Appendicitis, diverticulitis and colitis - Emerg Med Clin N Am, 2011

Appendicit is ,Diverticulit is , andColit is

Amanda E. Horn, MD*, Jacob W. Ufberg, MD

KEYWORDS

� Appendicitis � Diverticulitis � Colitis� Inflammatory bowel disease � Clostridium difficile� Emergency medicine

APPENDICITISOverview and Epidemiology

Appendicitis is the most common cause of abdominal pain requiring surgical interven-tion. The lifetime risk of appendicitis is approximately 7%, with a current incidence of86 per 100,000 patients per year.1 Rates of appendicitis are highest in the seconddecade of life, with a slightly higher incidence of appendicitis occurring in males (ratio1.4:1).2 Appendiceal perforation rates also vary; patients at extremes of age are morelikely to have perforated at their time of diagnosis.1 Early diagnosis of appendicitis isparamount, because patient morbidity is increased once appendicitis becomescomplicated by abscess and perforation.

Pathophysiology

The appendix is located on the posteromedial surface of the cecum, approximately3 cm from the ileocecal valve. Its length varies from 8 to 13 cm, and its anatomiclocationwithin the abdomen is variable.3 Although the appendix has no known function,recent studies propose that it acts as a reservoir for commensal bacteria in the colon.4

Appendicitis occurs when the appendiceal lumen becomes obstructed by fecaliths,adhesions, enlarged lymph nodes, foreign bodies, parasites, or, less commonly,tumors.5,6 Once obstruction occurs, the intraluminal pressure within the appendixbegins to increase as mucosal secretions accumulate, leading to appendiceal disten-sion. This distension in turn stimulates visceral afferent nerves that enter the spinalcord at the T8 to T10 level, causing dull epigastric or periumbilical pain. As obstructioncontinues, pressures within the appendix impede venous and lymphatic drainage,allowing bacteria and neutrophils to invade the walls of the appendix. More localized

Department of Emergency Medicine, Temple University School of Medicine, 10th Floor JonesHall, 3401 North Broad Street, Philadelphia, PA 19140, USA* Corresponding author.E-mail address: [email protected]

Emerg Med Clin N Am 29 (2011) 347–368doi:10.1016/j.emc.2011.01.002 emed.theclinics.com0733-8627/11/$ – see front matter � 2011 Elsevier Inc. All rights reserved.

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pain occurs after continued inflammation within the appendiceal serosa causes irrita-tion of local somatic fibers on the parietal peritoneum. If this process remainsunchecked, the appendix becomes gangrenous and is at risk for perforation, abscessformation, and peritonitis, often within 24 to 36 hours of symptom onset.7

Clinical Presentation

Classically, a patient with appendicitis presents with constant pain that is poorly local-ized to the periumbilical or epigastric region, and is accompanied by anorexia, nausea,and vomiting. Vomiting usually begins after the abdominal pain. Illness progressionleads tomigration of pain to the right lower quadrant at the area of theMcBurney point,and can be accompanied by low-grade fever. A meta-analysis evaluating patients withabdominal pain reported an increased likelihood of appendicitis when the patient’spain was located in the right lower quadrant, had migrated from the periumbilicalregion, and had been accompanied by fever.8

However, this classic clinical presentation is not always present, partly because ofthe variability of the appendiceal location within the abdomen. For example, theappendix may lie in a retrocecal, retroiliac, or pelvic location, leading to pain in the rightflank, pelvis, testicle, suprapubic region, or even left lower quadrant if the appendixcrosses the midline. Likewise, patients may experience dysuria, urinary frequency,diarrhea, or tenesmus depending on the location of the inflamed appendix. Thesevaried positions of the appendix and their associated complaints can delay the earlydiagnosis of appendicitis and increase the risk of gangrene and perforation.9

Multiple physical examination findings exist to aid in the diagnosis of appendicitis.Pain with palpation is classically found at the McBurney point, located “exactlybetween an inch and a half and two inches from the anterior spinous process of theileum on a straight line drawn from that process to the umbilicus.”10 A positive Rovsingsign is present when palpation of the left lower quadrant elicits tenderness in the rightlower quadrant. Patients may also show rebound tenderness or guarding, which areresponses to the inflamed parietal peritoneum, and, when present, have been foundto be independent predictors of appendicitis.11

Additional signs can aid in the physical diagnosis. The psoas sign is performedeither by having the patient flex at the right hip against resistance, or by extendingthe hip with the patient in the left lateral decubitus position, thereby irritating the iliop-soas muscle. A positive obturator sign is present when internal rotation of the flexedright hip with the knee in flexion exacerbates the patient’s pain. A rectal examinationis often performed, although the sensitivity and specificity of rectal tenderness forappendicitis are weak.8

Temperature is either normal or slightly increased early in the course of appendicitis.Patients may develop fever as the disease state progresses toward perforation andabscess formation. Therefore, temperature increase alone cannot rule in the diagnosisof appendicitis, but the presence of a fever, when taken in concert with other historyand physical examination findings, such as migration of pain, can make the diagnosismore likely.8

Special populationsPregnancy In theory, the gravid uterus can displace the inflamed appendix cephaladand lead to right upper quadrant or right flank discomfort. However, most pregnantwomen with appendicitis present with right lower quadrant pain, regardless of theirstage of pregnancy.12,13 There is a slightly higher incidence of appendicitis in thesecond trimester compared with the first and third.14 Although pregnant women arenot at increased risk for appendicitis compared with nongravid controls, appendicitis

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is the most common nonobstetric surgical emergency in pregnancy. Early recognitionin the pregnant patient with appendicitis is important because complications such asperitonitis or abscess formation can affect fetal outcomes. Studies have shown highrates of fetal loss in both uncomplicated and complicated appendicitis (15% and37%, respectively). Pregnant women are also at risk of early delivery, with some seriesshowing rates reaching 45%, although recent data show improvement in theseoutcomes.15,16

