You are in: eMedicine Specialties > Radiology > GASTROINTESTINAL Ulcerative ColitisArticle Last Updated: Apr 26, 2007AUTHOR AND EDITOR INFORMATIONAuthor: Ali Nawaz Khan, MBBS, LRCP, FRCS, FRCP, FRCR, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia Ali Nawaz Khan is a member of the following medical societies: American Institute of Ultrasound in Medicine, Radiological Society of North America, Royal College of Physicians, Royal College of Physicians and Surgeons of the USA, Royal College of Radiologists, and Royal College of Surgeons of England Coauthor(s): Aali J Sheen, MBChB, FRCS, Specialist Registrar, Department of HPB Surgery, Manchester Royal Infirmary Oxford Road Manchester UK; Sumaira Macdonald, MBChB, MRCP, FRCR, PhD, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute; Haren Varia, MB ChB, FRCR, Consultant, Department of Clinical Radiology, Blackpool, Fylde and Wyre NHS Trust Editors: Jocelyn D Chertoff, MD, Associate Professor of Radiology and Obstetrics/Gynecology, Dartmouth Medical School; Consulting Staff, Department of Diagnostic Radiology, Dartmouth-Hitchcock Medical Center; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; David Andrew Nicholson, BM, BS, FRCR, Honorary Lecturer, Department of Radiology, University of Manchester; Consultant Gastrointestinal Radiologist, Department of Radiology, Hope Hospital, Salford Royal Hospital NHS Trust; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center Author and Editor Disclosure Synonyms and related keywords: UC, inflammatory bowel disease, IBD, ulcerative proctocolitis, crypt abscesses, fulminant colitis, toxic megacolon, Crohn disease, Crohn's disease, CD INTRODUCTIONBackgroundUlcerative colitis is a type of inflammatory bowel disease (IBD) that characteristically involves the large bowel. It is recognized as a multifactorial polygenic disease, as the exact etiology is still unknown. Included in the etiologic theories are environmental factors, immune dysfunction, and a likely genetic predisposition. Some have suggested that children with a below-average birth weight who are born to mothers with ulcerative colitis have a greater risk of developing the disease. Histocompatibility human leukocyte antigen (HLA)–B27 is identified in most patients with ulcerative colitis, though this finding is not associated with the condition. Immune dysfunction has been postulated as a cause, with limited clear evidence. Ulcerative colitis might also be linked to diet, though diet is thought to play a secondary role. Food or bacterial antigens might exert an effect on the already damaged mucosal lining, which has increased permeability. For excellent patient education resources, visit eMedicine's Crohn Disease Center and Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles Inflammatory Bowel Disease, Crohn Disease, and Crohn Disease FAQs. PathophysiologyUlcerative colitis involves only the mucosa, with the formation of crypt abscesses and a coexisting depletion of goblet cell mucin. In severe cases, the submucosa can be involved, and in some cases, the deeper muscular layers of the colonic wall can also be affected. Acute severe colitis can result in a fulminant colitis or toxic megacolon, which is characterized by a thin-walled, large, dilated colon that can eventually become perforated. Chronic disease is identified with pseudopolyp formation in about 15-20% of cases. Chronic and severe cases can exhibit areas of precancerous changes, such as carcinoma in situ or dysplasia. Anatomically, the large majority of cases arise in the rectum, with some patients developing terminal ileitis due to an incompetent ileocecal valve. In these cases, about 30 cm of the terminal ileum is usually affected. Various immunologic changes have been documented:
The bowel wall is thin or of normal thickness, but the presence of edema, the accumulation of fat, and hypertrophy of the muscle layer may give the impression of a thickened bowel wall. The disease is largely confined to the mucosa and, to a lesser extent, the submucosa. Muscle-layer and serosal involvement is rare and seen in those with severe disease, particularly toxic dilatation. Early disease manifests as hemorrhagic inflammation with loss of the normal vascular pattern, as petechial hemorrhages, and as bleeding. Edema is present, and large areas become denuded of mucosa. Undermining of the mucosa leads to the formation of crypt abscesses, which are the hallmark of the disease. Microscopic changes include inflammation of the crypts of Lieberkuhn and abscesses. These findings are accompanied by a discharge of mucus from the goblet cells, which become reduced in number as the disease progresses. The ulcerated areas are soon covered by granulation tissue. Excessive fibrosis is not a feature of the disease. The undermining of mucosa and the excesses of granulation tissue form polypoidal mucosal excrescences, which are known as inflammatory polyps or pseudopolyps. FrequencyUnited StatesIn the Western world, ulcerative colitis has a prevalence of 3-10 cases per 100,000 population. Ulcerative colitis is 3 times more common than Crohn disease. InternationalGeographically, ulcerative colitis is more common in the Western and Northern hemispheres and has a low incidence in Asia and the Far East. Mortality/MorbidityUlcerative colitis can result in disease-related mortality. However, overall mortality is not increased in patients with ulcerative colitis as compared with the general population. An increased mortality may be observed in the elderly population with the disease. Patients who develop complications (eg, shock, malnutrition, anemia) may also have an increased mortality. Evidence suggests that patients with ulcerative colitis who undergo any form of medical or surgical intervention have an increased mortality rate.
