Chronic Idiopathic Inflammatory Bowel Disease Research Articles

Development of Candida albicans Colitis in a Child Undergoing Steroid Therapy for Ulcerative Colitis

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease (IBD) characterized by colonic mucosal inflammation with a relapsing/remitting course. The primary treatment of mild to moderate active UC is sulfasalazine or mesalazine (5-ASA), and the secondary therapy for more severe dise

Effects of Ayurvedic treatment on forty-three patients of ulcerative colitis

Ulcerative colitis is a chronic idiopathic inflammatory bowel disease with a relapsing nature. It is a very challenging disease affecting a patient during the most active period of his life i.e. 20 to 40 years of age. The main features are ano-rectal bleeding with increased frequency of bowel evacuation, general debility and with abnormal structural pathology in the descending colon, particularly sigmoid colon. In modern medical science, there is no permanent curative and safe treatment for this disease. This study can be helpful for reducing the need of steroids and surgical processes in the patients of ulcerative colitis. A clinical study of 43 patients of ulcerative colitis has been conducted at the O.P.D. (outdoor patient department) and I.P.D. (indoor patient department) of the P D Patel Ayurveda Hospital, Nadiad. They were given Udumbara kvatha basti with oral Ayurveda medicaments including Kutaj ghan vati, Udumbara kvatha, and combination of Musta, Nagakesara, Lodhra, Mukta panchamrut rasa for a one-month period. Results were analyzed statistically by using the ‘t’ test. In this study, it was observed that the symptoms and signs, daily dose of steroids and other anti-inflammatory drugs were reduced by more than 75% with a highly significant result. The hemoglobin level was also increased.

Low prevalence of antibodies to cyclic citrullinated peptide in patients with inflammatory bowel disease regardless of the presence of arthritis

Crohn's disease (CD) and ulcerative colitis are chronic idiopathic inflammatory bowel diseases (IBD) often associated with axial and/or peripheral arthritis. Antibodies against cyclic citrullinated peptide (anti-CCP) are highly specific for rheumatoid arthritis, whereas their role in IBD remains unclear. Antitumour necrosis factor-alpha agents such as infliximab (IFX) may achieve and maintain remission of both IBD and rheumatoid arthritis; however, they may also trigger the development of various autoantibodies and autoimmune manifestations. This study aims at assessing the prevalence and clinical associations of anti-CCP antibodies in IBD patients with and without arthritis under either conventional treatment or IFX. Eighty four consecutive patients with CD [36 (42.8%) patients on IFX scheduled maintenance therapy (5 mg/kg intravenously every 8 weeks) and 48 (57.2%) on nonbiological treatment] and 50 patients with ulcerative colitis [20 (40%) patients on IFX (as described earlier) and 30 (60%) on nonbiological treatment] were evaluated. Among these 134 patients, 48 (35.8%) patients presented with concurrent arthritis. Ninety healthy individuals matched for sex and age with the IBD patients served as controls. Anti-CCP antibodies were detected using a commercially available enzyme-linked immunosorbent assay. Anti-CCP antibodies were detected in one CD patient on IFX maintenance therapy without evidence of arthritis. Neither the presence of arthritis nor treatment with IFX was associated with the presence of anti-CCP antibodies in IBD patients. Our data suggest that the prevalence of anti-CCP antibodies is very low in IBD patients regardless of the presence of arthritis and/or of IFX treatment.

P280 - Faecal calprotectin remains stable in inactive Crohn's disease patients

P280 - Faecal calprotectin remains stable in inactive Crohn's disease patients

P281 - The prevalence of antibodies against cyclic citrullinated peptide (anti-CCP) is low in patients with inflammatory bowel disease with or without arthritis

P281 - The prevalence of antibodies against cyclic citrullinated peptide (anti-CCP) is low in patients with inflammatory bowel disease with or without arthritis

What histologic features best differentiate Crohnʼs disease from ulcerative colitis?