Children Young children and the aged are also at risk for delayed diagnosis of appen-dicitis and its complications, and therefore a high index of suspicion is necessarywhen evaluating these populations. Studies have found pediatric patients to be initiallymisdiagnosed with gastroenteritis, urinary tract infection, otitis media, or respiratoryinfections, ultimately increasing perforation rates (approximately 70%–80%) andhospital lengths of stay.17–19

Elderly Likewise, elderly patients tend to have a delay between symptom onset andtreatment of appendicitis. This delay leads to increased rates of perforation. Mortalityfrom appendicitis in the aged increases to 4% from 0.1% for younger patients, and isparticularly high in those greater than 70 years of age (32%). Reasons for delay in diag-nosing this population include misdiagnosis and atypical patient presentation,20,21

although more recent data show early computed tomography (CT) scanning and lapa-roscopy are improving outcomes.22

Immunocompromise Immunocompromised patients, such as those with acquiredimmune deficiency syndrome (AIDS), are also at risk for complications from appendi-citis, partly because of the similar symptoms that opportunistic infections can cause inthis population. Although patients with AIDS have been found to present with typicalsymptoms of appendicitis, these symptoms may be misattributed to opportunisticinfections or other AIDS complications. However, patients with AIDS are more likelythan those without the disease to be perforated at the time of surgical intervention.23

Recent retrospective data suggest that antiretroviral therapy may play a protectiverole in the development of appendicitis in patients with AIDS.24

Diagnosis

Appendicitis should be considered in the differential diagnosis for all patients present-ing with epigastric, periumbilical, or right-sided abdominal or flank pain. Although nosingle test is specific for appendicitis, some laboratory data may aid in the diagnosis.A urinary pregnancy test should be performed in all women of childbearing age, andpelvic examination should be performed in addition to the abdominal examination.Some women may have adnexal tenderness with inflamed pelvic appendices.A urinalysis should be performed as well, although it is important to keep in mindthat hematuria or pyuria can be present in appendicitis if the inflamed appendix is inclose proximity to the bladder or ureter.

LaboratoryThe clinical usefulness of a white blood cell (WBC) count with differential remainsuncertain. In one recent series, an increased WBC count of greater than 10,000cells/mm3 had a sensitivity of 76% and specificity of 52%.25 This is similar to otherdata showing that leukocytosis alone is a poor predictor of appendicitis and doesnot distinguish between simple versus complicated cases.26 The inflammatory markerC-reactive protein (CRP) has been shown to have both a low sensitivity and low spec-ificity when used alone in appendicitis evaluation.27,28 However, the combination of

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leukocytosis, leftward shift, and increased CRP may be more useful than each testalone in the diagnosis of appendicitis. A recent meta-analysis showed an increasedlikelihood of appendicitis when 2 or more of these studies were increased anda decreased likelihood when all 3 were within normal limits.29 Therefore, laboratorytesting should be seen as an adjunct to other elements of the history and physicalexamination when appendicitis is suspected, but cannot definitively make thediagnosis.

ImagingMultiple imaging studies in the evaluation of appendicitis exist, although the useful-ness of each study can vary. Plain films are seldom used in the diagnosis of appendi-citis; however, they can help rule out other causes of abdominal pain (volvulus,intussusception, or nephrolithiasis) and may be performed rapidly at the bedside.Signs suggestive of appendicitis on radiograph include localized paralytic ileus, gasor fecalith in the appendix, blurring in the area of the right psoas muscle, and freeair, although no sign is sensitive or specific in making the diagnosis,30 which limitsthe value of plain film in this disease.

UltrasoundUltrasound can be a useful test in the evaluation of appendicitis, particularly in childrenand pregnant women in whom there are particular concerns regarding ionizing radia-tion. The sensitivity of graded compression ultrasonography is as high as 98%(although these numbers vary widely between studies)31 and is considered positivefor appendicitis when the diameter of the appendix is greater than 6 to 7 mm(Fig. 1).27,32,33 Inflammation surrounding the appendix, appendicoliths, or hyperemiaof the appendiceal wall can also be visualized by ultrasound in the setting of acuteappendicitis. False negatives can occur once the appendix has perforated, thusreducing the diameter of the appendix, or when the appendix is retrocecal or inflam-mation is confined to the tip of the appendix.34 Another challenge in using ultrasoundis that the appendix cannot always be visualized. Even using skilled sonographers, theappendix is not visualized between 25% and 35% of the time,27,33 which can be partlycaused by patient’s body habitus or bowel gas overlying the appendix. The negativepredictive value of a nonvisualized appendix on ultrasound is 90%.27 Thus, althougha positive ultrasound is diagnostic of appendicitis, a negative ultrasound in whichthe appendix is not seen cannot rule out the diagnosis of acute appendicitis, and otherdiagnostic tools should be used.

CTCT has become widely used in the evaluation of suspected appendicitis. Advantagesinclude its widespread availability as well as its capacity to detect other abdominaldisorders. Disadvantages include patient radiation exposure, time delay to diagnosisif oral contrast is used, and risk of contrast-induced nephropathy or contrast reactionwhen intravenous contrast is used. Some investigators consider increased cost to bea disadvantage of this imaging modality, but data have suggested a decrease in therates of unnecessary appendectomy since CT scan use has increased.35 Findingssuggestive of acute appendicitis on CT scan include an enlarged appendix with diam-eter greater than 6 mm, appendiceal wall thickening, and pericecal inflammation(Fig. 2). An appendicolith alone is not sufficient to make a radiographic diagnosis ofappendicitis.36

Some controversy exists about the use of contrast in the evaluation of appendicitison CT. The sensitivity (83%–97%) and specificity (93%–98%) of CT in acute appendi-citis vary with the presence or absence of contrast, as well as type of contrast used.

Fig. 2. Appendicitis. ACTscan showsanedematous appendixwithadiametergreater than1 cm(arrow), consistentwith acute, uncomplicated appendicitis. (From Prather C. Inflammatory andanatomic diseases of the intestine, peritoneum, mesentery, and omentum. In: Goldman L,Ausiello DA, eds. Cecil medicine. 23rd edition. Philadelphia: Saunders, 2007; with permission.)