RaceUlcerative colitis is more common in individuals living in temperate climates and in the Caucasian population, with sporadic increases in some Jewish populations. The disease is uncommon in the Far East. SexUlcerative colitis is slightly more common in men than women. AgeUlcerative colitis is uncommon in persons younger than 10 years. Most patients are aged 20-40 years at diagnosis. Another peak occurs at age 60 years. AnatomyUlcerative colitis predominantly affects the colon and, occasionally, the terminal ileum. The anatomic distribution can be grouped as colonic or extracolonic manifestations. As a rule, ulcerative colitis involves the rectum, even when the rest of the colon is spared. In some patients with pancolitis, the terminal ileum displays a superficial mucosal inflammation called backwash ileitis. Carcinoma is a known complication of ulcerative colitis in the small group of patients who have had the disease for approximately 10 years. The cancer tends to be multicentric, atypical in its appearance, and rapidly metastasizing. Clinical DetailsPatients with ulcerative colitis predominantly complain of increasing fresh bleeding per rectum, with frequent stools and mucus discharge per rectum. In severe cases, purulent rectal discharge can result with lower abdominal pain and severe dehydration, especially in the elderly population. Some patients also describe tenesmus. Findings from abdominal examination are usually unremarkable. The diagnosis is best made at endoscopy, which highlights an abnormal erythematous mucosa with or without ulceration. Contact bleeding may also be observed, with mucus identified in the lumen of the bowel. Biopsy of the mucosa is recommended to identify the extent of the disease with respect to the thickness of the bowel wall. Barium enema study can also be performed to identify a tubular colon. Routine blood tests to be performed include assays for C-reactive protein and serum albumin. In toxic megacolon, perforation is always a risk; this renders the patients acutely unwell. The severity of ulcerative colitis can be graded as follows:
Preferred ExaminationPlain abdominal radiographs are a useful adjunct to imaging in acute onset ulcerative colitis. The images may show colonic dilatation in severe cases, suggesting toxic megacolon, evidence of perforation, obstruction, or ileus. Radiographic imaging studies have an important role in the workup of patients with suspected IBD and in the differentiation of ulcerative colitis and Crohn disease. Because of its ability to depict fine mucosal detail, double-contrast barium study is a valuable technique for diagnosing ulcerative colitis and Crohn disease, even in patients with early disease. Traditionally, barium enema examination has been the mainstay of radiologic investigation for suspected ulcerative colitis. Transabdominal ultrasonography (US) is a noninvasive study that can be helpful in the diagnosis of IBD, but it cannot be used to distinguish between ulcerative colitis and Crohn disease. US is also a useful technique in the investigation of biliary complications of the disease. Generally, CT has a limited role in the diagnosis of uncomplicated ulcerative colitis. However, CT scans play an important role in the differential diagnosis of ulcerative colitis and is an excellent modality in the diagnosis of complications associated with the disease. Biliary dilatation suggests primary sclerosing cholangitis. Cross-sectional imaging studies such as CT, MRI, and US are useful for showing the effects of these conditions on the wall of the bowel and for demonstrating intra-abdominal abscesses and other extraluminal findings in patients with more advanced disease. Thus, barium studies and cross-sectional imaging studies have complementary roles in the evaluation of ulcerative colitis. Radionuclide studies have a useful role in acute fulminant colitis when colonoscopy or barium enema study is contraindicated. Radionuclide studies are also useful in depicting disease activity and the extent of disease and in monitoring the response to therapy. Limitations of TechniquesAll imaging techniques lack specificity. Mucosal ulceration depicted on barium studies is nonspecific and encountered in a variety of colitides. Barium enema may precipitate toxic megacolon in severe cases. Generally, barium enemas can be performed safely only in mild cases. Thickening of the bowel wall, as seen on cross-sectional imaging (CT, MRI, and US), is nonspecific and is found in a variety of bowel conditions besides IBD. Increased radionuclide focal activity may be related to a variety of physiologic and pathologic conditions unrelated to ulcerative colitis. Motion artifacts can interfere with cross-sectional imaging. Although this is not a major problem with modern scanners, some investigators still use a hypotonic agent to decrease bowel peristalsis. DIFFERENTIALSBowel, Trauma Colitis, Pseudomembranous Colon, Adenocarcinoma Colon, Diverticulitis Colon, Polyposis Syndromes Colon, Polyps Crohn Disease Gastrointestinal Bleeding, Lower Mesenteric Ischemia Rectal Carcinoma Toxic Megacolon Tuberculosis, Gastrointestinal Other Problems to Be ConsideredAcute infective enterocolitis from infection due to Entamoeba histolytica (amebiasis), cytomegaloviral