Location is important: differentiation between ileal and colonic Crohn's disease.

Crohn's disease can affect any part of the gastrointestinal tract; however, current European and national guidelines worldwide do not differentiate between small-intestinal and colonic Crohn's disease for medical treatment. Data from the past decade provide evidence that ileal Crohn's disease is distinct from colonic Crohn's disease in several intestinal layers. Remarkably, colonic Crohn's disease shows an overlap with regard to disease behaviour with ulcerative colitis, underlining the fact that there is more to inflammatory bowel disease than just Crohn's disease and ulcerative colitis, and that subtypes, possibly defined by location and shared pathophysiology, are also important. This Review provides a structured overview of the differentiation between ileal and colonic Crohn's disease using data in the context of epidemiology, genetics, macroscopic differences such as creeping fat and histological findings, as well as differences in regard to the intestinal barrier including gut microbiota, mucus layer, epithelial cells and infiltrating immune cell populations. We also discuss the translation of these basic findings to the clinic, emphasizing the important role of treatment decisions. Thus, this Review provides a conceptual outlook on a new mechanism-driven classification of Crohn's disease.

2,4,6-trinitrobenzenesulfonic acid-induced colitis in Rattus norgevicus: a categorization proposal.

Reproducibility in animal research is crucial for its reliance and translational relevance. The 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced model of inflammatory bowel disease (IBD) is widely used but inconsistently and incompletely characterized throughout the literature. This hinders comparisons between studies and influences the low rate of translation of effective preclinical molecules. The purpose of this study was to categorize TNBS-induced colitis, based on macroscopic and microscopic scoring systems, and to identify basic routine parameters that could anticipate those categories. We retrospectively analysed male Wistar Rattus norvegicus (n=28 for the control group and n=87 for the TNBS group) and categorized TNBS-induced colitis in three phenotypes: Mild, Moderate and Severe colitis, as for human IBD. Also, we showed that the time course of food intake and fecal excretion (but not body weight, fluid intake or welfare scores) could foresee those categories. So, routine evaluation of food intake and fecal excretion may guide researchers in planning their experiments, selecting the animals with the severity of colitis that better matches their aims, or applying early humane endpoints to animals that will not be used in the experiments. In conclusion, categorizing TNBS-induced colitis enhances the reproducibility of data gathered with this experimental model and strengths its translational relevance.

Enteritis eosinofílica. Presentación de un caso y revisión de la literatura / Eosinophilic enteritis. Case presentation and literature review

RESUMEN La enteritis eosinofílica consiste en la presencia de infiltrados eosinofílicos en el tracto digestivo. Constituye en la actualidad una entidad rara que puede localizarse en cualquier región del tubo digestivo. Su etiopatogenia se desconoce y en muchas ocasiones se relaciona con antecedentes de atopia. Las manifestaciones clínicas varían en función de las capas afectadas. Se presentó el caso de un paciente de 26 años de edad, con antecedentes de haber sido operado de apendicitis aguda, en el año 2011. Llegó al Cuerpo de Guardia refiriendo dolor intenso, fijo; en fosa iliaca derecha, acompañado de fiebre de 39°C, con escalofríos y síntomas dispéptico. Se orientó ingreso y se le realizó una videoendoscopia, se observó gastritis antral eritematosa exudativa con test para Helicobacter pylori positivo. Además, una videolaparoscopia arrojando presencia de asas delgadas apelotonadas y adherencias no recientes en fosa iliaca derecha. A pesar del tratamiento empleado el paciente continuó con dolor y fiebre, por lo que se decidió indicarle una enteroscopia de doble balón con biopsia de íleon. Se informó que a nivel del colon presentaba una colitis crónica inespecífica y en el íleon una hiperplasia linfoide. El estudio histopatológico confirmó la colitis inespecífica y una eosinofilia moderada en íleon. Se indicó tratamiento con prednisona y mesalazina con mejoría notable del cuadro clínico, fue dado de alta con el diagnóstico de una enteritis eosinofílica, con seguimiento por consulta externa de gastroenterología. En la actualidad se mantiene asintomático (AU).