The differential diagnosis between untreated ulcerative colitis (UC) and Crohn’s disease (CD) in resected specimens is usually not difficult. UC is a diffuse, continuous mucosal disease that begins in the rectum and spreads variably to the proximal colon. The disease is worse distally. The ileum is not involved. Granulomas, fissures, and transmural lymphoid aggregates are not present. CD shows segmental distribution with variable disease severity (worse proximal) and variable rectal involvement. The ileum is involved in up to 40% of the patients. Granulomas, unrelated to mucin or foreign bodies, and fissures may be present. Fibromuscular obliteration and nerve fiber hyperplasia in the submucosa and transmural lymphoid aggregates are common. In specimens from patients operated on for severe (fulminant) colitis, a definite diagnosis can be difficult because of overlapping features. These cases are classified as “colitis of uncertain type — etiology” (indeterminate colitis).1 The differential diagnosis between UC and CD is important in these patients because an ileal pouch anal anastomosis is often recommended. In CD this type of operation may be less appropriate. Transmural lymphoid aggregates (specificity: 90%; positive predictive value: 62%), granulomas in the subserosa, and submucosal nerve fiber hyperplasia with ganglionitis all favor CD.2 The endoscopic biopsy diagnosis of UC and CD remains a problem. Many features useful for the diagnosis when surgical resection specimens are available are not present or are nonspecific when only the mucosa and superficial submucosa are available. Additionally, medical treatment changes the typical disease patterns. The two diseases share features and neither disease has a pathognomonic finding present in every case of the one and absent in every case of the other. The relative absence of discriminating features can partly be solved by analysis of multiple endoscopic biopsies from different areas of the colon and ileum.3 This allows conclusions about the distribution of the disease, the focal nature of inflammation in the same area, and the presence of areas of sparing. Discontinuous disease is a major indicator that the underlying condition is unlikely UC.4 Stepwise biopsies also provide information about the variability of the disease (UC is worse distally). Ileal involvement favors CD. Ileitis in UC is present only when active total disease involves the ileocecal valve in continuity with distal disease. Full colonoscopic biopsy series provide a correct diagnosis in 64% of cases for CD and 74% for UC, increasing to 96% with the addition of clinical information. (5) The clinical presentation can be atypical and a precise diagnosis remains difficult in early-onset disease (2–6 weeks after the first symptoms), in children, especially young children below the age of 12, and in patients with associated liver disease (hepatitis, primary sclerosing cholangitis).1 These patients can be classified temporarily as colitis, type unclassified (IBDU). The microscopic criteria applicable to endoscopic biopsy specimens for the distinction of inflammatory bowel disease (IBD) from other forms of colitis and of CD from UC include a combination of architectural and inflammatory features and other lesions. Architectural abnormalities are crypt distortion (nonparallel, variable diameter, cystic), crypt branching, crypt shortening, decreased crypt density, and irregular mucosal surface. Inflammatory features are transmucosal increase in lamina propria cellularity (basal plasmacytosis accumulation of lymphocytes and plasma cells between the bases of crypt and the muscularis mucosae or close to the muscularis mucosae) and neutrophils. Neutrophils are mainly an indicator of disease activity. Other lesions include a change in epithelial mucin content, abnormalities of the muscularis mucosae, and metaplasia (pseudopyloric metaplasia in the ileum and Paneth cell metaplasia in the colon). Abnormal architecture and basal plasmacytosis distinguish between chronic idiopathic IBD (present) and other causes of colitis (absent). In this regard, diverticular disease associated colitis is a differential diagnostic problem.6,7 These features may not be present at the initial onset of the disease. Plasmacytosis increased from 38% in biopsies obtained 1–15 days following onset of symptoms to 89% in biopsies obtained after 121–300 days. Architectural abnormalities increased from 0%–78%.8 Metaplasia occurs mainly in longstanding disease. After recovery with or without treatment, basal plasmacytosis and architectural abnormalities may decrease. Repeat endoscopy with biopsy and comparative study From the Department of Pathobiology, University Hospital, Leuven, Belgium. Copyright © 2008 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.20598 Published online in Wiley InterScience (www.interscience.wiley.com).