colitis, and Isospora, Salmonella, Shigella, or Yersinia species may present with similar radiologic features, especially on CT scans. Prolonged use of cathartics, especially cascara, over many years may lead to changes in the colon (cathartic colon) with the radiologic appearance of ulcerative colitis. In cathartic colon, the changes are more marked in the right hemicolon than in the left. The bowel is distensible with inconstant areas of bowel narrowing and loss of haustra. RADIOGRAPHFindingsPlain radiographic findings Plain radiographs frequently yield useful information that may serve as a guide to further clinical evaluation and imaging. The intraluminal gas pattern may show pseudopolyposis and deep ulcers. The colon may appear shortened and associated with loss of colonic haustra. Toxic megacolon is a complication of ulcerative colitis. The plain abdominal radiograph may show massive colonic dilatation associated with an abnormal mucosal contour. The dilatation is most pronounced in the transverse colon. Colonic perforation is another known complication of ulcerative colitis. Perforation may occur with or without a toxic megacolon. Pneumoperitoneum associated with a colonic perforation is usually massive. Fecal residue may be absent in inflamed bowel. Barium enema findings The findings on a barium enema examination vary with the stage and severity of disease. The radiographic changes may involve the whole colon, but when the disease is segmental, the left colon is usually involved. Rectal sparing is rare and thought to occur in 5% of patients. Skip lesions are unusual. The colon may appear narrow; this is often associated with incomplete filling due to colonic spasm and irritability. The earliest mucosal changes are best depicted on a good-quality double-contrast barium enema study. Before ulcers appear, mucosal edema produces a fine, granular appearance when the radiographs are seen en face. When ulcers first appear, the mucosa may have a fine, stippled appearance when seen en face. When mucosal ulcers become established and confluent, the mucosa is replaced by granulation tissue, and double-contrast enema study reveals a characteristic, coarsely granular appearance. In the acute and subacute phases of the disease, the ulcers may acquire a variety of shapes: collar-button ulcers occur with undermining of the ulcers, and double-tracking ulcers are longitudinally orientated and sometimes several centimeters long. Symmetrical thickening of haustral folds may produce the appearance of thumbprinting. Pseudopolyps are a consequence of severe mucosal disease and appear as multiple filling defects of varying sizes. These may develop rapidly and tend to persist, even when the ulcerative colitis is quiescent. Occasionally, mucosal bridges are formed between pseudopolyps, which may be radiologically demonstrable. With increased severity and duration of disease, the involved colon may become narrow, shortened, and loose in terms of its normal redundancy and haustral pattern. On lateral projections, rectal narrowing is easily demonstrated as increased retrorectal space. When the entire colon is involved, changes in the terminal ileum may be seen (backwater ileitis); this involves 4-25 cm of the terminal ileum. The ileocecal valve appears patulous. The mucosa is granular and usually associated with absent peristalsis. Benign strictures usually occur (1-11%) in patients with long-standing disease and are predominantly found in the left colon. Carcinomas that complicate ulcerative colitis are usually annular and may be difficult to differentiate from benign strictures. Often, however, malignant strictures are eccentric, with nodular narrowing and shouldered edges. Multiple carcinomas are not rare in the setting of ulcerative colitis. About 50% of these tumors are not be detected on clinical or radiologic examination; instead, they are diagnosed at colectomy or autopsy. Degree of ConfidenceAlthough many radiographic findings are nonspecific, many radiographic criteria of ulcerative colitis are typical if not pathognomonic. False Positives/NegativesThe radiologic findings of ulcerative colitis are nonspecific, and the diagnostic signs of various colitides overlap considerably. Similar radiographic signs may occur in infective diarrheas, Crohn disease, ischemic colitis, drug-induced colitis, and amebic colitis. Infective diarrhea is occasionally the presenting feature of IBD. CT SCANFindingsWith increased use of CT as a primary imaging modality for evaluating IBD, radiologists must be able to recognize CT features of ulcerative colitis. Although barium studies remain the principal tool for diagnosing and evaluating suspected IBD, CT may aid in differentiating ulcerative colitis and Crohn disease when results of barium studies are equivocal. High-resolution thin-section imaging of both the intraluminal and extraluminal components enables radiologists to detect and stage colonic pathology. CT is valuable for the detection and characterization of ulcerative colitis. CT typically demonstrates circumferential, symmetrical wall thickening with fold enlargement. Thickening of the colon wall (mean, 7.8 mm; standard deviation, 1.9) may be present, with inhomogeneous attenuation and a target appearance of the rectum and the proliferation of perirectal fat. The normal colonic wall has a maximal thickness of 3 mm with the lumen distended and 5 mm with the lumen collapsed. In comparison, Crohn colitis causes greater bowel wall thickening (mean, 11 mm; standard deviation, 