Fig. 1. Ultrasound shows an enlarged appendix with a fluid-filled lumen. (From Paterson A,Sweeney LE, Connoly B. Paediatric abdominal imaging. In: Grainger R, Allison D, eds.Grainger & Allison’s Diagnostic Radiology: A Textbook of Medical Imaging. 5th Edition.Philadelphia: Churchill Livingston, 2008; with permission.)

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A recent review article found the sensitivity and negative predictive value of CT withoutoral contrast to be equal to that of CT with oral contrast; the specificity, accuracy, andpositive predictive value of CT without oral contrast was superior to that of CT with oralcontrast in this analysis.37 The implication of this review may have important ramifica-tions on emergency department (ED) length of stay and may decrease time untilsurgical intervention for patients. Other studies have shown the sensitivity of noncon-trast scans to be greatly inferior to those using contrast.38

Another promising option uses rectal contrast only. In a series of 100 patients, CTwith rectal contrast had a sensitivity, specificity, positive and negative predictivevalues, and accuracy of 98% in diagnosing acute appendicitis.39 More recentprospective data have shown more modest outcomes for this modality, but implythat rectal contrast studies can be useful in the evaluation of acute appendicitis.38

Perhaps the best approach to the use of contrast in patients suspected of havingappendicitis should take into account the breadth of the differential diagnosis. Oraland intravenous contrast may help better delineate other causes of abdominal pain(particularly in young women) and should be considered when the diagnosis of appen-dicitis is uncertain. Establishing an institutional protocol with respect to contrastadministration may also aid in the decision of whether contrast should be used, andby what route.

Magnetic resonance imagingMagnetic resonance imaging (MRI) may also have a limited role in the work-up ofappendicitis. Unlike CT, MRI does not expose patients to ionizing radiation. It istherefore considered safe in pregnancy. Gadolinium crosses the placenta and shouldtherefore be avoided, particularly in the first trimester. Disadvantages include limitedavailability, high cost, and lengthy scan times. If obtainable, MRI may be a goodsecond-line imaging study when a pregnant patient has an indeterminate ultrasound.40

Clinical scoringSeveral scoring systems have been developed in an attempt to assist in the diagnosisof acute appendicitis. The most often cited is the MANTRELS score, which isa mnemonic that uses 8 different variables on a total 10-point scale.41 These variablesinclude migration of pain, anorexia, nausea or vomiting, tenderness in the right lowerquadrant, rebound tenderness, elevation of temperature, leukocytosis, and leftwardshift. The score may aid clinicians in deciding which patients can be observed andwhich require operative intervention. It has also been shown to be helpful in discrim-inating between patients who require imaging for suspected appendicitis and thosewho may be discharged without imaging.42

Treatment

Patients with appendicitis should receive intravenous hydration, symptomatic relief,and antibiotics. Electrolyte imbalances should be corrected and crystalloids adminis-tered for patients with dehydration or sepsis. Antiemetics should be considered inpatients with vomiting. Narcotic pain medication can be administered to maximizepatient comfort.A recent review article confirms that antibiotics can prevent postoperative

wound infection in uncomplicated appendicitis and minimize abscess formationin cases of perforation.43 Antibiotic therapy should include coverage for entericgram-negative organisms as well as anaerobes, and should be considered inconjunction with the consulting surgeon. Possible regimens include a second-generation or third-generation cephalosporin for uncomplicated cases. In the eventof abscess formation or perforation, broader-spectrum coverage with a medication

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such as piperacillin-tazobactam or a 3-drug regimen including a cephalosporin andaminoglycoside along with metronidazole is warranted.44

A study investigating antibiotic and medical management versus appendectomyshowed that, although most patients improved in the short term with medical manage-ment, greater than one-third of patients required surgery for recurrent appendicitiswithin a year.45 Therefore, operative intervention remains the definitive treatment ofacute appendicitis, and early surgical consultation is necessary. In cases of abscessformation at time of presentation, surgeons may opt for initial percutaneous abscessdrainage initially, followed by interval appendectomy.

DIVERTICULITISOverview and Epidemiology

Diverticular disease is commonly seen in the adult population. The overall prevalenceof diverticulosis has been reported to be roughly 27% and increases with advancingage.46 Of those patients with symptoms from diverticular disease, 3% are less than40 years of age, whereas each decade between the ages of 50 and 70 years accountsfor approximately 25% to 30% of cases.47 The prevalence is much higher in devel-oped countries, and is believed to be partly the result of physical inactivity48 anda low-fiber diet.49 Symptomatic disease, including diverticular pain and diverticulitis,occurs in roughly 10% to 25% of patients with diverticulosis.50

Pathophysiology

Diverticula are small outpouchings or herniations that form at areas of weakness in thewall of the colon. In general, they are located at the vulnerable areas in which the vasarecta enters the muscularis. Except for diverticula of the cecum, which comprise all3 layers of the colonic wall, most acquired diverticula contain mucosa and submucosaonly. Diverticular disease affects the left-sided and sigmoid colon more than 90% ofthe time.51 Although many causes of diverticulosis have been proposed, the exactcause of the condition is not known. Problems of colonic motility and muscular abnor-malities of the colon wall are possible causes. Another hypothesis is that diverticulosisis a disorder arising from increased intraluminal pressure.52 Although diverticulosis islargely an asymptomatic condition, these areas can perforate and become inflamed,leading to diverticulitis.Patients can have either complicated or uncomplicated episodes of diverticulitis,

which has ramifications for treatment as well as patient morbidity. Complicated casesare those in which there is perforation, obstruction, abscess, or fistula formation.53

Clinical Presentation

Patients with diverticulitis typically present with constant left lower quadrant or supra-pubic pain. Patients may also complain of fever, malaise, constipation, diarrhea,tenesmus, and urinary symptoms if the bladder becomes irritated by the inflamedcolon. On examination, patients typically have left lower-quadrant tenderness, whichmay be accompanied by localized guarding or rebound. At times, a palpable abdom-inal mass caused by an underlying abscess may be appreciated.Patients with acute diverticulitis may also present with right-sided abdominal symp-

toms. This possibility applies particularly to Asian54 and younger55 patients, who aremore likely to have proximal colonic disease. In addition, redundant sigmoid colonmay be present on the right side of the abdomen, leading to right-sided symptomsin patients with distal colonic disease.A high index of suspicion is necessary when evaluating patients who are elderly or

immunocompromised. These groups may present with less-impressive symptoms

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and physical examination findings. As a result, they are more likely to have perforationat the time of diagnosis.56,57

Patients may also complain of symptoms related to fistula formation, which mayoccur between the bowel and bladder, leading to pneumaturia or fecaluria, or betweenthe bowel and vagina, with women complaining of a feculent vaginal discharge. Inaddition, enterocolonic fistulas may occur and lead to copious diarrhea.

