| Abstract|| |
Regional enteritis (Crohn disease) may present a diagnostic problem that needs to be solved by clinicians practicing in areas known to be endemic for tuberculosis. The similarity in clinical presentation between the two disorders makes it difficult to reach a diagnosis. Furthermore, the use of steroids in treating patients with Crohn disease may be harmful if the underlying diagnosis is Tuberculosis. This article is aimed to help physicians to distinguish Crohn disease from intestinal Tuberculosis. The treating physician would be able to use and interpret different diagnostic modalities tailored to the history and physical examination. The use of ASCA, a new serological marker, in the diagnosis of Crohn disease may facilitate the management of such patients
Keywords: Crohn disease, regional enteritis, Tuberculosis, ASCA, ANCA, diagnosis.
|How to cite this article:|
Khalil MZ. Diagnosis of regional enrteritis (Crohn disease). Saudi J Gastroenterol 2003;9:6-10
The clinical presentation of Crohn disease (CD) has been known to clinicians since the description of the disease by Crohn in 1932  . However, Dalziel reported an earlier description of patients with interstitial ileitis in 1913  . Over the past decade, there has been an improvement in the early detection and management of CD. Looking at the natural history and clinical features of CD, it was found that there was an average interval of 35 month from onset of symptoms to diagnosis, and the disease was confined to the terminal ileum in 14% of patients . When the disease is presenting with a typical history of prolonged diarrhea, abdominal pain, weight loss, and fever, associated with prior or concomitant history of perianal disease, the diagnosis may not represent a dilemma to the treating clinician, particularly, in the presence of a family history of inflammatory bowel disease (IBD). However, there is extensive differential diagnosis of CD when the presentation is ambiguous. Of interest here, is intestinal tuberculosis (TB) which can mimic CD of the ileum and cecum, especially in countries known to be endemic for TB.
One major concern in establishing a solid diagnosis of CD, is the use of steroids, which may lead to a flare up if the underlying disease is actually, TB. Therefore, the revelation of CD, is a task that might cause a struggle to the treating physician, when exclusion of intestinal TB is of strong differential. In this article, the emphasis will focus on how to reach a safe diagnosis of regional enteritis (CD) in patients who may have intestinal TB.
| History and physical examination|| |
A through history and detailed physical examination should be the first step in revealing features more suggestive of CD than TB. Perianal disease was reported to occur in 36% of patients with CD  . The commonest presentations were perianal abscess (29.5%), anal fissure (27.6%), and low anal fistula (26.7%)  . Anal lesions preceded the onset of intestinal symptoms in 19 percent of cases .
Extraintestinal manifestations of CD were observed in one fourth of patients and should be carefully looked for , . Among the common extraintestinal manifestations are; arthritis, clubbing, erythema nodosum, pyoderma gangrenosum, aphthous, ulcers, uveitis, episcleritis, scleromalacia, corneal ulcers, primary sclerosing cholangitis and bile duct carcinoma. Joints were involved in 23%, skin in 15% and mouth and eye each in 4%  .
Less commonly; urinary oxalate stones, renal tubular damage, peripheral neuropathy, myelopathy, and acute pancreatitis were recognized. Some of the extraintestinal manifestations may precede CD, although the majority accompanies the underlying disease and are related to its activity.
A family history of inflammatory bowel disease is strongly suggestive of CD in-contrast to TB. Recent studies have shown the increased risk of inflammatory bowel disease in relatives of patients with Crohn disease and ulcerative colitis, where first degree relatives are approximately 3 to 20 times more likely to develop the disease ,,,,.
| Radiological evaluation|| |
Radiology defines the baseline distribution, nature, and severity of the disease  . Requesting a radiological investigation, in the evaluation of a patient suspected to suffer from CD, should be tailored to the clinical presentation.
| Barium Studies|| |
Small bowel barium enema study is relatively noninvasive, well tolerated, and produces a radiographic record that can be saved for review and comparison with subsequent studies  . The earliest inflammatory changes consist of edema and ulceration. The mucosal edema may appear as blunting, flattening, thickening, distortion, or straightening of the valvule conniventes in the small bowel. Edema of deeper layers of the bowel wall leads to separation of barium-filled bowel loops.