5.1). This appears with homogeneous attenuation, fistula and abscess formation, and mesenteric abnormalities. The target sign is due to an inner ring of soft tissue attenuation representing mucosa, lamina propria, and enlarged muscularis mucosa; a middle ring of low attenuation resulting from widening and fatty infiltration or edema of the submucosa; and an outer soft tissue attenuation representing the muscularis propria. If the submucosa is fat-infiltrated, this is a sign of chronicity and more specific for IBD. This sign is best appreciated on the arterial phase of enhancement. It is a nonspecific sign also reported in Crohn disease and pseudomembranous colitis. Ulcerative colitis is typically left sided or diffuse and only rarely involves the right colon exclusively. In ulcerative colitis, wall thickening may be diffuse and symmetrical, whereas that in Crohn disease is eccentric and segmental with skip lesions. The proliferation of perirectal fat is a nonspecific sign and can be present in any of the colitides. Submucosal fat deposition is present significantly more often in ulcerative colitis (61%) than in Crohn colitis (8%). Mural thickening of the terminal ileum may be visualized in 10-25% of patients; this is due to backwash ileitis as a result of the reflux of colonic contents into the distal ileum. Abscesses and pseudodiverticula are not features of ulcerative colitis and occur almost exclusively in Crohn colitis. Degree of ConfidenceCross-sectional imaging plays a prominent role in the assessment of IBD of the colon. The clinical history, laboratory data, and extent of involvement are used with the radiographic results to reach a specific diagnosis. CT is preferred to MRI for assessing the extent of inflammatory disease in and beyond the bowel wall. An added benefit of CT over MRI is the fact that patients with abscesses or large fluid collections can undergo drainage while still in the CT scanner. CT and MRI can aid in the distinction between ulcerative colitis with minimal wall thickening and Crohn disease with marked wall thickening combined with skip lesions and fistula and/or abscess formation.1 Although many CT findings in ulcerative colitis are striking, they are not considered specific. Some features are helpful in suggesting a diagnosis of IBD, and specific features can indicate a single diagnosis of ulcerative colitis with a high degree of confidence. The halo sign typically occurs in ulcerative colitis. False Positives/NegativesIn ulcerative colitis, bowel thickening is a nonspecific finding and can be encountered in a variety of colitides and other pathologies of the bowel wall. The target sign is also nonspecific and has been reported with Crohn colitis. Mucosal ulceration is difficult to detect with CT. The target sign may be secondary to a hypoattenuating submucosal layer of fluid (nonspecific) or fat (chronic in origin and usually from IBD). Also, there is evidence that submucosal fat can be a normal variant. MRIFindingsGiovagnoni and associates used high-resolution MRI to study 16 resected rectosigmoid specimens of patients treated with total colectomy for severe ulcerative colitis. Six normal colon specimens were used as controls. A parallel study of the pelvis of 24 patients with proven ulcerative colitis was performed by using the same MRI system. Two radiologists qualitatively evaluated bowel wall thickening and the signal intensity of the mural layers in vivo and in vitro and compared the results with gross and microscopic findings. The in vitro results showed that MRI could depict all layers of the colonic wall. In ulcerative colitis specimens in particular, T1-weighted spin-echo MRI showed thickening and the peculiar abnormal hyperintensity of the mucosal and submucosal layers. The in vivo results confirmed the high signal intensity of the mucosal and submucosal layers. These findings were not observed in the control group, in which the superficial layers appeared low in intensity on T1-weighted spin-echo images. The authors' preliminary experience suggests that MRI should be considered a new imaging modality for detecting changes of the colon wall in ulcerative colitis. Magnetic resonance cholangiopancreatography (MRCP) seems to be a reliable, noninvasive imaging method for diagnosing and following up primary sclerosing cholangitis. The rapid acquisition with relaxation enhancement (RARE) sequence has shown the highest diagnostic accuracy of the T2-weighted sequences. Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble movingor straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape. Degree of ConfidenceTransmural assessment, sagittal imaging, and the lack of invasiveness are attractive features of MRI. Shoenut and associates examined 20 consecutive patients with first-time presentation of suspected IBD. All patients underwent both endoscopy with biopsy and MRI within a 3-day period, and the relative abilities of endoscopy and MRI in distinguishing ulcerative colitis from Crohn disease and in determining the severity of disease were compared. In 18 patients, ulcerative colitis or Crohn disease could be diagnosed with histologic specimens. Gadolinium-enhanced, fat-suppressed, T1-weighted, spin-echo MRI enabled correct diagnosis in 17 of these 18 patients. Endoscopy enabled correct diagnosis in 15 patients. Overall, MRI was not significantly better (P >.05) than endoscopy in distinguishing ulcerative colitis from Crohn disease. MRI permitted correct grading of the severity of inflammatory changes in 13 of 20 