Home | E-Submission | Sitemap | Editorial Office |  
Clin Endosc > Volume 49(4); 2016 > Article
Lee and Lee: Endoscopic Diagnosis and Differentiation of Inflammatory Bowel Disease

Abstract

Patients with inflammatory bowel disease have significantly increased in recent decades in Korea. Intestinal tuberculosis (ITB) and intestinal Behcet’s disease (BD), which should be differentiated from Crohn’s disease (CD), are more frequent in Korea than in the West. Thus, the accurate diagnosis of these inflammatory diseases is problematic in Korea and clinicians should fully understand their clinical and endoscopic characteristics. Ulcerative colitis mostly presents with rectal inflammation and continuous lesions, while CD presents with discontinuous inflammatory lesions and frequently involves the ileocecal area. Involvement of fewer than four segments, a patulous ileocecal valve, transverse ulcers, and scars or pseudopolyps are more frequently seen in ITB than in CD. A few ulcers with discrete margins are a typical endoscopic finding of intestinal BD. However, the differential diagnosis is difficult in many clinical situations because typical endoscopic findings are not always observed. Therefore, clinicians should also consider symptoms and laboratory, pathological, and radiological findings, in addition to endoscopic findings.

INTRODUCTION

Inflammatory bowel disease (IBD) is a chronic and idiopathic inflammatory disease of the digestive tract showing a remitting and relapsing disease course. Ulcerative colitis (UC) and Crohn’s disease (CD) are two major forms of IBD. The number of patients with IBD has rapidly increased in recent years and is increasingly prominent in Korea [1]. However, many clinicians do not yet fully understand the clinical and endoscopic characteristics of IBD so that diagnosis is frequently delayed or incorrect in many cases. Accurate diagnosis of IBD is an important problem in Korea due to the higher prevalence of intestinal tuberculosis (ITB) and intestinal Behcet’s disease (BD) than in the West [2,3].
Guidelines for diagnosis of IBD were established by the IBD Study Group of the Korean Association for the Study of Intestinal Diseases in 2009 [3-6]. In this review, we delineate typical endoscopic findings and the differential diagnostic features of UC, CD, ITB, and intestinal BD based on these guidelines.

TYPICAL ENDOSCOPIC FINDINGS OF INFLAMMATORY BOWEL DISEASE

Ulcerative colitis

The inflammation involves the rectum in most cases and spreads proximally. The typical endoscopic findings in patients with UC include edematous mucosa, erythema, loss of vascular markings, and mucosal friability [4]. More severe cases may be associated with erosions, ulcers, and spontaneous bleeding. Luminal narrowing and pseudopolyps may occur due to chronic inflammation, which results in mucosal atrophy (Fig. 1) [7-9]. Focal inflammation around the appendiceal orifice is observed in up to 75% of patients with UC [10].
However, these typical findings are not always present. A Korean study revealed that atypical distribution of inflammation was seen in 20% of newly diagnosed UC patients during initial colonoscopy: 3.3% had segmental UC with rectal sparing and 15.8% presented with segmental skip lesions without appendiceal orifice inflammation [11]. Although inflammation in UC patients is mostly limited to the colon, ileal inflammation (backwash ileitis) may infrequently be observed [12]. In this case, physicians should consider small bowel evaluation to differentiate CD from UC [13].

Crohn’s disease

Typical endoscopic findings in CD include discontinuous distribution of longitudinal ulcers (defined as ≥4 to 5 cm ulcers in the Japanese criteria), cobblestone appearance, and/or small aphthous ulcerations arranged in a longitudinal fashion (Fig. 2) [5,14]. A Korean study reported longitudinal ulcers in 37.2%, cobblestone appearance in 23.9%, and aphthous ulcers in 59.3% of newly diagnosed CD cases. Non-caseating granuloma, a biopsy feature suggestive of CD, may be noted in only 13% to 36% of patients with CD so that sensitivity of biopsy is low [15].
Esophagogastroduodenoscopy is not routinely recommended in CD patients unless upper gastrointestinal symptoms are present [5]. Gastroduodenal CD presents with nonspecific lesions such as erosions, erythema, or ulcers [16]. A bamboo joint-like appearance can be seen on endoscopy, characterized by swollen, longitudinal folds traversed by erosive fissures or linear furrows on the lesser curvature of the gastric body and cardia [17].