The characteristic cobblestone appearance is created from barium tracking in both longitudinal and transverse directions of denuded areas formed by progressive ulceration that may coalesce in either the small or large bowel. Continuing inflammation often leads to fibrotic stenosis and, ultimately, to frank obstruction. However, marked narrowing, as manifested radiologically by the classic "string sign" in the terminal ileum, is often due primarily to spasm rather than to fibrosis.-Fistulas may be seen as simple isolated tracts or complex stellate conglomerations spreading out in diverse directions
These characteristic radiological features of CD, if found, are not one hundred percent diagnostic as they have been reported in a patient suffering from terminal ileitis secondary to mycobacterium paratuberculosis [Figure - 1] .
| Ultrasonography|| |
Ultrasonography has limited value in the evaluation of patients with established CD. It may be an adjuvant in the assessment of undiagnosed right lower quadrant pain by detecting appendicitis, tuboovarian pathology, ectopic pregnancy, and pelvic inflammatory disease. Therefore, it remains to be of unproven value in revealing Crohn disease from intestinal tuberculosis.
| Computed tomography (CT)|| |
Abdominal CT can demonstrate marked transmural thickening and is also the modality of choice for diagnosing extramural complications. Fistulas not seen on barium studies may be revealed by minute quantities of intramural air by CT scan. Furthermore, needles can be guided by CT to obtain materials for cytological or hitological examination either by aspiration or biopsy.
| Magnetic resonance imaging (MRI)|| |
In the evaluation of intra-abdominal Crohn disease, MRI remains inferior to abdominal CT scan. However, MRI may prove superior for demonstrating pelvic lesions such as ischiorectal abscesses and for clarifying the relationship of perirectal fistulas to the levator ani .
| White cell scan|| |
Technetium- 99 m white cell scan (Tc-WCS) is used to detect inflammation and similar lesions in which granulocytes accumulate. Tc 99 m-white cell is injected into patients intravenously, along with leukocytes taken from the patient's own blood. The mixture binds to sites of inflammation, and images are taken using a gamma camera [Figure - 2].
A positive Tc-WCS result indicates the presence of an inflammatory process of the gut, whereas a negative test result does not rule out intestinal inflammation, especially when the latter is of moderate degree  . However, due to patient preference combined with the reported accuracy of white cell scanning, the usefulness of this test in the diagnosis of IBD may be of value  . Furthermore, Tc-WCS may be a complementary technique to colonoscopy for the detection, localization, and characterization of inflammation of the terminal ileum, particularly when lesions are inaccessible to evaluation by colonoscopy because of technical limitations, such as scars, strictures, inflammation  .
| Endoscopy|| |
Intubation of the ileocecal valve during colonoscopy allows examination and biopsy of the terminal ileum. However, isolated aphthous ulcers in the ileum in the absence of any other evidence of Crohn disease may be nonspecific. Moreover, endoscopic appearance correlates poorly with clinical remission, either in response to drug therapy or postoperatively , . Endoscopy should be used as complementary to radiology. It is a useful tool for obtaining biopsy of strictures, mass lesions, or filling defects seen on barium enema.
| Histology|| |
Transmural inflammation, submucosal edema, lymphoid hyperplasia, deep fissuring ulcers and sinus tracts, or fibrosis are among the diagnostic histologic features of Crohn disease. Mucosal biopsies obtained endoscopically may lack some of these features due to its superficial nature. Skip areas may be noted on multiple mucosal biopsy specimens, or occasionally a single mucosal biopsy fragment will reveal histologically normal mucosa only millimeters away from fully developed crypt abscesses.
The presence of granulomas, most commonly located in the submucosa, or sometimes be found in the lamina propria as well, may complicate the issue of differentiating Crohn disease from intestinal TB. Therefore, intestinal biopsies are usually confirmatory in Crohn disease rather than diagnostic  .
| Antibody tests|| |
The diagnosis of inflammatory bowel disease depends on a combination of clinical, radiographic, endoscopic, and histologic criteria that bears imperfect specificity. The value of antiSaccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (PANCA) to increase diagnostic accuracy has been evaluated in several studies. ASCA are specific markers for CD. A reasonably inexpensive, easy and reproducible assay to assess for antibodies to S cerevisiae has been developed. Using a cutoff for positivity of 15 binding units, this test had a specificity of 100% for ruling out Crohn disease and a lower (60%) sensitivity compared with ulcerative colitis  . The positive predictive values of the ANCA assay combined with the ASCA assay for ulcerative colitis and Crohn disease are high enough to be clinically use fult  . In a group of patients with indeterminate colitis (IC), results showed that ASCA positive p-ANCA negative predicts CD in 80% of patients  .