Enteric nervous system abnormalities in inflammatory bowel diseases

Various studies have described abnormalities of the enteric nervous system (ENS) in tissue samples from patients with chronic idiopathic inflammatory bowel diseases (IBD). The distribution of density of the different cell types of the ENS was however not studied in a systematic way. The aim of this study was to examine the density of neurons, enteroglial cells and interstitial cells of Cajal (ICC) in the different plexuses of the ENS in samples from patients with Crohn's disease (CD), ulcerative colitis (UC) and controls. Tissue samples from 16 patients with CD (ileum) and 16 patients with UC obtained in involved and non-involved areas were studied using immunohistochemistry with antibodies directed against neuron-specific enolase, S100, C-Kit and CD3. Sections were analysed blindly by two pathologists and the number of positive cells was counted for each type. Overall, an increase was noted for neuronal cell bodies, enteroglia and ICC in the deep muscular plexus in CD. In uninvolved areas of CD patients, the number of enteroglial cells was decreased. In UC, an increase of ICC in the muscularis propria and enteroglial cells was observed in diseased tissue. The study confirms the presence of abnormalities of the different cells of the ENS in IBD. The presence of lesions in samples from uninvolved areas, such as a reduction of enteroglia, supports a pathogenetic role of the ENS.

Lymphocytic, collagenous and other microscopic colitides: Pathology and the relationship with idiopathic inflammatory bowel diseases

Collagenous colitis and lymphocytic colitis are the two major conditions characterized by chronic watery diarrhoea, without endoscopic or radiological lesions, but with histological abnormalities and therefore considered as "microscopic colitis". The histology of colonic biopsies shows inflammation of the mucosa, and either thickening of the subepithelial collagen band or an increase of lymphocytes in the surface epithelium. Different variant forms have been reported under separate names. These are probably not specific entities. The incidence of microscopic colitis is slightly less than the incidence of chronic idiopathic inflammatory bowel diseases (IBD). Microscopic colitis and IBD are clearly different entities. The relation between both entities is weak but double. Biopsy samples from patients with IBD may mimic the features of lymphocytic or collagenous colitis, both in the initial onset and during follow-up. In the large majority of these cases, endoscopy shows or has shown mucosal lesions. In rare cases, however, a double diagnosis was made. Certain patients, usually of older age, presented first with a microscopic, usually collagenous colitis and developed subsequently genuine ulcerative colitis.

Dysplasia-associated mass or lesion (DALM) and sporadic adenomas in patients with chronic idiopathic inflammatory bowel disease

Dysplasia-associated mass or lesion (DALM) can occur in longstanding idiopathic inflammatory bowel disease, particularly in patients with ulcerative colitis who have had episodes of severe pancolitis over many years. Such patients also develop sporadic adenomas at the same rate as the general population. These cases illustrate features that may be used to distinguish these diseases. In DALM, there is an irregular glandular architecture, positive nuclear p53 staining, negative nuclear beta catenin staining and negative Bcl2 staining. In sporadic adenomas, the glandular architecture is regular, p53 nuclear staining is negative, there is usually strong nuclear staining for beta catenin and positive Bcl2 staining. In the past, a diagnosis of DALM was an indication for panproctocolectomy, but local endoscopic resection and surveillance is sufficient if there is no flat dysplasia in the background colon.

The expression of innate immunity genes in Italian Crohn disease patients.

Crohn' disease (CD) is a chronic idiopathic inflammatory bowel disease characterized by the interaction of both hereditary and environmental factors. Intestinal flora and pathogens such as bacteria, viruses and fungi, are thought to be the first step leading to an inflammatory status, which is subsequently amplified in genetically susceptible patients thus triggering the disease. Since the innate immune system is believed to be very important in regulating the flora of the gastrointestinal tract, we decided to study the influence of two important molecules of the innate immune system in CD. Frozen intestinal biopsies from 49 Crohn patients and 10 healthy individuals were collected at the gastroenterology unit of Children's Hospital Burlo Garofolo in Trieste and innate immunity gene expression was evaluated by using both in situ RT-PCR and quantitative PCR. We have analyzed the expression and localization of both MBL2 and DEFB1 genes in intestinal biopsies of Italian Crohn patients by in situ RT-PCR and quantitative PCR. DEFB1 is expressed equally in all subjects. Importantly, MBL2 transcripts were upregulated in CD patients compared to healthy controls. MBL2 expression in controls is normally extremely low, detectable only by quantitative PCR with a Taqman probe. We demonstrated the MBL2 and DEFB1 expression in intestinal biopsies of patients suffering from CD. Our results showed that the MBL2 gene is expressed by cells in the basal lamina, whilst DEFB1 is expressed by epithelial cells.