Diagnosis

Patients with acute diverticulitis often have an increased WBC count and may alsohave a leftward shift. Other laboratory abnormalities may be present in patients withvomiting and diarrhea or in those with more advanced septicemia.Imaging options are available when the diagnosis of diverticulitis is uncertain, or if

suspicion exists for complications of diverticular disease. Contrast enema hastypically been considered the gold standard in diagnosis, although it is falling out offavor as a first-line study. Although contrast enema is able to diagnose diverticulitis,it is unable to assess for the presence of an abscess and cannot determine the severityof inflammation.58 Thickened colonic folds, contrast extravasation, and localized masseffect may be seen on contrast radiography.59 Fistula formation may also be evident.The use of non–water-soluble contrast material in colonic contrast studies can alsolead to problems associated with intraperitoneal barium when perforation is present,and should therefore be avoided in patients with signs of local peritonitis on examina-tion. If this type of imaging is used, it is best to use water-soluble contrast.CT is the study most used for the diagnosis of diverticulitis. CT with both oral and

intravenous contrast has the advantage of being able to evaluate the colonic wallsas well as extraluminal areas, in addition to being able to assess for other causes ofabdominal pain. The sensitivity of CT for diagnosis of diverticulitis ranges from 85%to 97%.60 Positive findings of diverticulitis include thickening of the bowel wall andfascia, pericolic fat stranding, and local abscess formation (Fig. 3).61

Ultrasound also has a role in the radiologic evaluation of diverticulitis. Findingscompatible with the disease include a thickened colon wall with protrusions consistentwith diverticula. Pericolic inflammation may also be evident. Although the sensitivity ofultrasound in diverticulitis is modest (91%), its specificity was almost 100% in a studyevaluating patients with right-sided abdominal pain.62 As with the use of ultrasound forother diseases, its accuracy is highly operator dependent.

Fig. 3. CT scan of a patient with acute diverticulitis showing colon wall thickening, a massadjacent to the sigmoid, and stranding of the fat. (From Brandt LJ, Feuerstat P. Intestinalischemia. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger & Fordtran’s gastrointes-tinal and liver disease. 8th edition. Philadelphia: Saunders, 2010; with permission.)

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Treatment

The treatment of diverticulitis is largely dependent on the severity of illness and overallhealth status of the patient. Young immunocompetent patients with uncomplicateddiverticulitis may be managed as outpatients with oral antibiotics. Regimens shouldcover both gram-negative aerobes and anaerobes, and include a combination ofciprofloxacin and metronidazole, trimethoprim-sulfamethoxazole and metronidazole,or amoxicillin-clavulanic acid alone. Patients should be instructed to follow a liquiddiet with advancement to solids as tolerated after 2 to 3 days. These patients shouldreceive prompt follow-up to assess for response to treatment, and may require hospi-talization if symptoms do not improve. Surgical referral should be given to thosepatients experiencing a recurrence of diverticulitis. In addition, it is generally recom-mended that patients presenting with a first episode of diverticulitis undergo a colono-scopy about 6 weeks after the resolution of symptoms to evaluate for neoplasm andother diseases of the colon.Patients who have failed outpatient treatment, who require intravenous analgesia,

the elderly or immunocompromised, and those with complications of diverticulitisshould be hospitalized. Antibiotic options include intravenous ciprofloxacin andmetronidazole, or single-drug regimens of b-lactamase inhibitor combinations suchas ampicillin-sulbactam or ticarcillin-clavulanate. Severe infections may necessitatethe use of imipenem alone or the use of gentamicin or ciprofloxacin in combinationwith ampicillin and metronidazole. These patients warrant urgent surgical evaluationto determine the need for CT-guided percutaneous drainage or surgical resection.63

In general, between 15% and 30% of patients presenting with acute diverticulitisrequire operative intervention. An equal number have recurrences of their disease.64,65

COLITISInflammatory Bowel Disease

Overview and epidemiologyThe term inflammatory bowel disease (IBD) refers to 2 types of chronic intestinal disor-ders, Crohn disease (CD) and ulcerative colitis (UC). These diseases differ in theirpathophysiology, but are similar in their clinical presentation. Both diseases are char-acterized by a relapsing and remitting course of alimentary tract inflammation, andboth diseases require intensive chronic medical management during both exacerba-tions and periods of remission.IBD has a peak onset between 15 and 30 years of age, with a second small peak

later in life that is more consistently seen with UC than with CD.66 IBD affects morethan 1 million Americans, with CD and UC represented roughly equally. Worldwide,IBD prevalence varies with geographic location, with higher rates occurring in moreindustrialized countries and lower rates occurring in Asia, Africa, and South America.IBD is more common among the Jewish population, and studies have shown higherrates in white people than African Americans and Asians.67

PathophysiologyAlthough the exact cause of IBD remains unknown, a complex interplay of multiplefactors likely contributes to the development of these diseases. At present, the bestevidence points to an inflammatory response to intestinal microbes occurring ina host who is genetically susceptible to IBD.68 Numerous environmental factorshave also been shown to affect IBD. Cigarette smoking lowers the risk of UC forcurrent smokers, but the risk for those who stop smoking is higher than for thosewho never smoked.69 Conversely, smoking doubles the risk of Crohn disease.70