patients, and endoscopy did so in 11 cases. MRI and endoscopic findings were within one grade of the histologic findings in 7 patients each. No significant difference (P >.05) was found between MRI and endoscopy in terms of the estimation of disease severity (as determined from biopsy samples). Bowel wall thickness on MRIs had good correlation with the percentage of contrast enhancement (r = 0.61; P = .003). In this study, MRI was comparable to endoscopy in differentiating ulcerative colitis from Crohn disease and in assessing the severity of disease. False Positives/NegativesAn important differential diagnosis of ulcerative colitis is Crohn disease, though their differentiation on images is not always possible. Hansmann and associates evaluated the diagnostic role of hydro-MRI in 33 patients with suspected Crohn disease or ulcerative colitis. After colonic distention by means of rectal enema, breath-hold MRI was performed during bowel relaxation. Results were compared with the clinical diagnosis and the results of endoscopy, barium study, and histopathologic analysis. MRI enabled the correct diagnosis in all 24 patients with active Crohn disease. However, conversely, MRI results were positive in only 2 of 5 patients with ulcerative colitis. In 5 patients, IBD was excluded. No false-positive results occurred. The authors concluded that hydro-MRI was a reliable modality in the diagnosis of Crohn disease. In the differentiation of Crohn disease from ulcerative colitis, hydro-MRI seems to be a promising imaging procedure. ULTRASOUNDFindingsExcluding infective and toxic states, Crohn disease and ulcerative colitis are the most common causes of chronic large bowel inflammation. US features are nonspecific and include bowel wall thickening, which may involve both the hypoechoic muscular coat and the echogenic mucosa. There is longitudinally extending wall thickening, with decreased echogenicity and luminal narrowing. Localized perforation may lead to the formation of an abscess, which may be clinically silent if the patient is receiving steroid therapy. Several criteria have been described for the detection of Crohn colitis and ulcerative colitis. A water-filled colon may be used to get better definition of the large bowel mucosa. With Crohn colitis, the whole bowel wall is thickened; all layers are involved with edema, fibrosis, inflammation, and lymphangiectasis. On US, the wall is clearly thickened, hypoechoic, and homogeneous initially, but it may become inhomogeneous due to fat deposition. The layered anatomy of the bowel wall and the haustra are lost. The bowel becomes rigid, with diminished compressibility and peristalsis. The diameter of the wall is approximately 13 mm. In ulcerative colitis, the wall thickness is not as great and averages 7.8 mm. Early disease is confined to mucosa, the wall stratification is preserved, but haustra are lost. In Crohn disease and ulcerative colitis, the presence of Doppler parietal flow throughout the affected thickened segment indicates an acute condition. Similarly, an abnormally high mean portal velocity of 30-48 cm/s (normal, 15 ± 7 cm/sec) and an abnormally low resistive index of 0.58-0.78 (normal, 0.908-0.026) are detected in the superior mesenteric artery (SMA). These Doppler findings are known to revert to normal with successful therapy. Differentiation between ulcerative colitis and Crohn disease is important from a management viewpoint. The latter tends to be transmural disease, and the former tends to be a superficial inflammatory process of the mucosa. Endosonography (EUS) was expected to be effective in discriminating cases of otherwise indeterminate colitis. Efforts to demonstrate these changes with EUS have been largely disappointing, but EUS plays a limited role in discriminating ulcerative colitis from Crohn disease. On a more positive note, EUS evaluation of perirectal and perianal complications of Crohn disease has been demonstrated to be superior to fistulography and CT and equal or superior to MRI. Because accurate anatomic information is required to guide surgical therapy of these lesions, EUS has the potential to emerge as a powerful imaging tool in the management of perianorectal Crohn disease.2 Bru and associates prospectively compared the usefulness of hydrocolonic US and technetium-99m (99mTc) hexamethylpropylamine oxime (HMPAO)–labeled WBC scintigraphy in 68 patients with active IBD (34 ulcerative colitis and 34 Crohn disease), in 12 with inactive IBD, and in 10 control subjects.3 Patients with active disease underwent clinical assessment, hydrocolonic US, scintigraphy, and colonoscopy within 72 hours, whereas patients with inactive disease and control subjects underwent clinical examination and hydrocolonic US. Involvement of a colonic segment by active IBD was best defined by mucosal thickness greater than 1.5 mm, bowel wall thickness greater than 4 mm, mucosal irregularity, or the absence of haustra. Involvement of the terminal ileum was defined by bowel wall thickness greater than 4 mm. With these criteria, hydrocolonic US had 100% sensitivity in identifying patients with active IBD and a greater overall accuracy (87%) than scintigraphy (77%) in the assessment of disease extension. In addition, a hydrocolonic US activity index was strongly correlated with clinical and endoscopic activity indexes. The authors concluded that their study provides precise US criteria for the definition of bowel involvement by active IBD. Sigirci and associates evaluated Doppler US blood-flow parameters and