Moreover, the presence of ASCA in unaffected relatives might point toward a genetic predisposition to CD . ASCA and p-ANCA assays are highly disease specific for CD and UC, respectively. These serological tests can assist clinicians in diagnosing and categorizing patients with IBD and may be useful in making therapeutic decisions. One study showed that children who were P-ANCA negative but ASCA positive were more likely to have Crohn disease (49% sensitivity and 97% specificity)  .
The generation of ASCA may be mainly related to genetic influences although environmental factors may also play a certain role. It has been shown by one study that these antibodies are found in 25% of first-degree relatives of patients with CD  .
Furthermore, the finding of increased serum ASCA titers in patients with Crohn disease suggests that Saccharomyces cerevisiae may play a role in the pathophysiology of this condition  . However, testing for ANCA and ASCA together did not achieve sensitivity necessary for population screening  .
| Conclusions|| |
The diagnosis of Crohn disease may represent a clinical problem that needs to be solved by clinicians practicing in areas known to be endemic for tuberculosis. The similarity in clinical presentation between the two disorders makes a solid ground for diagnosis should be reached before treatment is initiated. For practical purposes, [Table - 1] can be used to help physicians to distinguish CD from intestinal TB. A wise clinician would be able to use and interpret different diagnostic modalities tailored to the history and physical examination. A current and growing evidence may suggest the use of ASCA, a new serological marker in the diagnosis of Crohn disease.
| References|| |
|1.||Crohn B. Ginzburg, L, Oppenheimer G. Regional enteritis: A pathological and clinical entity. JAMA 1932; 99:1323. |
|2.||Dalziel T K. Chronic interstitial enteritis. BMJ 1913; 2: 1068. |
|3.||Mekhjian HS, Switz DM, Melnyk CS, Rankin GB, Brooks RK. Clinical features and natural history of Crohn disease. Gastroenterology 1979; 77: 898-906. [PUBMED] |
|4.||Rankin GB, Watts HD, Melnyk CS, Kelley ML Jr. National Cooperative Crohn Disease Study: extraintestinal manifestations and perianal complications. Gastroenterology 1979; 77: 914-20. |
|5.||Platell C, Mackay J, Collopy B, Fink R, Ryan P, Woods R. Anal pathology in patients with Crohn disease. Aust N Z J Surg 1996; 66: 5-9. [PUBMED] |
|6.||Pescatori M, Interisano A. Basso L, et al. Management of perianal Crohn disease. Results of a multicenter study in Italy. Dis Colon Rectum 1995; 38: 121-4. |
|7.||Das KM. Relationship of extraintestinal involvements in inflammatory bowel disease: new insights into autoimmune pathogenesis.Dig Dis Sci 1999; 44: 1-13. [PUBMED] [FULLTEXT]|
|8.||Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn disease and ulcerative colitis: a study of 700 patients. Medicine (Baltimore) 1976; 55: 401-12. [PUBMED] |
|9.||Satsangi J, Grootscholten C, Holt H, Jewell DP. Clinical patterns of familial inflammatory bowel disease. Gut 1996; 38: 738-41. [PUBMED] [FULLTEXT]|
|10.||Roth MP, Petersen GM, McElree C, Vadheim CM, Panish JF, Rotter JI. Familial empiric risk estimates of inflammatory bowel disease in Ashkenazi Jews. Gastroenterology 1989; 96: 1016-20. [PUBMED] |
|11.||Monsen U, Brostrom O, Nordenvall B, Sorstad J, Hellers G. Prevalence of inflammatory bowel disease among relatives of patients with ulcerative colitis. Scand J Gastroenterol 1987; 22: 214-8. |
|12.||Fielding JF. The relative risk of inflammatory bowel disease among parents and siblings of Crohn disease patients. J Clin Gastroenterol 1986; 8: 655-7. [PUBMED] |
|13.||Lee JC, Lennard-Jones JE. Inflammatory bowel disease in 67 families each with three or more affected first-degree relatives. Gastroenterology 1996; 111: 587-96. [PUBMED] [FULLTEXT]|