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Diet, oral contraceptives, and nonsteroidal antiinflammatory agents have also beenshown to influence IBD.71

The role of genetics in IBD is supported by twin studies that show a definite geneticpredisposition that is stronger in CD than in UC.72 It is thought that microbes also playa role, with inflammation believed to be the result of a dysfunctional response to infec-tion. However, no particular bacterium has been identified in studies as the pathogeniccause of IBD.71 The immune system clearly plays a significant role in IBD, and manyagents used for the treatment of disease are immunosuppressive or specifically targetcertain aspects of immune system dysregulation.73

Crohn disease is characterized by involvement of any part of the gastrointestinaltract, but most frequently involves the distal small intestine and colon. The inflamma-tion is transmural, sometimes leading to the development of fistulas, abscesses, orstrictures. Themucosa often assumes a cobblestone appearance, and granulomatousdisease is commonly present. The lesions may be discontinuous (skip lesions), whichmay help to distinguish between forms of IBD. Perianal involvement, with fistula forma-tion and perianal abscess formation, is common in CD.UC leads to inflammation of the mucosa and submucosa of the colon. Transmural

involvement is rare, leading to little, if any, perianal disease or fistula formation. UCgenerally appears as a continuous lesion confined to the colon, and the absence ofskip lesions can help distinguish this disease from CD. Rectal involvement is the rule,with inflammation extending a variable distance into the colon. The inflammation ofUC often takes the appearance of ulceration, and cobblestoning of the mucosa is rare.

Clinical presentationPatients with IBD typically present with diarrhea and varying amounts of crampyabdominal pain. Diarrhea in UC may be bloody and is typically frequent and small involume. Tenesmus or fecal incontinence may also occur. These diarrheal featuresare also typical of CD with colonic involvement. However, in CD limited to the smallintestine, stools may be less frequent and larger in volume, and tenesmus is absent.Vomiting may be present, and, if significant, should lead to the consideration of bowelobstruction.Abdominal pain and tenderness in IBD are variable based on the anatomic location

of disease. Tenderness may be isolated to the rectum or the left lower quadrant, as isoften the case in UC. In other cases, it may be localized to the right lower quadrant,such as in patients with ileal CD. Pain and tenderness may be diffuse in patientswith significant areas of bowel involvement. Thickened bowel loops or an abscessmay lead to a palpable mass and tenderness at the affected location. Patients maypresent with frank peritonitis if bowel perforation has occurred.Patients with CD are prone to fistula and abscess formation because of the trans-

mural nature of disease. The location of fistula and abscess formation correlateswith the location of disease. Patients with isolated small intestine involvement aremore prone to internal fistula formation, whereas perianal disease presents morecommonly in patients with ileocolic disease.74

Patients with IBD may present with systemic complaints, such as fever, fatigue, andweight loss. Often, symptoms are gradually progressive and, more frequently in CD,may be intermittently present for a long period of time before diagnosis. Some degreeof dehydration and malnutrition may also be present.Inmost cases, the severity of IBD flares canbeclassifiedasmild,moderate, or severe.

Mild flares are classified as having no systemic toxicity, fewer than 4 bowel movementsper day with little or no blood, and an erythrocyte sedimentation rate (ESR) of less than20 mm/h. Severe flares are classified as having systemic toxicity, 6 or more bowel

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movements per day with blood, and ESR greater than 30 mm/h. Moderate flares havesymptoms that are between the criteria for mild and severe.75 Some patients maypresent with serious complications of IBD (see Serious Complications of IBD).

DiagnosisMany patients present to the ED with a known diagnosis of IBD. It has previously beenshown that compliance with maintenance therapy reduces the risk of acute attacks,76

and thus patients should be queried as to medication compliance.No specific testing routinely available in the ED can reliably diagnose IBD, and

endoscopy with biopsy is generally necessary to confirm the diagnosis. Patients pre-senting with IBD may be anemic because of chronic disease or bloody stools. Electro-lyte abnormalities may occur because of significant diarrhea or vomiting or because ofmalabsorption. Nonspecific markers of inflammation, such as the ESR or CRP, arefrequently increased.Plain radiography may be useful in cases in which bowel obstruction, perforation, or

toxic megacolon (see Serious Complications of IBD) are suspected. However, in mostIBD cases presenting to the ED, plain radiography is unlikely to be of benefit. CT maybe helpful to identify extraluminal complications such as nephrolithiasis, abscess,obstruction, or perforation, but severity of disease does not otherwise correlate wellwith radiographic findings.

TreatmentMedical therapy in the treatment of IBD is centered on supportive care as well asa variety of antiinflammatory and immunosuppressive agents. In patients with knownIBD, treatment should be decided in concert with the patient’s physician, because IBDmanagement is a chronic, ongoing process tailored on a patient-by-patient basis.Medications commonly used to treat IBD are discussed later. An ED approach totreatment of IBD follows this description.

Supportive care Dehydration and electrolyte imbalance should be treated with intra-venous fluids and electrolyte supplementation as needed. Anemia caused by serioushemorrhage should be addressed with blood transfusion if necessary. Pain medica-tions should be used as needed, but opiates are discouraged as part of the chronicmanagement of IBD. Nonsteroidal antiinflammatory medications may exacerbateIBD and should be avoided. Antidiarrheal agents may be useful in mild IBD to decreasethe number of stools and improve rectal urgency, but they should be avoided in severedisease because of the risk of precipitating toxic megacolon.

Aminosalicylates These agents are the cornerstone of therapy for UC, and althoughthey are less effective in CD, they are also often used as maintenance therapy forpatients with CD. The choice of preparation and route of these 5-aminosalicylic acid(5-ASA) derivatives is based on the location of disease. Suppositories are often usefulin patients with rectal disease, and retention enemas treat the rectum and descendingcolon. For patients with diffuse disease, oral controlled-release formulations are mostsuccessful, sometimes in combination with suppositories or enemas.

