and liver function studies. Fecal markers of inflammation (calprotectin and lactoferrin) are other markers of disease activity. 22 Anemia is common in Crohn’s disease and may be caused by iron deficiency, chronic disease, and vitamin B 12 deficiency. Stool cultures and C. difficile toxin can be obtained if diarrhea is a prominent symptom. Imaging Plain radiographs have essentially been replaced by abdomi nal and pelvic CT scanning with PO and IV contrast, which can identify bowel wall thickening, segmental narrowing, destruction of the normal mucosal pattern, mesenteric edema, fistulas, and abscesses, suggestive of Crohn’s disease.

a prominent symptom. Imaging Plain radiographs have essentially been replaced by abdomi nal and pelvic CT scanning with PO and IV contrast, which can identify bowel wall thickening, segmental narrowing, destruction of the normal mucosal pattern, mesenteric edema, fistulas, and abscesses, suggestive of Crohn’s disease. However, be vigilant about the cumulative radiation risk (severe exposure defined as lifetime accumulation of >50 mSv) in patients with inflammatory bowel disease . MRI has similar diagnostic accuracy as CT. MRI is more expensive and has limited availability but involves less radiation exposure and avoids the use of iodinated con trast. Additionally, pelvic MRI is the best modality for imaging perianal fistulae. Ultrasound can be used to identify bowel wall thickening in the small intestine and portions of the large bowel. It is the diagnostic modality of choice for biliary complications. Extraintestinal complica tions such as gallstones, renal calculi, sacroiliitis, and osteomyelitis can also be seen on CT scan. Diagnosis is confirmed by colonoscopy. TABLE 73-4 Common Extraintestinal Manifestations of Inflammatory Bowel Disease Manifestation Description Arthritic Peripheral arthritis Migratory monoarticular or polyarticular pain in peripheral joints (hip, knee, ankle, wrist) with effusion Ankylosing spondylitis Pain and stiffness of spine, hips, neck, and rib cage with limitation in truncal motion, loss of lumbar lordosis; decreased chest expansion and forward cervical flexion in advanced disease Sacroiliitis Low back pain with morning stiffness, relieved by exercise; progressive joint sclerosis Ocular Episcleritis Eye burning or itching without visual changes or pain; scleral and conjunctival hyperemia Uveitis Acute blurring of vision, photophobia and pain; perilimbic scleral injection Dermatologic Erythema nodosum Painful, red, raised nodules on extensor surfaces of arms or legs Pyoderma gangrenosum Ulcerative lesions with a necrotic center and violaceous skin typically found in pretibial region or trunk Hepatobiliary Cholelithiasis Varies from asymptomatic stones to right upper quadrant pain, fever, vomiting Fatty liver Mild right upper quadrant pain; hepatomegaly Pericholangitis Mild elevation in serum alkaline phosphatase, asymptomatic Chronic active hepatitis Autoimmune elevation of liver aminotransferase enzymes, may progress to cirrhosis Primary sclerosing cholangitis Pruritus progressing to jaundice, fatigue, and lethargy; laboratory findings vary from mild elevations of alkaline phosphatase to cirrhosis, portal hypertension, and liver failure; male predominance Cholangiocarcinoma Extrahepatic biliary mass, evidence of biliary obstruction, jaundice, right upper quadrant pain, fever, malaise Pancreatitis Varies from painless elevation of serum amylase to clinically apparent central abdominal pain radiating to back; may be associated with drugs such as azathioprine, 6-mercaptopurine, sulfasalazine, mesalamine, olsalazine, metronidazole Vascular Thromboembolic disease Symptoms of deep venous thrombosis and pulmonary emboli; portal vein, mesenteric vein, and hepatic venous thrombosis reported Other Malnutrition Fatigue, malaise, muscular wasting, cachexia Chronic anemia Fatigue, malaise, pallor, dyspnea; may be microcytic (blood loss), macrocytic (B 12 deficiency), or autoimmune hemolytic Nephrolithiasis Flank pain, nausea, vomiting, hematuria; stones result from increased dietary oxalate absorption (calcium oxalate stones) and dehydration (urate stones) Tintinalli_Sec09_p0473-0562.indd 489 8/2/19 6:49 PM

