Zsolt Tarján

The epidemiology and the pathogenesis of inflammatory bowel disease

The etiology of inflammatory bowel disease (IBD) is still unknown. However, a satisfactory solution cannot be far away. IBD actually encompasses two diseases, i.e. Crohns disease (CD) and ulcerous colitis (UC). These diseases resemble each other so closely that they cannot be distinguished even pathologically, but differ from each other sufficiently to regard them as independent entities. Epidemiological observations may be helpful in identifying the true causative factors of this evasive disease. Geographically, the prevalence of the disease has a slope from North to South and, to a lesser degree, from West to East. The Western-Eastern discrepancy can be attributed to a difference in Western life styles. The incidence of the disease has been increasing world-wide of late, but its spread has been slowing down in highly affected countries. Racial and ethnic relations in different populations and immigration studies offer interesting data which can reflect genetic, inherited, environmental and behavioural factors. The disease seems to have a characteristic racial-ethnic distribution: the Jewish population is highly susceptible everywhere, but its prevalence in that population nears that of the domestic society in which they live. In Hungary, the Roma (Gypsies) have a considerably lower prevalence than the average population. This can be attributed to a genetic or environmental influence. According to age, the onset of the disease occurs more often in the second or the third decade of life, but there also is another peak in the 60s. Regarding sexual distribution, there is a slight preponderance of colitis ulcerosa in men and of Crohns disease in women. It may correspond to the stronger auto-immune affection in the process of Crohns disease. Environmental factors and behavioural influences also are investigated. Diet, the role of the early ages, smoking habits and the influence of hormonal status and drugs are viewed as useful contributing factors in the manifestation of the disease. Genetic studies show that one-fourth of IBD patients have an affected family member. HLAB27 histocombatibility also plays an important, but not determining role in the development of the disease. Genetic factors seem to have a stronger influence in Crohns disease than ulcerative colitis. The existence of multiple sclerosis-IBD families may reflect the common genetic background or the similar microbial effect as well. A great number of bacterial and viral factors has been suspected of being infectious factors in IBD, mostly in CD. Mycobacteria, Yersinia, Campylobacter, Clostridium, Clamidias, etc. as well as bacteria and some viruses such as herpes and rotavirus and the primary measles virus. None of them has been proven as a real and exclusively pathogenic factor. Immunological background has an important function in the manifestation of the disease. If an individual has a genetic susceptibility to infections, the down regulation of an inflammation in the bowel wall does not occur in a proper way. This initiates the auto-immune process which is a self-increasing cycle. Extra-intestinal manifestations of IBD are of high importance because they can not only follow intestinal symptoms, but precede them by years. Hepatic and biliary disturbances (primary sclerosing cholangitis), are the most serious complications. Mucocutaneous manifestations can be the first appearance of the main disease (in the mouth). Auto-immune consequences (erythema nodosum) or complications caused even by the therapy can occur. Ocular and musculoskeletal manifestations supposedly have the same genetic background and often precede the intestinal symptoms. Considering the epidemiological, genetic and immunological data, we can conclude that ulcerative colitis and Crohns disease are heterogeneous disorders of mutifactorial etiology in which hereditary (genetic) and environmental (microbial, behaviour) factors interact to produce the disease.

Ultrasound in Crohn’s disease of the small bowel

OBJECTIVE The purpose of this work is to prospectively evaluate high resolution ultrasonography with graded compression in the ability to detect Crohns disease of the small bowel (CDSB) together with its complications and activity signs, compared with enteroclysis, CT and immunoscintigraphy in the mirror of the final diagnosis. METHODS AND MATERIAL In a series of 73 consecutive patients, who were referred for enteroclysis with suspected Crohns disease of the small bowel computed tomography (CT), ultrasound (US), immunoscintigraphy with 99mTc labeled monoclonal antigranulocyte antibody (AGAb) examinations were performed within 10 days from each other. For the final evaluation the diagnosis of CDSB was based on combination of clinical and enteroclysis findings (73 cases) and in 17 cases additional surgical and pathological data were available. The results of other modalities were blinded to the radiologists performing and reading out the exams. The diagnostic values of each modality was assessed also in those 18 patients, who had early Crohns disease. In the group of 43 patients with proven CDSB who had all the four imaging modalities, the modalities were compared in their ability to demonstrate various pathological conditions related to CD. Increased (>500 ml/min) flow measured by Doppler US in the superior mesenteric artery and increased color signs in the gut wall seen by power Doppler sonography were compared to CDAI. RESULTS Of the 73 patients the combination of enteroclysis and clinical tests demonstrated CDSB in 47. The sensitivity, specificity and accuracy of ultrasound were 88.4, 93.3 and 90.4%, respectively. Enteroclysis was the most accurate method. CT was more sensitive than US, but less specific. The accuracy of US, CT and scintigraphy were similar. In the group of 18 patients, who had early CDSB, the sensitivity of US decreased to only 67%, CT and scintigraphy had higher values. Intra- and perimural abscesses, and sinus tracts were also more frequently visualized by US, especially if they were small. US was superior than CT in detecting stenoses and skip lesions, but inferior to enteroclysis. US and CT detected more fistulas, than enteroclysis. Compared to CT, US detected more cases with mesenteric lymphadenopathy, equal cases with abscesses and free peritoneal fluids. In detecting mesenteric inflammatory proliferation CT, and in detecting colonic involvement CT and immunoscintigraphy were slightly superior than graded compression US. Patterns of mural stratification detected by ultrasound correlated well with the enteroclysis severity stages. There was only 59% agreement between increased superior mesenteric artery flow detected by Doppler sonography and CDAI, and 60.5% agreement between increased number of Color pixels in the gut wall measured by power Doppler and increased CDAI. CONCLUSION High resolution graded compression sonography is a valuable tool for detecting small intestinal Crohns disease. It has similar diagnostic values as CT. However in early disease the sensitivity substantially decreases. In known Crohns disease for following disease course, evaluating relapses and extramural manifestations US is an excellent tool. Doppler and Power Doppler activity measurements do not correlate well with the more widespread clinical activity index.