Corticosteroids Corticosteroids are often used as first-line agents in CD, and are usedin UC which is refractory to 5-ASA preparations. Oral steroids are effective in themanagement of mild-to-moderate exacerbations of disease, with parenteral steroidsreserved for more severe disease requiring hospital admission. The typical dose ofprednisone used is 40mg/d, and therapy can be slowly tapered once symptoms beginto diminish. The many known adverse effects of long-term corticosteroid use limit therole of steroids in maintenance therapy.

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Immunomodulators Azathioprine and mercaptopurine (6-MP) are immunomodulatorsthat have been shown to be effective in CD and, to a lesser degree, in UC. These drugsare useful in patients who are refractory to corticosteroids, or to help reduce cortico-steroid dependence in those who are unsuccessful in weaning from steroids.

Antibiotics Antibiotics have a limited role in UC, but have shown some usefulness inCD and in infectious complications of CD such as perianal fistula and abscess. Metro-nidazole and ciprofloxacin are the 2 most commonly used agents.

Anti–TNF-a antibody Infliximab is effective in managing moderate-to-severe Crohndisease, as well as in healing fistula disease associated with CD.77 A recent Cochranereview also showed usefulness in patients with difficult-to-treat UC.78

Initial ED treatment of IBD Supportive therapy should be instituted as indicated for allpatients. If possible, the patient’s treating physician should be contacted to ensureappropriate therapy based on the type of IBD, location of disease, and previousresponse to therapy.In general, first-line therapy for patients with mild-to-moderate UC should be with

oral 5-ASA derivatives, whereas enemas or foams are appropriate for those with proc-titis only. For those with UC who are failing several weeks of 5-ASA agents, corticoste-roids are the next therapeutic step. Patients who are failing steroids may be steppedup to another therapy, but this should always be done at the discretion of the patient’sgastroenterologist.First-line therapy for mild-to-moderate CD usually involves oral corticosteroids or

antibiotics. If the patient has significant abdominal pain, fever, or increased leukocytecount, an abdominal CT should be strongly considered to rule out abscess or perfo-ration before instituting steroid therapy. To increase the likelihood of success ofsteroid withdrawal, 5-ASA preparations are often added, but they are not generallyconsidered first-line therapy for CD.Patients with severe IBD from either UC or CD should receive aggressive supportive

care. Parenteral corticosteroids are often necessary, but only after suppurativedisease has been ruled out (predominantly in CD). Care should be taken toensure that no serious complications of IBD are present (see Serious Complicationsof IBD). Other causes of colitis should be considered, including enteric infection (espe-cially Clostridium difficile infection), radiation colitis, and ischemic colitis. Appropriateconsultation with a gastroenterologist should occur as soon as possible, and thepatient should be admitted to the appropriate level of care based on clinicalpresentation.

Serious complications of IBDComplications associated with UC Acute fulminant colitis occurs when inflammationextends beyond the colonic mucosa. Patients present with overt signs of systemictoxicity in addition to abdominal pain and bloody diarrhea. Leukocytosis and meta-bolic acidosis are often present.79 Plain radiography may show an edematous colonwith thumbprinting. This condition may progress to toxic megacolon. These patientsrequire aggressive supportive care, and enteric infections should be ruled out withstool studies. Broad-spectrum antibiotics should be considered, especially if perfora-tion is suspected, and gastroenterologic and surgical consultation should occuremergently.Toxicmegacolon results as the bowel becomes paralyzed andbegins to dilate. Signs

of systemic toxicity are present, and the colon is generally more than 6 cm in diameter(Fig. 4). When the colon reaches 12 to 15 cm, perforation is likely imminent.79 Enteric

Fig. 4. Toxic megacolon. The ascending and transverse colon appears gas-filled and dilatedwitha thickenedwall. There is anabsenceofhaustralmarkings, indicating full-thicknessmuralinflammation. (FromMorrison I. Theplainabdominal radiographandassociatedanatomyandtechniques. In: Grainger R, Allison D, eds. Grainger & Allison’s Diagnostic Radiology: ATextbook of Medical Imaging. 5th Edition. Philadelphia: Churchill Livingston, 2008; withpermission.)

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infection should be ruled out, as in fulminant colitis. Gastrointestinal decompressionwith a nasogastric tube should occur, and aggressive resuscitation and supportivecare should be instituted. Although the initial management is often medical, surgicalconsultation is necessary to evaluate the need for urgent operative intervention.Lower gastrointestinal bleeding is common in IBD, although life-threatening

bleeding is uncommon. Aggressive supportive care should occur, as in other causesof lower gastrointestinal bleeding, and surgical treatment is often necessary.79

Complications associated with CD In patients with CD, intra-abdominal and perirectalabscesses are common. In CD, perforation often creates a walled-off abscess ratherthan acute peritonitis because of seepage of bacteria through sinus tracts.79 The signsand symptoms of acute CD exacerbation may be difficult to distinguish from an intra-abdominal abscess. CT scanning is often necessary to clarify the diagnosis. Manage-ment of intra-abdominal abscess includes broad-spectrum antibiotics and earlyconsultation for operative or percutaneous drainage.Perirectal abscess may be treated as in patients without CD. Antibiotics should be

initiated. The choice of metronidazole and ciprofloxacin is often used, because theymay also aid in fistula healing, although there is no strong evidence to support thiscommon practice.Bowel obstruction is a common problem in CD, with the most common location

being the terminal ileum. Most patients have repeated partial small bowel obstructionsrather than complete obstructions, and thus may respond to supportive managementwith bowel rest and nasogastric suction. Surgical consultation should be requested,but most patients improve without operative intervention.79

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Extraintestinal manifestationsExtraintestinal manifestations of IBD may occur simultaneously with flares of boweldisease, or may be temporally unrelated to the course of bowel disease. Commonextraintestinal manifestations include arthritides such as ankylosing spondylitis,hepatic manifestations including hepatitis, pericholangitis, sclerosing cholangitis(UC), and gallstones or renal stones (CD). Other complications may be dermal(pyoderma gangrenosum and erythema nodosum) or ocular (uveitis and episcleritis).For reasons that are unclear, thromboembolic disease is more common in patientswith IBD. Most of these thromboembolic events manifest as thrombophlebitis, lowerextremity deep venous thrombosis, or pulmonary embolus.80 Thromboembolismmay also affect the portal vein, leading to variceal bleeding. Many other sites of throm-boembolism can also occur, including cerebral vascular occlusions.