Intestinal tuberculosis

ITB frequently involves the ileocecal area and ascending colon. Endoscopic findings of ITB may include transverse ulcers, nodules with inflammatory changes of surrounding mucosa, pseudopolyps, and/or distorted and strictured ileocecal valves (Fig. 3) [3,18,19]. Although the typical histologic feature of caseating granuloma, positive acid-fast staining, and/or isolation of Mycobacterium tuberculosis from the culture of biopsy specimens can confirm ITB, these findings are present in fewer than 50% of patients [20,21]. Therefore, acquisition of more than three biopsy samples from the margin and base of ulcers is recommended to increase the diagnostic yield [3].

Intestinal Behcet’s disease

Typical endoscopic findings in intestinal BD are a few, large, round, deep, and discrete ulcers with elevated margins in the ileocecal area (Fig. 4). Other atypical findings such as aphthous ulcers, irregular/geographic-shaped ulcers with focal distribution, and diffuse ulceration can be present in patients with intestinal BD [6,22].

DIFFERENTIAL DIAGNOSIS OF INFLAMMATORY BOWEL DISEASE

Ulcerative colitis and other causes of enterocolitis

The differential diagnosis of UC includes infectious colitis, ischemic colitis, colitis due to drugs, radiation colitis, and solitary rectal ulcer syndrome [4,23]. A history of preceding abdominal pain, medication use, radiation therapy, or straining during defecation can be helpful [4].
Clinicians should always keep in mind that there is no specific endoscopic finding of UC. Infectious colitis can present with endoscopic features similar to those of UC. Thus, to make the correct diagnosis, onset and duration of symptoms should be considered together. Microbiological culture can also be helpful for differentiating UC from infectious colitis. Indeed, in a multinational web-based survey conducted by the Asian Organization for Crohn’s and Colitis, more than half of Asian gastroenterologists reported always or usually performing microbiological culture for suspected UC [24].

Ulcerative colitis and Crohn’s disease

UC mostly presents with rectal inflammation and continuous lesions, while CD presents with discontinuous inflammatory lesions that frequently involve the ileocecal area. Shallow and indiscrete ulcers that involve only the mucosa, with edematous and erythematous changes in the surrounding area may suggest UC [22]. CD can involve not only the colon but also the small bowel, and frequently presents with deep ulcers. The deep ulcers with a longitudinal array create a cobblestone appearance. Sparing of the rectum, presence of perianal disease, and occurrence of strictures and fistulas suggest CD.
Use of serologic markers may help in the differential diagnosis of UC and CD [25,26]. Anti-Saccharomyces cerevisiae antibodies (ASCA) can be detected in 35% to 50% of CD patients, but in only 1% of patients with UC [26]. On the other hand, perinuclear antineutrophil cytoplasmic antibodies (pANCA) are detected more frequently in patients with UC. The sensitivity of pANCA+ for UC was reportedly 55.3%, and ASCA+ in combination with pANCA– resulted in 54.6% sensitivity for detection of CD [25]. Considering the relatively low sensitivity, serologic test can be the adjunctive tool when differentiation between CD and UC is clinically difficult (Table 1).