lor, dyspnea; may be microcytic (blood loss), macrocytic (B 12 deficiency), or autoimmune hemolytic Nephrolithiasis Flank pain, nausea, vomiting, hematuria; stones result from increased dietary oxalate absorption (calcium oxalate stones) and dehydration (urate stones) Tintinalli_Sec09_p0473-0562.indd 489 8/2/19 6:49 PM 490 SECTION 9: Gastrointestinal Disorders Differential Diagnosis The differential diagnosis of Crohn’s disease includes lymphoma, ileocecal amebiasis, sarcoidosis, deep chronic mycotic infections involving the GI tract, GI tuberculosis, Kaposi’s sarcoma, Campylobacter enteritis, and Y ersinia ileocolitis. Fortunately, most of these are uncommon conditions and can be differentiated by appropriate laboratory tests and imaging. Yersinia ileocolitis and Campylobacter enteritis may cause chronic abdominal pain and diar rhea similar to Crohn’s disease but can be diagnosed by appropriate stool cultures. It is not uncommon that a bout of acute bacterial diarrhea may uncover a diagnosis of inflammatory bowel disease. Acute ileitis should not be confused with Crohn’s disease. Y oung patients with acute ileitis usually recover without sequelae and should not undergo surgery. When Crohn’s disease is confined to the colon, ischemic bowel disease (particularly in the elderly) and pseudomembranous colitis as well as ulcerative colitis must be included in the differential diagnosis. Con comitant infection with C. difficile colitis is more common in patients with inflammatory bowel disease and is associated with refractory C. difficile infection and a greater incidence of surgery and disease flares in these patients. Some clinical guidelines call for C. difficile testing in any inflammatory bowel disease patient with a disease flare.  TREATMENT The aim of therapy for this incurable disease includes relief of symp toms, induction of remission, maintenance of remission, prevention of complications, optimizing timing of surgery, and maintenance of nutrition. Initial treatment ( Table 73-5) consists of adequate fluid resuscita tion and restoration of electrolyte balance. Place a nasogastric tube for obstruction, peritonitis, or toxic megacolon. Administer broad-spectrum antibiotics for fulminant colitis or peritonitis. Patients with severe disease should receive IV steroids such as hydrocortisone 300 milligrams per day or an equivalent dose of methylprednisolone (48 milligrams per day) or prednisolone (60 milligrams per day). Salicylates Sulfasalazine 3 to 5 grams per day is for mild to moderate Crohn’s disease. Sulfapyridine is a by-product of the colonic breakdown of sulfasalazine. Many of the toxic side effects of sulfasalazine (e.g., vomiting, anorexia, nausea, headache, diarrhea, epigastric distress, pancreatitis) are attributable to sulfapyridine. The active moiety in sulfasalazine is mesalamine. Many of the newer 5′-acetyl salicylic acid drugs feature a derivative of mesalamine without the sulfapyridine component. Oral mesalamine, rectal mesalamine, olsalazine, and balsalazide are first-line agents in treating Crohn’s dis ease. The mesalamine formulations are most effective in patients with colonic disease and particularly in those with mild disease. Corticosteroids Oral glucocorticoids such as prednisone (40 to 60 milligrams per day) have traditionally been reserved for more severely affected patients but are now used as induction therapy. An ilealreleased form of budesonide (9 milligrams per day) may be beneficial in inducing a remission in patients with ileal and right colon disease. Glu cocorticoids are not preferred for maintaining remission because of their complications, but 50% of patients may ultimately be steroid dependent.