DispositionMost patients with mild-to-moderate IBD exacerbation may ultimately be dischargedto follow-up closely with their physician. Alterations in therapy should be discussedwhenever possible with the physician managing the patient’s disease. Patients withsevere disease, or ill-appearing patients who are failing outpatient steroid therapy,require hospitalization. In addition to hospital admission, patients with severe compli-cations of IBD also require emergent consultation with gastroenterology and surgery.

C difficile Colitis

Overview and epidemiologyC difficile is a highly transmissible, gram-positive, spore-forming anaerobic bacteriumthat colonizes about 3% of healthy adults and 16% to 35% of hospitalized patients.81

This organism is identified as the cause in 10% to 25% of cases of antibiotic-associated diarrhea, 50% to 75% of antibiotic-associated colitis, and more than90% of antibiotic-associated pseudomembranous colitis.81 The epidemiology ofC difficile is changing rapidly, with a recent large increase in disease frequency,severity, and rate of treatment failure.82 This has correlated with the emergence ofa new and highly virulent strain designated NAP1.Antibiotics are the most widely recognized risk factor, and almost all cases are asso-

ciatedwith prior use.81 Theantibioticsmost commonly associatedwithCdifficile includeclindamycin, fluoroquinolones, and the third-generation cephalosporins, although anyantibiotic may predispose patients to colonization. Increased duration of therapy, useof multiple agents, and broader-spectrum antibiotic use all increase the incidence,although even single perioperative doses of antibiotics have been implicated.83,84

Other established risk factors include hospitalization, advanced age, and severeunderlying illness. Acid suppression, gastrointestinal surgery, and chemotherapyhave also been implicated in C difficile–associated disease. The incidence ofcommunity-associated infection, although low, is rising, and infection may occur inthe absence of risk factors.85

PathophysiologyMost commonly, antibiotic exposure alters the gut flora, allowing C difficile tomultiply. C difficile releases 2 toxins that cause colitis and diarrhea, an enterotoxintermed toxin A and a cytotoxin termed toxin B. In addition, the NAP1 strain producesbinary toxin, which is not present in other strains. These toxins act through a varietyof mechanisms to cause neutrophil activation and chemotaxis, cell retraction,apoptosis, and disruption of intercellular tight junctions. This process leads to waterydiarrhea, colitis, and the formation of pseudomembranes. Severity of disease iscorrelated with stool toxin levels.86

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Clinical presentationThe clinical presentation of C difficile colitis is highly variable. Most patients reporta previous history of antibiotic exposure, and most of those either present duringthe course of antibiotics or within several weeks of completion. Symptoms may beginas late as months after antibiotic completion. Patients may present with diarrhea, mildcolitis, pseudomembranous colitis, fulminant colitis, or toxic megacolon.Patients with mild-to-moderate disease generally present with lower abdominal

cramping and nonbloody, watery diarrhea, but lack systemic symptoms. Patientswith more severe colitis present with profuse watery diarrhea that may have occultblood, crampy abdominal pain and bloating, and systemic signs and symptomssuch as dehydration and fever. Patients with fulminant colitis present with severeabdominal pain, fever, diarrhea, bloating, and appear clinically ill. Physical examina-tion findings are variable based on severity of disease, but may range from isolatedmild lower abdominal tenderness to severe tenderness, peritonitis, distention, fever,and signs of shock.

DiagnosisThe gold standard test for diagnosis is the cell cytotoxicity assay. It is a sensitive assaybut is labor intensive, not widely available, and results are slow to return. In clinicalpractice, most institutions are using commercially available enzyme immunoassay(EIA) kits. These tests are easy to use, can be batched, and results are available withinhours. EIA kits may test for toxin A alone or for both toxins A and B, but testing for bothtoxins is preferred. EIA testing is less sensitive than the cytotoxicity assay; however,the yield may be increased by as much as 10% if serial testing is performed.87

Other laboratory testing may be suggestive, but not diagnostic. Fecal leukocytesare usually present and may help to distinguish between mild C difficile and otherantibiotic-associated diarrhea. Patients with more severe disease often have a leuko-cytosis, which may be profound in patients with fulminant colitis. Sigmoidoscopy mayalso help make the diagnosis if classic pseudomembranes are visualized. When thedisease is particularly severe, thickening of the wall of the colon may be seen on CTscan, but it is not diagnostic of C difficile. Plain radiography is not widely useful, butshould be obtained if toxic megacolon or perforation is suspected.

TreatmentWhenever possible, the offending antibiotic should be stopped or, if this is notpossible, switched to an agent less commonly associated with C difficile infection.Supportive management with fluid and electrolyte repletion should be given as indi-cated, and contact precautions should be instituted if infection is proved or sus-pected. Patients with typical symptoms and a positive EIA should receiveantibiotics, and treatment may be started pending EIA results if clinical suspicionis high.Antibiotic treatment of mild-to-moderate disease is generally with oral metronida-

zole or oral vancomycin. Most recommendations favor metronidazole as first-linetherapy because of lower cost and similar efficacy. The recommended regimen is500 mg 3 times daily or 250 mg 4 times daily for 14 days. If oral vancomycin isused, the dosage is 125 mg 4 times daily for 14 days. Intravenous metronidazolemay be used if oral therapy cannot be given, but intravenous vancomycin has no clin-ical effect on C difficile colitis.Relapse occurs in roughly 14% of patients after treatment.88 Relapse does not

necessarily indicate metronidazole resistance, and most patients respond to anothercourse of metronidazole. The addition of the probiotic Saccharomyces boulardii to oral

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antibiotics has been shown to decrease the number of recurrences in patients withrelapse, but it did not prove beneficial in the first episode of disease.89

Patients with severe C difficile disease require antibiotic therapy, aggressivesupportive care, and close monitoring. The possibility of toxic megacolon should beconsidered. Oral vancomycin (at 500 mg 4 times daily) is preferred for severe cases,and showed a significantly higher cure rate in a head-to-head study withmetronidazole.90 Patients with ileus may benefit from the addition of intravenousmetronidazole. Some severely ill patients may require surgery for toxic megacolon,perforation, necrotizing colitis, or severe disease with systemic toxicity refractory totreatment. Surgical consultation should be considered in the severely ill patient withC difficile–associated disease.