spectral patterns in the inferior mesenteric artery (IMA) and SMA in patients with active and inactive (remission-phase) ulcerative colitis in 25 patients.4 They concluded that duplex Doppler US of the IMA and SMA can be used to evaluate inflammatory disease of the large bowel, to assess the extent of disease, and to document the response to therapy. Degree of ConfidenceVisualization of the upper abdomen and the bowel, in particular, is frequently compromised by the presence of gas within the bowel. To a certain extent, this can be overcome by performing US examinations in the morning, when bowel gas is at a minimum. Water can be used to distend the colon and provide an acoustic window, but many people swallow air when drinking, and this can cause further artifacts. US measurements of bowel wall thickness can provide a simple, noninvasive technique for monitoring IBD in children. Thickened and hypervascularized bowel wall are characteristic findings in IBD. A combination of B-mode and power Doppler US offers an additional noninvasive procedure for the determination of activity in patients with IBD. False Positives/NegativesMost bowel pathologies cause thickening of the bowel wall. On bowel examination, a target sign is usually seen. With this sign, a hypoechoic wall surrounds the echogenic mucosa, intraluminal mucous, air, and other bowel contents. This target may be round or oval (pseudo-kidney sign). Under normal physiologic conditions, the hypoechoic bowel wall measures less than 4 mm. With few exceptions, this 4-mm rule can be applied to the whole of the bowel. Under pathologic conditions, the bowel wall thickens symmetrically in target fashion. Alternatively, it may be thickened asymmetrically when the echogenic lumen is displaced to one side on a true cross-section; this is the atypical target sign. Most bowel pathology, whether inflammatory or neoplastic, can be inferred from the aforementioned signs. As with most imaging findings, these signs are nonspecific and only a differential diagnosis can be offered. US evidence of mural thickening of the bowel with a paucity of luminal content may be helpful in the detection of IBDs. However, the findings are nonspecific, and the differential diagnosis must be related to the specific segment of the bowel involved. NUCLEAR MEDICINEFindingsUntil recently, gallium-67 (67Ga) was the only radionuclide used in the scanning of IBD. However, recent developments in leukocyte labeling have largely replaced the use of gallium because of better dosimetry and resolution and a lower radiation burden to the patient. Jones and associates performed 67Ga citrate scanning in 9 patients with ulcerative colitis. In all patients, there was good correlation between the regional uptake of gallium and the extent and activity of disease. In 2 patients, scans were positive during an acute exacerbation and reverted to normal or near normal during clinical remission. In 1 patient in whom the colon was resected because of toxic dilatation, good correlation was found between pathologic and scintigraphic results. During an acute attack of ulcerative colitis, when colonoscopy or barium enema may be contraindicated, gallium scanning may be a noninvasive means of assessing the extent of colonic involvement. It may also be an alternative means of following the clinical course of the disease. With the availability of indium-labeled WBCs, radionuclide-imaging studies have a definite role in the diagnosis and staging of IBD. The indium-111 (111In) WBC study is particularly helpful in evaluating recurrent disease in patients with severe intercurrent diseases and in screening patients, without the need for barium examinations. Indium-111 oxine and 111In tropolone are neutral, nonpolar, lipophilic chelates that penetrate the cell membrane of leukocytes. Once inside the leukocytes, the 111In ion dissociates from the chelate and forms a relatively stable bond with cytoplasmic and nuclear proteins. There are a number of differences in the 2 chelating agents, but one of the most important is that 111In oxine cannot be used to label leukocytes in the presence of plasma because of the higher affinity of 111In for transferrin than for oxine. Indium-111 tropolone is a stronger chelating agent, and using it does not require the removal of plasma before cell labeling. Both types of 111In label all types of blood cells indiscriminately; therefore, the leukocytes must first be separated from the other cells. The result is a mixed population of labeled leukocytes, including neutrophils, monocytes, and lymphocytes; this is acceptable for most imaging. Labeling efficiencies on the order of 80-90% can be achieved with either agent. If the labeling efficiency is less than 40%, the cells should not be reinjected. Indium-111–labeled leukocytes are normally distributed to the spleen, liver, and bone marrow and transiently in the lungs. The accumulation of activity at sites other than these normal sites is suggestive of infection or inflammation. WBCs can be labeled with 99mTc. Technetium-99m HMPAO is a neutral, nonpolar, lipophilic agent that was originally developed for cerebral perfusion imaging. The compound is unstable and breaks down into a hydrophilic secondary complex. In its lipophilic form, 99mTc HMPAO can cross the cell membrane of leukocytes. Once within the cell, its structure is altered to the hydrophilic form, and 99mTc is trapped inside. Technetium-99m HMPAO leukocyte labeling can be performed in the presence of plasma and appears to have significant