Crohn’s disease and intestinal tuberculosis

The presence of longitudinal ulcers is a typical endoscopic finding in CD, whereas transverse ulcers are common in ITB (Table 2). However, since these typical findings are not always present, it is often difficult to differentiate between the two diseases [23]. In a Korean study that assessed the diagnostic value of various colonoscopic findings in CD and ITB, anorectal lesions, longitudinal ulcers, aphthous ulcers, and cobblestone appearance were seen frequently in CD, whereas involvement of fewer than four segments, a patulous ileocecal valve, transverse ulcers, and scars or pseudopolyps were observed commonly in ITB [27]. Using these parameters, the correct diagnosis was made in 87.5% of patients, with a positive predictive value of 94.9% for CD and 88.9% for ITB, respectively. However, this analysis method is still not validated, and further studies are needed.
The typical histologic finding of caseating granuloma and positive acid-fast staining are seen in fewer than 30% of ITB patients [28], but chest X-ray and interferon-γ assay may aid in the diagnosis of ITB. In fact, 67% of ITB patients had active pulmonary TB in a Korean study [29]. Therefore, chest X-ray is an essential test in ITB. Interferon-γ assay may also be useful as a supplementary diagnostic tool for ITB. A recent Korean study reported that 66% of patients with ITB had a positive interferon-γ assay (QuantiFERON-TB Gold test), compared to 9.7% of patients with CD [30].
If accurate diagnosis of the two diseases remains unclear despite the above methods, performing follow-up colonoscopy after empirical anti-TB therapy can be helpful [3].

Crohn’s disease and intestinal Behcet’s disease

A Korean study suggested an algorithm for the differential diagnosis of CD and intestinal BD according to endoscopic features. Ulcer shape, distribution, number, margins, and border contours, and the presence of aphthous, cobblestone, perianal, and strictured lesions enabled correct diagnosis of intestinal BD or CD in 92% of a study population [31]. Among these parameters, the most sensitive finding indicative of intestinal BD was the absence of a cobblestone appearance, and the most specific was a round ulcer shape. In addition, distribution patterns in patients with intestinal BD are more focal than in patients with CD. Therefore, a round ulcer or focally distributed lesions in the intestinal tract can suggest intestinal BD.
Another Korean study proposed simple criteria for the diagnosis of intestinal BD using systemic and colonoscopic features. Five or fewer lesions, oval shape, deep penetration, discrete border, and ileocecal location were regarded as typical ulcerations in BD. Overall, the positive predictive value and diagnostic accuracy using these criteria were 86.1% and 91.1%, respectively [32].

CONCLUSIONS

Colonoscopy is the principal test for diagnosing IBD. Clinicians can accurately diagnose most cases by fully understanding the typical endoscopic findings. In some cases, however, it is difficult to differentiate IBD due to an atypical presentation. Therefore, not only endoscopic features but also clinical symptoms, as well as laboratory, pathological, and radiological findings should be considered.

NOTES

Conflicts of Interest: The authors have no financial conflicts of interest.

Fig. 1.
Typical endoscopic features of ulcerative colitis. (A) Mild: mucosal erythema, fine granularity, decreased vascular marking. (B) Moderate: marked erythema, loss of vascular marking, erosions. (C) Severe: ulcers. (D) Severe: spontaneous bleeding. (E) Luminal narrowing with pseudopolyps.
ce-2016-090f1.gif
Fig. 2.
Typical endoscopic features of Crohn’s disease. (A) Longitudinal ulcers, (B) cobblestone appearance, (C) aphthous ulcers showing longitudinal array.
ce-2016-090f2.gif
Fig. 3.
Typical endoscopic features of intestinal tuberculosis. (A) Transverse ulcers, (B) deformed and patulous ileocecal valve, (C) pseudopolyps.
ce-2016-090f3.gif
Fig. 4.
Typical endoscopic feature of intestinal Behcet’s disease. A large, round, deep, and discrete ulcer in the terminal ileum.
ce-2016-090f4.gif
Table 1.
Differential Diagnosis of UC and CD
Characteristic UC CD
Rectal involvement Almost always Frequent
Small bowel involvement Rare Frequent
Continuous lesions Always Infrequent
Depth of ulceration Mucosa Deeper than mucosa
Cobblestone appearance No Yes
Stricture Rare Frequent
Fistula No Frequent
Perianal lesions No Frequent
pANCA ++ +
ASCA + ++

UC, ulcerative colitis; CD, Crohn’s disease; pANCA, perinuclear antineutrophil cytoplasmic antibodies; ASCA, anti-Saccharomyces cerevisiae antibodies.