Spiral CT colonography in inflammatory bowel disease

OBJECTIVE Most of the studies on virtual colonoscopy are dealing with the role of detecting colorectal polyps or neoplasms. We have undertaken this study to evaluate the value of CT colonography in patients with colonic Crohns disease. METHODS AND MATERIAL Five patients (three males, two females, 23-51 years, mean age 42 years) with known (4) or suspected (1) Crohns disease of the colon underwent fiberoptic colonoscopy and CT colonography in the same day or during a 1-week period. The images were evaluated with the so called zoomed axial slice movie technique and in some regions intra- and extraluminal surface shaded and volume rendered images were generated on a separate workstation. The results were compared to those of a colonoscopy. RESULTS The final diagnosis was Crohns disease in four patients and colitis ulcerosa in one. Total examination was possible by colonoscopy in two cases, and with CT colonography in all five cases. The wall of those segments severely affected by the disease were depicted by the axial CT scans to be thickened. The thick walled, segments with narrow lumen seen on CT colonography corresponded to the regions where colonoscopy was failed to pass. Air filled sinus tracts, thickening of the wall of the terminal ileum, loss of haustration pseudopolyps and deep ulcers were seen in CT colonography. Three dimensional (3D) endoluminal views demonstrated pseudopolyps similar to endoscopic images None of the colonoscopically reported shallow ulcerations or aphtoid ulcerations or granular mucosal surface were observed on 2- or 3D CT colonographic images. CONCLUSION CT colonography by depicting colonic wall thickening seems to be a useful tool in the diagnosis of Crohns colitis, which could be a single examination depicting the intraluminal, and transmural extent of the disease.

The role of nuclear medicine in inflammatory bowel disease. A review with experiences of aspecific bowel activity using immunoscintigraphy with 99mTc anti-granulocyte antibodies

UNLABELLED The diagnosis of inflammatory bowel disease (IBD) needs a complex diagnostic work-up. Beside verifying the disease itself, it is fundamental to assess disease extent and activity and to detect associated complications, to find the most effective treatment and for follow up. Scintigraphy with radiolabelled leukocytes is able to provide a complete survey of the whole intestinal tract, both the small and large bowel, and detects septic complications successfully with negligible risk. Radionuclide procedures are useful in establishing or ruling out IBD in patients with intestinal complaints, in assessing disease severity, and in the evaluation of extraintestinal septic complications. Widely available radionuclide procedures are discussed, i.e. scintigraphy by 111Indium oxime or 99mTechnetium HMPAO labelled white blood cells and immunoscintigraphy with 99mTc anti-granulocyte antibodies. Advantages and disadvantages of all three methods are stressed out. PATIENTS AND METHODS The immunoscintigraphies with 99mTc anti-granulocyte antibodies (ANTI-GRANULOCYTE(R) BW 250/183) of 27 patients with suspicion of IBD were retrospectively analysed. Planar anterior and posterior images were obtained 4 and 24 h postinjection, respectively. The bowel was divided into six segments and the activity was visually graded with reference to bone marrow in each segments. The scans were compared with the results of radiological and endoscopical investigations. The diagnosis of IBD was proved or ruled out by means of enteroclysis, large bowel enema or endoscopy. RESULTS In the 27 patients, 74 bowel segments with increased activity were detected. In the case of 30 segments in 16 patients, bowel inflammation was revealed by the other methods (true positives). In the case of 44 bowel segments, no underlying bowel inflammation could be verified, and these activities were regarded as aspecific activity. We could not differentiate between true positive and aspecific activity based on scan pattern or intensity. DISCUSSION These findings of aspecific bowel activity using imuunoscintigraphy are in contrast with the results of former studies, while the existence of non-specific activity decreases the reliability of the method. Based on the literature and our experiences, we conclude that 99mTc HMPAO labelling should be the method of choice for the investigation of IBD patients.

Carcinoma arising in enterocutan fistulae of Crohn's disease patients: description of two cases

Rarely, carcinoma arises from the fistulous tract of Crohns disease. Adequate radiological examination often produces misleading pseudonegative findings. We reported two cases of fistula cancers treated with infliximab. The short time-span between the administration of this drug and the diagnosis of cancer makes the correlation between the two unlikely.