Diverticular Disease–Associated Segmental Colitis

Diverticular disease-associated segmental colitis is a unique variant of chronic colitis limited to segments of the left colon that harbor diverticula. Histologically, this disease mimics chronic idiopathic inflammatory bowel disease and can be indistinguishable from ulcerative colitis or Crohn's colitis on histologic grounds alone. Patients typically present with hematochezia and cramping abdominal pain, and colonoscopic evaluation reveals inflammatory changes limited to the segment of bowel containing the diverticula, with rectal sparing. Although this disease does not appear to be an unusual form of diverticulitis but possibly an immunologically mediated process, many patients respond to treatment directed toward diverticulitis. A subset of patients requires immunosuppressive therapy and/or surgery, and a small subset progresses to develop classic ulcerative colitis. Because of the histologic overlap with ulcerative colitis and occasionally Crohn's colitis, it is essential that endoscopists provide a full description of the macroscopic appearance of the inflammatory changes at endoscopy, such as limitation to a segment of diverticular disease, so that the pathologist can provide a more informative interpretation of the biopsy.

Eosinophilic Granulomatous Gastroenterocolitis and Hepatitis in a 1-year-old Male Siberian Husky

A case of eosinophilic granulomatous gastroenterocolitis and hepatitis in a 1-year-old male Siberian Husky is described. The dog presented with a history of diarrhea, weakness, lethargy, and anorexia of several months' duration. Hematologic and biochemical examinations, abdominal ultrasonography, computer tomography, and exploratory laparotomy were performed. Histopathologic examination of full-thickness biopsies from the gastrointestinal tract and liver revealed the presence of eosinophilic granulomatous lesions in the submucosa and tunica muscularis of stomach, jejunum, ileum, colon, and liver. Infectious agents were not detected by light microscopic and electron microscopic examination or by immunohistochemistry. On the basis of the findings, it is concluded that the disease in this dog represents an unusual manifestation of chronic idiopathic inflammatory bowel disease.

Intestinal Low-grade Tubuloglandular Adenocarcinoma in Inflammatory Bowel Disease

Chronic idiopathic inflammatory bowel disease (IBD) with extensive colonic involvement predisposes to the development of colorectal adenocarcinoma. Among the types of cancer occurring in this setting is an unusually well-differentiated low-grade tubuloglandular adenocarcinoma (LGTGA) that has not been studied systematically thus far. A review of 149 IBD-associated cancer resections performed at our institution yielded 17 patients (11%) with 21 tumors classified as LGTGA based on the following histologic characteristics: very well-differentiated small to medium diameter glands with round or tubular profiles, low-grade cytologic characteristics and absence or paucity of desmoplastic reaction. Twelve patients had ulcerative colitis, 4 Crohn disease, and 1 indeterminate colitis. Their median age was 41.5 years (range, 28 to 58 y). Five patients had separate synchronous cancers of conventional types. LGTGAs ranged from 0.4 to 10 cm in size and varied in gross appearance. They included 5 flat lesions that were not identified visually but were detected either by palpation of the unfixed surgical specimen (1 case) or histologically in random sections (4 cases). The invasive glands usually bore a close histologic resemblance to overlying low-grade or indefinite dysplastic crypts. Twelve carcinomas (57%) with well-defined superficial regions of LGTGA progressed histologically to conventional adenocarcinoma in deeper regions. These tumors were significantly more advanced than 9 carcinomas that maintained low-grade histology throughout. Follow-up of 13 patients (76%) for a mean 4.0 years (range, 0.75 to 9.0 y) disclosed 10 (77%) with favorable outcomes and 3 (23%) with adverse outcomes. Two adverse outcomes were attributable to synchronous advanced-stage conventional cancers and the third to progression from LGTGA to poorly differentiated adenocarcinoma. The mucosa overlying and surrounding LGTGA showed low-grade dysplasia (LGD) in 18 cases (86%), indefinite dysplasia with focal LGD in 1 case (5%), and LGD with focal high-grade dysplasia (HGD) in 2 cases (10%). Immunohistochemical studies disclosed expression of MUC2 in 72%, MUC6 in 0%, CK7 in 69%, and CK20 in 100%. Coexpression of CK7 and CK20 was conserved in regions of conventional adenocarcinoma derived from LGTGA. Silencing of immunohistochemical expression of hMLH1 occurred in 6 of 11 tumors tested (55%), implicating defective DNA replication error repair in their pathogenesis. We conclude that LGTGA is a distinct clinicopathologic entity characterized by direct derivation from LGD mucosa of IBD, very well-differentiated morphology, frequent coexpression of CK7 and CK20, and frequent silencing of hMLH1. Histologic progression from LGTGA to conventional types of adenocarcinoma parallels clinical progression to more aggressive neoplasia. The potential of LGD to give rise directly to LGTGA, and by way of LGTGA to more aggressive cancers, reinforces recommendations in favor of aggressive management of IBD patients diagnosed with LGD.