selectivity for granulocytes. As with 111In-labeled leukocytes, 99mTc-labeled leukocytes are localized in the spleen, liver, and bone marrow and transiently in the lungs. False-positive diagnosis of bowel inflammation is possible with 99mTc-labeled leukocytes, as normal localization occurs in the bowel at about 3-4 hours in adults and earlier in children. This localization is associated with sloughing of leukocytes into lumen of the GI tract. In addition, activity is seen in the urinary tract and occasionally within the gallbladder. Fasting for 2-4 hours prior to imaging may reduce hepatobiliary excretion and subsequent bowel activity, especially in children. The 1-hour images demonstrate lung activity but no activity in the GI system. Studies have indicated that imaging with 99mTc-labeled leukocytes may be more sensitive than imaging with 111In-labeled leukocytes for detecting and determining the extent of IBD, especially in the small bowel. [18F]-Fluorodeoxyglucose positron tomography has recently been used in the diagnosis of pediatric IBD. This technique appears to provide adequate information in patients with suspected IBD.5 Degree of ConfidenceRadionuclide-labeled WBC scanning using 111In is an accurate, quantitative, and noninvasive method for assessing the degree of bowel inflammation in IBD and its response to therapy. For this study, fecal collection or total body counts of radioactivity can be used. More recently, the use of 99mTc HMPAO WBC scanning was introduced. This has several advantages over the 111In scanning, including a reduction in the radiation dose and better image resolution. The 99mTc HMPAO WBC technique can be used in combination with single-photon emission CT (SPECT), which allows visualization of the entire bowel separate from overlying structures. 99mTc HMPAO WBC SPECT has now been computerized and automated to permit measurement of segmental and total bowel uptake. This method could potentially become the criterion standard for an objective assessment of the response of disease activity in Crohn disease and ulcerative colitis.6 Arndt and associates prospectively compared scanning using 99mTc HMPAO WBCs with that using 111In-labeled granulocytes to assess the presence and location of active IBD in 14 patients. The 2 examinations were performed within 2 weeks of each other. Scintigraphically concordant positive or discordant segments were evaluated by means of radiologic or endoscopic examination performed within 14 days. When bowel segments were compared, concordance was found for 102 (91.8%) of 111 segments with 1-hour WBC images and 3-hour granulocyte images. For 5 of 5 WBC-positive and granulocyte-negative segments, it could be proven that the WBC result was caused by active disease. 99mTc-labeled WBC scintigraphy detected active disease in 4 more patients than did scanning with 111In-labeled granulocytes (11 and 7 patients, respectively). Tc-labeled WBCs was superior in the assessment of active disease, especially in small-bowel segments. The authors concluded that early imaging at 1 hour after the injection of 99mTc-labeled WBCs can reliably replace 111In-granulocyte scintigraphy in patients with IBD because the radiopharmaceutical is available on a daily basis. Thus, the radiation burden to the patient is reduced, and cell separation is simpler and less time-consuming. Tolia and associates compared 111In-labeled WBC scanning and colonoscopy in 19 children and adolescents with chronic IBD to study the correlation between the 2 diagnostic modalities versus histologic diagnosis.7 Seven patients had ulcerative colitis, 10 had Crohn disease, and 2 had no specific diagnosis after evaluation. The sensitivity of 111In scanning was 18%, its specificity was 62.5%, and its accuracy for colonic disease was only 37%. In comparison, the sensitivity and specificity of colonoscopy were 100% and 57%, respectively, and its accuracy was 84%. The data suggest that the usefulness of scans is limited to patients in whom standard diagnostic procedures are contraindicated. Additionally, the authors suggested that the visual diagnostic impression must be confirmed with colonoscopy and histologic diagnosis. Peters and associates compared 99mTc-labeled WBCs with 111In-labeled WBCs and found that the 2 agents provided similar clinical information in 27 of 30 patients.8 Of the 3 in whom the information differed, 1 received 111In-labeled granulocytes, which were considered to be functionally suboptimal. In the other 2, who had IBD, the scans showed different distributions of abnormal bowel activity. The authors concluded that, with respect to granulocyte kinetics and clinical data, leukocytes labeled with 99mTc HMPAO were comparable to granulocytes labeled with 111In tropolonate. Poitras and associates performed 111In-labeled WBC scanning in 10 patients with ulcerative colitis and in 39 patients with Crohn disease involving the small intestine (25 cases) and/or the colon (17 cases).9 Radionuclide uptake by the gut was seen in 84% of the patients with active inflammation. The results of radionuclide uptake were compared with radiologic, endoscopic, or surgical findings. In two thirds of the patients, 111In leukocyte scanning of the abdomen enabled accurate evaluation of the extent of disease (sensitivity, 68%). False-positive results were not seen in small bowel disease (specificity, 100%), but they were observed on 4 occasions in the colon (specificity, 86%). The intensity of radionuclide uptake could not be correlated with the clinical activity