as induction therapy. An ilealreleased form of budesonide (9 milligrams per day) may be beneficial in inducing a remission in patients with ileal and right colon disease. Glu cocorticoids are not preferred for maintaining remission because of their complications, but 50% of patients may ultimately be steroid dependent. Immunosuppressives Immunosuppressive drugs such as 6-mercaptopurine, azathioprine, and thioguanine are useful in maintenance, as steroid-sparing agents, in healing fistulas, and in patients in whom there are serious contraindications to surgery. 24 These agents have been associated with leukopenia, fever, hepatitis, and pancreatitis, necessitating the need for close follow-up, particularly during the initial phase of therapy. Parenteral methotrexate (25 milligrams per week) is considered third line and has been used following steroid and thiopurine metabolite failure. Antibiotics Antibiotics are first-line agents for perianal disease and help induce remission. Ciprofloxacin (500 to 1000 milligrams per day) induces remission in approximately 55% of cases. Metronidazole (750 to 1500 milligrams per day) is also effective for perianal complications and fistulous disease. Combination therapies with antibiotics and biologic agents (see next section) have produced dramatic improvements in response. Rifaximin is a broad-spectrum antibiotic that is not absorbed from the GI tract. Rifaximin 800 milligrams twice daily for 12 weeks is effective for mild to moderate disease. However, antibiotics raise con cerns about precipitating C. difficile colitis infection. Biologics Patients with medically resistant moderate to severe Crohn’s disease may benefit from the anti–tumor necrosis factor antibodies infliximab, adalimumab, and certolizumab pegol. These agents have been used to induce remission in patients who fail conventional therapy with steroids or 5-aminosalicylic acid and in patients with exclusively colonic disease. Additionally, biologics are particularly effective in cases of disease relapse and fistulizing disease. 25 Anti-adhesion therapies, natalizumab and vedolizumab, and the anti-interleukin agent ustekinumab have been used when anti–tumor necrosis factor agents fail. 16,26,27 All biologics increase the risk of infections, especially those caused by hepatitis B and tuberculosis. Both immediate and delayed hypersensi tivity reactions are possible, especially with infliximab. Concern about the emergence of lymphomas and progressive multifocal leukoencephalopathy, especially with natalizumab, has limited the long-term use of these agents. Maintenance therapy and the effectiveness of various therapeutic agents in Crohn’s disease are variable. A reduced dose of 5-aminosalicyclic acid derivatives is used for the maintenance of remission of colonic disease. The addition of sulfasalazine, azathioprine, and 6-mercapto purine to prednisone does not improve the response rate and increases side effects. Infliximab or adalimumab and an immunosuppressive (azathioprine, 6-mercaptopurine, or methotrexate) can maintain remission. Antidiarrheal Agents Diarrhea can be controlled by loperamide (Imodium® ) 4 to 16 milligrams per day, diphenoxylate (Lomotil ® ) 5 to 20 milligrams per day, and in some cases, cholestyramine (Questran ® ) 4 grams one to six times a day. The mechanism of action of cholestyr amine is binding bile acids and eliminating their known cathartic action.  DISEASE COMPLICATIONS More than three out of four patients with Crohn’s disease will require surgery within the first 20 years of the onset of initial symptoms. Abscess and fissure formation is common. Abscesses can be characterized as intraperitoneal, visceral, retroperitoneal, interloop, or intramesenteric.

action.  DISEASE COMPLICATIONS More than three out of four patients with Crohn’s disease will require surgery within the first 20 years of the onset of initial symptoms. Abscess and fissure formation is common. Abscesses can be characterized as intraperitoneal, visceral, retroperitoneal, interloop, or intramesenteric. Signs and symptoms are worsening abdominal pain and tenderness, TABLE 73-5 Treatment of Fulminant Colitis Restore fluid and electrolyte balance Nothing by mouth Nasogastric suction for •  Obstruction •  Adynamic  ileus •  Suspected  toxic megacolon Parenteral corticosteroids •   Hydrocortisone 300 milligrams per day or methylprednisolone 48 milligrams per day or prednisolone 60 milligrams per day Broad-spectrum antibiotics •   Piperacillin-tazobactam 4.5 grams IV four times a day OR •   Ampicillin 2 grams IV four times a day + metronidazole 500 milligrams IV three times a day + ciprofloxacin (Cipro® ) 750 milligrams IV once a day Observe for complications •   Obstruction •   Perforation •   Toxic megacolon •   Life-threatening hemorrhage •   Intra-abdominal abscess Outpatient management (nontoxic patients) •   Liquids only for first 48 h Oral antibiotics •   Ampicillin, trimethoprim-sulfamethoxazole, ciprofloxacin, cephalexin, or rifaximin AND •   Metronidazole or clindamycin Tintinalli_Sec09_p0473-0562.indd 490 8/2/19 6:49 PM