Table 2.
Endoscopic Characteristics of CD and ITB
Characteristic CD ITB
Involvement of ICV Common Usually, strictured and patulous ICV
Involvement of colon ≥4 Segments, especially terminal ileum and ICV <4 Segments, especially ICV and ascending colon
Ulcers Longitudinal Transverse
Cobblestone appearance Frequent Rare
Aphtous lesions Frequent Rare
Perianal lesions Frequent Rare
Scars/pseudopolyps + ++

CD, Crohn’s disease; ITB, intestinal tuberculosis; ICV, ileocecal valve.

REFERENCES

1. Yang SK, Yun S, Kim JH, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea, 1986-2005: a KASID study. Inflamm Bowel Dis 2008;14:542-549.
crossref pmid
2. Suzuki Kurokawa M, Suzuki N. Behcet’s disease. Clin Exp Med 2004;4:10-20.
crossref pmid
3. Kim YS, Kim YH, Lee KM, Kim JS, Park YS; IBD Study Group of the Korean Association of the Study of Intestinal Diseases. Diagnostic guideline of intestinal tuberculosis. Korean J Gastroenterol 2009;53:177-186.
pmid
4. Choi CH, Jung SA, Lee BI, et al. Diagnostic guideline of ulcerative colitis. Korean J Gastroenterol 2009;53:145-160.
pmid
5. Ye BD, Jang BI, Jeen YT, et al. Diagnostic guideline of Crohn’s disease. Korean J Gastroenterol 2009;53:161-176.
pmid
6. Cheon JH, Shin SJ, Kim SW, et al. Diagnosis of intestinal Behcet’s disease. Korean J Gastroenterol 2009;53:187-193.
pmid
7. Waye JD. The role of colonoscopy in the differential diagnosis of inflammatory bowel disease. Gastrointest Endosc 1977;23:150-154.
crossref pmid
8. Waye JD. Endoscopy in inflammatory bowel disease: indications and differential diagnosis. Med Clin North Am 1990;74:51-65.
crossref pmid
9. Jalan KN, Walker RJ, Sircus W, McManus JP, Prescott RJ, Card WI. Pseudopolyposis in ulcerative colitis. Lancet 1969;2:555-559.
crossref pmid
10. D’Haens G, Geboes K, Peeters M, Baert F, Ectors N, Rutgeerts P. Patchy cecal inflammation associated with distal ulcerative colitis: a prospective endoscopic study. Am J Gastroenterol 1997;92:1275-1279.
pmid
11. Park SH, Yang SK, Park SK, et al. Atypical distribution of inflammation in newly diagnosed ulcerative colitis is not rare. Can J Gastroenterol Hepatol 2014;28:125-130.
crossref pmid pmc pdf
12. Haskell H, Andrews CW Jr, Reddy SI, et al. Pathologic features and clinical significance of “backwash” ileitis in ulcerative colitis. Am J Surg Pathol 2005;29:1472-1481.
crossref pmid
13. Stange EF, Travis SP, Vermeire S, et al. European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. Gut 2006;55 Suppl 1:i1-i15.
crossref pmid pmc
14. Yao T. New criteria for the diagnosis of Crohn’s disease. Stomach Intest 1996;31:451-464.