Drug-induced pathology in the large intestine

Many drugs can cause pathology in the large intestine. Major classes include antibiotics, non-steroidal anti-inflammatory drugs, laxatives, anticancer drugs and immunosuppressive agents. The pathogenesis of the lesions caused by drugs is highly variable. Toxic injury and vascular insufficiency are probably the most important mechanisms. The microscopic pattern of such lesions is generally non-specific. They may produce histological patterns that resemble acute infectious-type colitis, microscopic colitis, ischaemic colitis and even chronic idiopathic inflammatory bowel disease. Specific features, such as the presence of crystals (Kayexalate), pigment and diaphragms, indicating a specific diagnosis are less common. The precise incidence of drug-induced damage to the large intestine is not known, but the importance of the phenomenon is probably underestimated. A correct histopathological diagnosis is difficult and requires a careful clinical history and the consideration of the possibility of a drug-related aetiology.

Focal myointimal hyperplasia of mesenteric veins is associated with previous trauma in surgical specimens

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood disease that occurs in the rectosigmoid colon of predominantly young, previously healthy, male patients. This disease is often confused with chronic idiopathic inflammatory bowel disease clinically, and pathologists may miss the diagnosis unless elastin stains are performed because diseased veins may readily be mistaken for arteries. The etiology of IMHMV is unclear, but a traumatic pathomechanism resulting in arterialization of the veins has been proposed. Review of bowel resection specimens ( n=68) for non-neoplastic disease within a 1-year period in patients younger than 50 years of age revealed 10 cases with focal mesenteric vein myointimal hyperplasia. Significantly more cases with focal myointimal hyperplasia of mesenteric veins (MHMV) were associated with pre-resection trauma to the involved bowel segment (5/11 vs. 5/57; p = 0.0016 ). A significant association of MHMV with pre-resection trauma supports the hypothesis that idiopathic myointimal hyperplasia of the mesenteric veins may be the result of trauma through torsion/stretching of the sigmoid colon and, subsequently, increased mesenteric venous pressure through arterialization.

Multidrug Resistance (MDR1) Gene in Inflammatory Bowel Disease: A Key Player?

The chronic idiopathic inflammatory bowel diseases (IBDs), Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by an overly aggressive cell-mediated immune response to luminal commensal bacteria in genetically susceptible individuals. 1,2 Several lines of evidence now suggest a role for the multidrug resistance (MDR1) gene and its product P-glycoprotein 170 (PgP) in the regulation of host– bacteria interaction and in the pathogenesis of IBD. PgP functions as an ATP-dependent efflux transporter pump and is highly expressed in the epithelial surfaces of intestine, biliary ductules, proximal tubules of kidneys, and central nervous system, where it forms the basis of the blood–brain barrier. 3–5 Interindividual variability of PgP expression in the intestine plays a role in the determining the pharmacokinetics of a wideranging number of substrates. 6 The exact physiological role in the gut remains unknown. The high constitutive levels of expression of PgP in the gut suggest a role in protection against xenobiotics and bacterial products. 7 This review focuses on the current data (animal studies, gene expression, and genetic studies) on the possible role of MDR1 in IBD and also future directions and implications of our current knowledge of this gene.