fe-threatening hemorrhage •   Intra-abdominal abscess Outpatient management (nontoxic patients) •   Liquids only for first 48 h Oral antibiotics •   Ampicillin, trimethoprim-sulfamethoxazole, ciprofloxacin, cephalexin, or rifaximin AND •   Metronidazole or clindamycin Tintinalli_Sec09_p0473-0562.indd 490 8/2/19 6:49 PM CHAPTER 73: Disorders Presenting Primarily With Diarrhea 491 fever, and possibly a palpable mass. Retroperitoneal abscesses may cause hip or back pain and difficulty ambulating. Fistulas are the result of extension of the intestinal fissures seen in Crohn’s disease into adjacent structures. The most common sites are between the ileum and the sigmoid colon, the cecum, another ileal seg ment, urinary bladder, vagina, or the skin. Suspect an internal fistula when there are changes in the patient’s symptom complex, such as bowel movement frequency, amount of pain, or weight loss. Obstruction is the result of both stricture formation due to the inflammatory process and of edema of the bowel wall. It is the most common reason for emergent surgery in Crohn’s disease. The distal small bowel is the most common site of obstruction. Symptoms include crampy abdominal pain, distention, nausea, and bloating. Perianal complications include perianal or ischiorectal abscesses, fissures, fistulas, rectovaginal fistulas, and rectal prolapse. Perianal fistulas occur in 20% to 30% of Crohn’s patients. These are more commonly seen in patients with colonic involvement. Major GI bleeding is rare. Bleeding results from erosion into a vessel in the bowel wall. Toxic megacolon is also uncommon but is associated with massive GI bleeding in over half the cases. When bowel symptoms are present, malnutrition, malabsorption, hypocalcemia, and vitamin deficiency can be severe. In addition to the com plications of the disease are complications associated with the treatment of the disease with mesalamine, steroids, immunosuppressive agents, and antibiotics. These include leukopenia, thrombocytopenia, fever, infection, profuse diarrhea, pancreatitis, renal insufficiency, and liver toxicity. The incidence of malignant neoplasm of the GI tract is three times higher in patients with Crohn’s disease than for the general population, especially in patients with disease involvement of more than one third of their colon.  DISPOSITION Patients with colitis, peritonitis, or complications such as obstruction, significant GI hemorrhage, severe dehydration, or fluid/electrolyte imbalance should be hospitalized. Hospital admission should be con sidered in less severe cases that cannot be managed successfully with outpatient management. Surgical intervention is indicated in patients with complications of the disease, including intestinal obstruction or hemorrhage, perforation, abscess or fistula formation, toxic megacolon, and perianal disease. Before discharging patients with Crohn’s disease, discuss alterations in the therapeutic regimen with the gastroenterologist. Ensure close follow-up after discharge. ULCERATIVE COLITIS  INTRODUCTION AND EPIDEMIOLOGY Ulcerative colitis is a chronic inflammatory disease of the colon. The inflammation tends to be progressively more severe from the proximal to the distal colon. The rectum is involved nearly 100% of the time. The characteristic symptom is bloody diarrhea. The cause is unknown. The disease is more prevalent in the United States and northern Europe than in other parts of the world, and peak incidence occurs in the second and third decades of life. It is more common in men. First-degree relatives of patients with ulcerative colitis have a 15-fold risk of developing ulcerative colitis and a 3.5-fold risk of developing Crohn’s disease.  PATHOPHYSIOLOGY Ulcerative colitis involves primarily the mucosa and submucosa.