15. Park JB, Yang SK, Myung SJ, et al. Clinical characteristics at diagnosis and course of Korean patients with Crohn’s disease. Korean J Gastroenterol 2004;43:8-17.
pmid
16. Kang MS, Park DI, Park JH, et al. Bamboo joint-like appearance of stomach in Korean patients with Crohn’s disease. Korean J Gastroenterol 2006;48:395-400.
pmid
17. Yokota K, Saito Y, Einami K, et al. A bamboo joint-like appearance of the gastric body and cardia: possible association with Crohn’s disease. Gastrointest Endosc 1997;46:268-272.
crossref pmid
18. Naga MI, Okasha HH, Ismail Z, El-Fatatry M, Hassan S, Monir BE. Endoscopic diagnosis of colonic tuberculosis. Gastrointest Endosc 2001;53:789-793.
crossref pmid
19. Singh V, Kumar P, Kamal J, Prakash V, Vaiphei K, Singh K. Clinicocolonoscopic profile of colonic tuberculosis. Am J Gastroenterol 1996;91:565-568.
pmid
20. Hoshino M, Shibata M, Goto N, et al. A clinical study of tuberculous colitis. Gastroenterol Jpn 1979;14:299-305.
crossref pmid pdf
21. Lee YJ, Yang SK, Myung SJ, et al. The usefulness of colonoscopic biopsy in the diagnosis of intestinal tuberculosis and pattern of concomitant extra-intestinal tuberculosis. Korean J Gastroenterol 2004;44:153-159.
pmid
22. Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002;347:417-429.
crossref pmid
23. Lee HS, Choe J, Lee HJ, et al. Change in the diagnosis of inflammatory bowel disease: a hospital-based cohort study from Korea. Intest Res 2016;14:258-263.
crossref pmid pmc
24. Kim ES, Chen M, Lee J, Lee CK, Kim YS. Diagnosis of inflammatory bowel disease in Asia: the results of a multinational web-based survey in the 2nd Asian Organization for Crohn’s and Colitis (AOCC) meeting in Seoul. Intest Res 2016;14:224-230.
crossref pmid pmc
25. Reese GE, Constantinides VA, Simillis C, et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol 2006;101:2410-2422.
crossref pmid
26. Nikolaus S, Schreiber S. Diagnostics of inflammatory bowel disease. Gastroenterology 2007;133:1670-1689.
crossref pmid
27. Lee YJ, Yang SK, Byeon JS, et al. Analysis of colonoscopic findings in the differential diagnosis between intestinal tuberculosis and Crohn’s disease. Endoscopy 2006;38:592-597.
crossref pmid pdf
28. Alvares JF, Devarbhavi H, Makhija P, Rao S, Kottoor R. Clinical, colonoscopic, and histological profile of colonic tuberculosis in a tertiary hospital. Endoscopy 2005;37:351-356.
crossref pmid pdf
29. Kim KM, Lee A, Choi KY, Lee KY, Kwak JJ. Intestinal tuberculosis: clinicopathologic analysis and diagnosis by endoscopic biopsy. Am J Gastroenterol 1998;93:606-609.
crossref pmid
30. Kim YS, Kim YH, Kim WH, et al. Diagnostic utility of anti-Saccharomyces cerevisiae antibody (ASCA) and interferon-γ assay in the differential diagnosis of Crohn’s disease and intestinal tuberculosis. Clin Chim Acta 2011;412:1527-1532.
crossref pmid
31. Lee SK, Kim BK, Kim TI, Kim WH. Differential diagnosis of intestinal Behcet’s disease and Crohn’s disease by colonoscopic findings. Endoscopy 2009;41:9-16.
crossref pmid
32. Cheon JH, Kim ES, Shin SJ, et al. Development and validation of novel diagnostic criteria for intestinal Behçet’s disease in Korean patients with ileocolonic ulcers. Am J Gastroenterol 2009;104:2492-2499.
crossref pmid
Editorial Office
Korean Society of Gastrointestinal Endoscopy
#817, 156 Yanghwa-ro(LG Palace, Donggyo-dong), Mapo-gu, Seoul, 04050, Korea
TEL: +82-2-335-1552   FAX: +82-2-335-2690    E-mail: ksge@gie.or.kr
Copyright © Korean Society of Gastrointestinal Endoscopy. All rights reserved.