Pathology of chronic inflammatory bowel disease

Ulcerative colitis and Crohn's disease are the two major forms of chronic idiopathic inflammatory bowel disease. They are relapsing inflammatory conditions of the gastrointestinal tract with characteristic extra-intestinal manifestations. Accurate diagnosis depends on integration of clinical, endoscopic, radiological and histopathological features. The two conditions cannot be accurately diagnosed in some patients if only colonic disease is present; such cases are termed ‘equivocal chronic idiopathic inflammatory bowel disease’. This contribution discusses the pathology of Crohn's disease and ulcerative colitis.

Idiopathic Myointimal Hyperplasia of Mesenteric Veins

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood disease that occurs in the rectosigmoid colon of predominantly young, previously healthy male patients. IMHMV typically requires segmental resection due to complications after a relatively protracted clinical course. This disease presents a challenging diagnostic dilemma for the clinician because it is initially often confused with chronic idiopathic inflammatory bowel disease. We report a case of IMHMV, illustrate endoscopic and histopathologic features, and review key characteristics of this rare entity.

Effects of dietary fiber on inflammatory bowel disease

The chronic idiopathic inflammatory bowel diseases (IBDs), namely Crohn's disease and ulcerative colitis, appear to be derived from an inappropriate reaction towards a luminal agent, most probably driven by the intestinal microflora, which upregulates the synthesis and release of different pro-inflammatory mediators, thus contributing to tissue damage that characterizes these intestinal conditions. Several studies have reported that IBD is associated with impairment in short-chain fatty acid (SCFA) production, mainly acetate, propionate, and butyrate. They are produced in the large bowel by anaerobic bacterial fermentation of undigested dietary carbohydrates and fiber polysaccharides, with butyrate being considered as the major fuel source for colonocytes. These SCFAs have been proposed to play a key role in the maintenance of colonic homeostasis. Therefore, it is reasonable to consider therapeutic approaches that increase colonic SCFA production, as it can be achieved by administration of dietary fiber to IBD patients. Unfortunately, there is quite limited documentation of efficacy of dietary fiber in properly designed trials. This review discusses the rationale, available evidence for the use of dietary fiber and its mechanisms of action in the treatment and prevention of IBDs.

Aberrant Expression of Maspin in Idiopathic Inflammatory Bowel Disease Is Associated with Disease Activity and Neoplastic Transformation

Maspin is both overexpressed in tumors and inflammation, implicating a possible role in bridging inflammation and neoplasia. Idiopathic inflammatory bowel disease (IBD) and IBD-associated dysplasias and carcinomas represent a prototype for studying the relationship between chronic inflammatory states and neoplasia. To investigate expression of maspin in IBD and IBD-associated dysplasia and colorectal carcinoma. Immunohistochemical labeling of maspin was examined using tissue microarrays constructed from archival biopsy and resection tissue from 90 patients with 125 histologically defined lesions including 30 with inactive chronic IBD, 51 with active chronic IBD, 4 IBD-associated foci with epithelial changes indefinite for dysplasia (IFD), 7 with IBD-associated low-grade epithelial dysplasia (LGD), 8 with IBD-associated high grade epithelial dysplasia (HGD), and 25 with IBD-associated invasive colorectal adenocarcinomas. Maspin was expressed in 47/51 (92%) active chronic IBD lesions, which was significantly higher than both inactive chronic IBD (13/30, 43%) and normal mucosa (1 of 9, 11%) (p < 0.01); in particular, the diffuse pattern of maspin expression was significantly higher in active IBD (41/51, 80%), compared with inactive IBD (5/30, 17%) and normal mucosa (0%) (p < 0.01). In the multistage progression model of colitis-associated neoplasia, aberrant labeling was observed at the earliest stages, with 3/4 (75%) IFD foci, 6/7 (86%) LGD, and 8/8 (100%) HGD specimens expressing maspin, virtually always in a diffuse pattern. Expectedly, 22/25 (88%) of invasive IBD-associated cancers overexpressed maspin, including 21 with diffuse labeling. Maspin is significantly overexpressed in both active IBD and colitis-associated dysplasia compared to either inactive IBD or normal colonic mucosa, suggesting a potential role in disease "flare" as well as neoplastic progression. Targeting maspin for control of disease activity and cancer prophylaxis may be a promising novel therapeutic strategy for IBD.