e occurs in the second and third decades of life. It is more common in men. First-degree relatives of patients with ulcerative colitis have a 15-fold risk of developing ulcerative colitis and a 3.5-fold risk of developing Crohn’s disease.  PATHOPHYSIOLOGY Ulcerative colitis involves primarily the mucosa and submucosa. Microscopically, the disease is characterized by mucosal inflammation with the formation of crypt abscesses, epithelial necrosis, and mucosal ulceration. The submucosa, muscular layer, and serosa are usually spared. In the usual case, the disease increases in severity more distally, with the rectosigmoid being involved in the vast majority of cases. In the early stages of the disease, the mucous membranes appear finely granular and friable. In more severe cases, the mucosa appears as a red, spongy surface dotted with small ulcerations oozing blood and purulent exudate. In very advanced disease, one sees large oozing ulcerations and pseudopolyps (areas of hyperplastic overgrowth surrounded by inflamed mucosa).  CLINICAL FEATURES The clinical features and course of ulcerative colitis vary and depend on the anatomic distribution of the disease in the colon. Crampy abdominal pain, bloody diarrhea, and tenesmus are typical symptoms. The disease is classified as mild, moderate, or severe depending on the clinical manifestations. Of all patients with ulcerative colitis, 60% have mild disease; in 80% of cases, the disease is limited to the rectum. Occasionally, con stipation and rectal bleeding are the presenting complaints. Progression to pancolitis occurs in 10% to 15% of patients with mild disease. Moderate disease is seen in 25% of patients. Patients demonstrate a good response to therapy. These patients usually have colitis extending to the splenic flexure (left-sided colitis) but may develop pancolitis. Patients with severe disease constitute 15% of those with ulcerative colitis and are most likely to be seen in the ED. Severe disease is associated with greater than six bowel movements per day, tachycardia, fever (>37.8°C), anemia (hemoglobin <10.5 milligrams/dL), an elevated erythrocyte sedimentation rate, low serum albumin, and more frequent extraintestinal manifestations. Patients with severe disease account for 90% of deaths from ulcerative colitis. Virtually all severely affected patients have pancolitis. Ulcerative colitis is usually characterized by intermittent attacks of acute disease with complete remission between attacks. Sometimes, the first attack is followed by a prolonged period of inactivity, or the disease is chronically active. The factors associated with an unfavorable prognosis and increased mortality include higher severity and extent of disease, a short interval between attacks, systemic symptoms, and onset of the disease after 60 years of age. Extraintestinal complications are listed in Table 73-4. Peripheral and axial arthritis and skin lesions including erythema nodosum and pyo derma gangrenosum are the most common extraintestinal complications.  DIAGNOSIS Laboratory findings in patients with ulcerative colitis are nonspecific and may include leukocytosis, anemia, thrombocytosis, decreased serum albumin, and abnormal liver function studies. There are many biomarkers, such as antineutrophil cytoplasmic antibodies, for diagnosis and prognosis, but none are available in the ED. These serologic markers also lack sensitivity. Therefore, the diagnosis of ulcerative colitis rests on the following: a history of abdominal cramps and diarrhea, mucoid stools, stool examination negative for ova and parasites, stool cultures negative for enteric pathogens, and confirmation of diagnosis by colonoscopy.

These serologic markers also lack sensitivity. Therefore, the diagnosis of ulcerative colitis rests on the following: a history of abdominal cramps and diarrhea, mucoid stools, stool examination negative for ova and parasites, stool cultures negative for enteric pathogens, and confirmation of diagnosis by colonoscopy. Differential Diagnosis The major diseases that should be considered in the differential diagnosis of ulcerative colitis include infectious colitis, Crohn’s colitis, ischemic colitis, radiation colitis, toxic colitis from antineoplastic agents, and C. difficile infection. When the disease is limited to the rectum, consider rectal syphilis, gonococcal proctitis, lympho granuloma venereum, and inflammations caused by herpes simplex virus, E. histolytica, Shigella, and Campylobacter.  TREATMENT Patients with severe ulcerative colitis should be treated with IV steroids, replacement of fluids, correction of electrolyte abnormalities, broad-spectrum antibiotics (ciprofloxacin, metronidazole, and ampicillin), mesa lamine, and steroids (Table 73-5). IV cyclosporine (4 milligrams/kg per day) or infliximab (5 to 10 milligrams/kg per dose) can be effective in fulminant colitis nonresponsive to IV corticosteroids. Triple-antibiotic therapy has been used for pediatric patients with severe ulcerative colitis. When toxic megacolon is suspected, place a nasogastric tube and obtain imaging and surgical consultation. The majority of those with mild and moderate disease can be treated as outpatients. In the treatment of patients with mild active proctitis, proctosigmoiditis, and left-sided colitis (<60 cm of active disease), topical treatment with mesalamine suppositories or enemas is effective. Topical glucocorticoid enemas or 5-aminosalicylic enemas (Rowasa ® , 2 to 4 grams/60 mL per day for 3 weeks) or suppositories (500 milligrams Tintinalli_Sec09_p0473-0562.indd 491 8/2/19 6:49 PM