of the disease, as evaluated by the Crohn disease activity index. The authors concluded that the results of radionuclide scanning were not superior to those of conventional techniques used to detect and localize IBD and that radionuclide methods cannot replace these techniques. However, the authors went on to emphasize that the simplicity of radionuclide methods and their lack of complications make them useful in evaluating the extent and distribution of inflammation in some patients, mainly those with severe disease in whom standard diagnostic procedures are contraindicated. False Positives/Negatives111In-labeled WBCs accumulate nonspecifically at sites of inflammation and/or infection. The differential diagnosis for accumulation of 111In-labeled WBCs involving the abdomen most commonly includes Crohn disease, ulcerative colitis, diverticulitis, ischemic or infarcted bowel, phlegmon, and wound infection. False-positive results can be secondary to swallowed leukocytes, enteric tubes, or a GI bleed. False-positive results may also occur with 99mTc-labeled WBCs with physiologic uptake, biliary and urinary excretion, and delayed normal bowel excretion. Saverymuttu and associates reported 2 cases of colonic carcinoma that appeared as suspected IBD and in which 111In-labeled granulocytes were localized.10 Histology revealed an acute inflammatory infiltrate in these tumors. These results indicate that 111In-labeled granulocyte scanning has limitations in the diagnosis of IBD. ANGIOGRAPHYFindingsTsuchiya and associates performed selective superior and inferior mesenteric angiography in 25 patients with ulcerative colitis.11 Vascular changes on angiograms were compared with the clinical features. These vascular changes were not correlated with the duration of illness or the extent of involvement. Vascular changes in large vessels, such as increased diameter of the IMA, were better correlated with the severity or activity of illness. However, in some cases, microcirculatory changes of small vessels of the intestinal wall (eg, capillary blush or loss of normal tapering of vasa recta) still remained in remission of this disease. The authors assumed that this microcirculatory disturbance plays an important role in the pathophysiology of ulcerative colitis. Momoshima and associates administered intra-arterial prednisolone infusion therapy to 37 patients with ulcerative colitis who had an inadequate response to conventional medical therapies.12 The prednisolone infusions were delivered via the SMA and IMA. The therapy was effective in 31 (57%) of 54 infusions, including 3 of 5 cases of toxic megacolon. The effectiveness of the therapy was well correlated with the clinical assessment of disease activity. The caliber of the IMA was positively correlated with the effectiveness of the therapy. As the intra-arterial infusion of prednisolone led to improvements in ulcerative colitis, the authors concluded that this mode of therapy should be considered in patients with ulcerative colitis, particularly in severe cases. Hiramatsu and associates performed angiography in 11 patients with ulcerative colitis.13 They injected prednisolone directly into the superior and IMAs in 10 patients. Hypervascularity of the affected regions was a common finding, but early venous filling was noted in only 5 of 11 cases. Good results were obtained with intra-arterial steroid injections. Angiography is a valuable tool in the diagnosis and therapy of hemorrhage from the large bowel from ulcerative colitis and other causes. Degree of ConfidenceBrahme and Hildell evaluated the diagnostic yield of angiography in 116 patients with Crohn disease. Angiographic abnormalities were found in over 90%. Many angiographic features were nonspecific; only the zoning sign and the presence of paraintestinal mesenteric neovasculature were considered diagnostic. Crohn disease could be distinguished from ulcerative colitis in only 30% of the cases. The authors concluded that angiography was a diagnostic adjunct to barium studies and revealed the presence of lesions and their extent. They suggested that this feature was particularly important in suspected postoperative recurrences of Crohn disease. They suggested that angiography was a potential aid in the differential diagnosis of doubtful cases of inflammatory and malignant bowel disease. False Positives/NegativesAngiographic findings are nonspecific, and both false-positive and false-negative results can occur. INTERVENTIONThe risk of carcinoma increases with ulcerative colitis in patients with a chronic form of the disease. Surgery should be contemplated only when (1) 2 biopsy samples evaluated by 2 pathologists confirm the findings and (2) low-grade dysplasia is present in a raised lesion. As yet, no evidence suggests that regular endoscopic screening of patients with ulcerative colitis improves their survival. The treatment of ulcerative colitis relies on initial medical management with corticosteroids and anti-inflammatory agents, such as sulfasalazine, coupled with symptomatic treatment with anti-diarrheal agents and rehydration. Surgery is contemplated when medical treatment fails or when a surgical emergency (eg, perforation of the colon) is present. Surgical options include total colectomy (panproctocolectomy) and ileostomy, total colectomy, and ileoanal pouch reconstruction or ileorectal anastomoses. In an emergency situation, subtotal colectomy with end-ileostomy is recommended. Medical/Legal Pitfalls
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