|14.||Marshak, R, and Lindner, A. Regional enteritis. In Marshak, R. and Lindner, A. (eds.), Radiology of the Small Intestine, 2nd ed. Philadelphia, W. B. Saunders, 1976: 179. |
|15.||Waye J D. X-ray or endoscopic examination for initial evaluation and follow-up in patients with colonic inflammatory bowel disease. In Korelitz, B I. and Sohn, N. (eds.), Management of Inflammatory Bowel Disease. Chicago, Mosby-Year Book 1992; 105. |
|16.||John Hermon-Taylor, Nick Barnes, Chris Clarke, Caroline Finlayson. Mycobacterium paratuberculosis cervical lymphadenitis, followed five years later by terminal ileitis similar to Crohn disease. BMJ 1998; 316: 449-53. |
|17.||Koelbel, G, Schmiedl, U, Majer, M. C, et al. Diagnosis of fistulae and sinus tracts in patients with Crohn disease: Value of MR imaging. AJR 1989; 152: 999. |
|18.||Cucchiara S; Celentano L; de Magistris TM; Montisci A; lula VD; Fecarotta S Colonoscopy and technetium-99m white cell scan in children with suspected inflammatory bowel disease. J Pediatr 1999; 135: 727-32. |
|19.||Richard L Nelson, Alan Schwartz, Dan Pavel. Assessment of the usefulness of a diagnostic test: A survey of patient preference for diagnostic techniques in the evaluation of intestinal inflammation. BMC Medical Research Methodology 2001; 1: 5. |
|20.||Martin Charron, J. Fernando del Rosario, and Samuel Kocoshis. Distribution of Acute Bowel Inflammation Determined by Technetium-Labeled White Blood Cells in Children with Inflammatory Bowel Disease. Inflammatory Bowel Diseases 1998; 4. |
|21.||Olaison, G, Smedh, K, Sjodahl, M. Natural course of Crohn disease after ileocolic resection: Endoscopically visualized ileal ulcers preceding symptoms. Gut, 1992; 33: 331. |
|22.||Gaing, A A., Geders, J M, Cohen S., Siegel, J H. Endoscopic management of primary sclerosing cholangitis. Review and report of an open series. Am. J. Gastroenterol 1993; 88: 2000. |
|23.||Blomberg, B, Rolny P, Jarnerot, G. Endoscopic treatment of anastomotic strictures in Crohn disease. Endoscopy 1991; 23: 195. |
|24.||Bernstein CN, Orr K, Blanchard JF, Sargent M, Workman D. Development of an assay for antibodies to Saccharomyces cerevisiae: Easy, cheap and specific for Crohn disease. Can J Gastroenterol 2001; 15: 499-504. [PUBMED] |
|25.||Sandborn WJ, Loftus EV, Colombel JF, et al. Evaluation of serologic disease markers in a population-based cohort of patients with ulcerative colitis and Crohn disease. Inflamm Bowel Dis 2001; 7: 192-201. [PUBMED] |
|26.||Joossens S, Reinisch W , Vermeire S, et al. The value of serologic markers in indeterminate colitis: a prospective follow-up study. Gastroenterology 2002; 122: 1242-7. |
|27.||Annese V, Andreoli A, Andriulli A, et al. Familial expression of anti-Saccharomyces cerevisiae Mannan antibodies in Crohn disease and ulcerative colitis: a GISC study. Am J Gastroenterol 2001; 96: 2407-12. [PUBMED] [FULLTEXT]|
|28.||Ruemmele FM, Targan SR, Levy G, Dubinsky M. Braun J, Seidman EG. Diagnostic accuracy of serological assays in pediatric inflammatory bowel disease. Gastroenterology 1998; 115: 822-9. |
|29.||Seibold F, Stich O, Hufnagl R, Kamil S, Scheurlen M. Anti-Saccharomyces cerevisiae antibodies in inflammatory bowel disease: a family study. Scand J Gastroenterol 2001;36: 196-201. [PUBMED] |
|30.||Oshitani N, Hato F, Matsumoto T, et al. Decreased anti-Saccharomyces cerevisiae antibody titer by mesalazine in patients with Crohn disease. J Gastroenterol Hepatol, 2000; 15: 1400-3. |
|31.||Hoffenberg EJ, Fidanza S, Sauaia A. Serologic testing for inflammatory bowel disease. J Pediatr, 1999; 134: 447-52. |
Mohamed Zakaria Khalil
King Khalid University Hospital, P.O. Box 2529, Riyadh 11461
Source of Support: None, Conflict of Interest: None
[Figure - 1], [Figure - 2]
[Table - 1]