DispositionMost patients with mild symptoms caused byC difficile infection may be discharged tohome, with close follow-up with their primary care provider. If EIA results are not avail-able at the time of discharge, appropriate follow-up of test results with appropriatetreatment must be ensured. Patients with severe disease require admission to theappropriate level of inpatient care.

Ischemic Colitis

Overview and epidemiologyIntestinal ischemia is rare. However, ischemic colitis is the most frequent type ofmesenteric ischemia, and predominantly affects the elderly.91 Most patients have non-gangrenous ischemia, which is generally transient and resolves without long-termcomplications. Ischemic colitis may present insidiously, and often no cause is identi-fied. In addition to age, several risk factors exist for colonic ischemia, including recentaortoiliac surgery, myocardial infarction or heart failure, extreme exercise (such asmarathon running or triathlon competitions), and prothrombotic conditions.

PathophysiologyThe colon has considerable collateral blood supply, which is weakest at the splenicflexure and the rectosigmoid junction. As such, these 2 areas are at greatest risk forischemia during systemic hypoperfusion events. Most episodes are secondary tosystemic low-flow states and rarely occur as a result of large artery disease. Colonicinjury from an ischemic event may be caused by either hypoxia or subsequent reper-fusion injury, or both.

Clinical presentationManifestations of colonic ischemia are variable based on the extent and duration ofthe ischemic event. Patients generally present with acute onset of mild, crampyabdominal pain, usually on the left side. Rectal bleeding or bloody diarrhea arecommon and develop within 24 hours of the onset of pain. Ischemic colitis differsfrom mesenteric ischemia of the small bowel in that the pain is generally less severeand often located laterally, rectal bleeding is usually an earlier finding, and patientsdo not typically appear severely ill.92 When more severe pain, peritonitis, fever, orsystemic toxicity is present, colonic infarction with gangrene or perforation shouldbe considered.

DiagnosisNo accurate laboratory markers exist to diagnose ischemic colitis. However, markersof hypoperfusion, such as the serum lactate and anion gap, may be increased in signif-icant disease. Lower endoscopy often clarifies the diagnosis but is rarely performed in

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the ED. Plain radiography may show signs of colonic dilation, but more specific signssuch as thumbprinting of the bowel wall because of submucosal edema or hemor-rhage were present in only 30% of patients with mesenteric infarction in one series.93

A CT scan with intravenous contrast is generally the first imaging test in patients pre-senting with suspected colonic ischemia. However, early scans may be normal, andfindings such as bowel wall thickening are nonspecific. Pneumatosis may be seenin advanced disease. Angiography is rarely diagnostic. Often, blood flow has normal-ized at the time of the study and ischemia is rarely caused by large vessel occlusion.

TreatmentIn cases of suspected nonocclusive ischemia, aggressive supportive care is the main-stay of therapy. Patients should receive intravenous fluids to improve perfusion, andcardiac status and oxygenation should be maximized. Bowel rest should be imple-mented, and nasogastric suctionmay be necessary if an ileus is present. Careful moni-toring should be instituted to detect signs of clinical deterioration early.In cases of suspected or documented infarction, aggressive supportive care is

necessary, and broad-spectrum antibiotics should be initiated. A surgeon should beconsulted for likely operative intervention, because bowel necrosis can lead to perfo-ration, peritonitis, and sepsis.

DispositionPatients with mild symptoms from a detectable, reversible cause such as extremeexercise may be managed on an outpatient basis if symptoms improve with treatmentin the ED. However, the diagnosis of colonic ischemia is rarely confirmed in the ED,and disposition is generally based on the presenting clinical picture. Most patientsdo not ultimately require surgery, but all ill-appearing patients with suspected colonicischemia should be hospitalized.

Radiation Proctocolitis

The gastrointestinal epithelium has a high cell turnover rate, making it susceptible tofree radical injury from radiation therapy. As such, sloughed endothelium is notreplaced at the normal rate, leading to ulcerations, edema, and inflammatory changes.Radiation proctocolitis can manifest either early (during or soon after completion ofa course of radiation therapy), or late (usually months to years after therapy).Acute radiation proctocolitis presents with abdominal pain, diarrhea, malaise, and

bleeding. Tenesmus may be present if the rectum is involved. The diagnosis ismade clinically based on the history of radiation therapy and the symptoms involved.Treatment is symptomatic, and should be decided in conjunction with the physicianperforming the radiation therapy.Chronic radiation proctocolitis may present with a variety of symptoms. In patients

with ulcerative disease, these include pain, bleeding, and tenesmus. In cases of stric-ture formation, patients may present with constipation, decreased stool caliber, orsigns of partial or complete obstruction. Patients may also present with fistula diseaseor signs of pancolitis. Some patients with fistula disease or stricture ultimately requiresurgery, but this is often not performed emergently. Treatment of chronic radiationproctocolitis is symptomatic and based on the presenting clinical picture.

SUMMARY

Appendicitis, diverticulitis, and colitis are diseases that commonly present to the ED.Acute appendicitis may present classically, but often the diagnosis is difficult becauseof variablesymptomsandexamination findings,aswell as the lackofaperfect laboratory

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or imaging test. Diverticulitis usually presents with left-sided abdominal symptoms, butright-sided disease occurs in aminority of patients and should be considered in youngerpatients and those of Asian descent. Colitis may be caused by IBD, infection, ischemia,or radiation therapy. The treatment of colitis varies based on its cause.

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