ABSTRACT Eosinophilic enteritis is the presence of eosinophilic infiltrates in the digestive tract. Currently it is a rare entity than could be located in any region of the digestive tract. Its etiopathogenesis is unknown and is related, in many cases, to antecedents of atopy, Clinical manifestations may vary according to the affected layer. The authors present the case of a patient aged 26 years, with antecedents of having undergone an acute appendicitis surgery in 2011. He arrived to Emergency referring intense, steady pain in the right iliac fossa, accompanied by a 39o C fever, chills and dyspeptic symptoms. He was admitted and a video endoscopy was carried out. An exudative erythematous antral gastritis was observed with a positive test for Helicobacter pylori. In addition, video laparoscopy also showed the presence of thin, lumped loops and no-recent adherences in the right iliac fossa. In spite of the applied treatment, the patient continued with pain and fever, so the doctors indicated a double-balloon enteroscopy with ileum biopsy. It was informed an unspecific chronic colitis at the colon level and a lymphoid hyperplasia in the ileum. The histopathologic study confirmed the unspecific colitis and a moderate eosinophilia in the ileum. A prednisone and mesalazine treatment was indicated with a notable improvement of the clinical characteristics. The patient was discharged diagnosed with a eosinophilic enteritis and follow-up in out-patient consultation of Gastroenterology. Currently he keeps on asymptomatic (AU).

Eosinophilic colitis in adults.

Eosinophilic colitis (EoC) is a pathological entity associated with abnormal infiltration of colonic mucosa by eosinophilic polynuclear cells (Eo). This is a relatively common pathology in infants and children under 2 years old, but is more rare and has been less studied in adults. EoC can be classified as primary or secondary. Primary EoC is, in the majority of cases, related to an allergic reaction, either IgE-mediated and capable of causing an anaphylactic-type food allergy, or not mediated by IgE and capable of giving rise to food enteropathy. The symptoms for adults with EoC are variable and non-specific, diarrhoea and abdominal pain being the most common signs. There is no histological consensus for the diagnosis of EoC. The presence of over 40 Eo per high-power field (×400) in at least two different colonic segments could be suggested as the criterion for the diagnosis. In adults with primary EoC, skin tests are of limited value and the response to a restrictive diet is less effective than in young children, given that IgE or non-IgE-mediated allergic reactions are rarely identified and EoC generally require medical treatment. There is no consensus on the treatment of EoC, but the potential efficacy of corticosteroids and budesonide has been demonstrated in the vast majority of cases studied.

MDCT of acute colitis in adults: an update in current imaging features.

Acute colitis is often diagnosed on multidetector row computed tomography (MDCT) because patients with this condition present with abdominal pain and a variety of nonspecific symptoms. Acute colitis has multiple causes with varying degrees of severity. Analysis of the extent of colonic involvement, presence of specific MDCT imaging features and associated signs should help radiologist narrow the diagnosis. Integrating the results of clinical examination and biological tests is mandatory, and in case of ambiguous or nonspecific MDCT findings, endoscopy and colon biopsy should always be considered for a definite diagnosis. The purpose of this review is to discuss and illustrate MDCT features that are helpful for characterizing acute colitis in adults and to provide an update in current MDCT features.

Evaluation of selected cytokine gene expression in colonic mucosa from dogs with idiopathic lymphocytic-plasmacytic colitis.

Lymphocytic-plasmacytic colitis (LPC) is a common form of inflammatory bowel disease (IBD) affecting the canine large intestine. Cytokines are thought to be involved in the pathogenesis of IBD. However, to date, few studies have investigated cytokine mRNA expression in dogs with LPC. In this study, we investigated mRNA transcription levels of T helper cell cytokines, such as IFN-γ, IL-4, IL-17 and IL-10 and pro-inflammatory cytokines, such as IL-1ß, IL-6, TNF-α, IL-8, IL-12 and IL-23, in colonic mucosa from LPC dogs by quantitative real-time RT-PCR. No significant differences were detected in cytokine mRNA expressions between dogs with LPC and controls, except for IL-23p19. Dogs with LPC failed to express a predominant cytokine profile in inflamed colonic mucosa as opposed to human IBD.

NOD2 mRNA expression and NFkappaB activation in dogs with lymphocytic plasmacytic colitis.

BACKGROUND: Nucleotide Oligomerization Domain Two (NOD2) is suggested to be an intracellular pathogen-associated molecular pattern recognition molecule. NOD2, plays a key role against bacteria by triggering a host defense response through activation of the transcription factor NFkappaB and subsequent proinflammatory cytokine production. NOD2 recently was reported to be overproduced in inflamed colonic mucosa in Crohn's disease, and to be accompanied by a significant increase in NFkappaB activity. However, few studies to date have investigated intercellular signaling molecules in dogs with lymphocytic plasmacytic colitis (LPC). HYPOTHESIS: NOD2 mRNA expression and NFkappaB activation are increased in mucosal biopsies of LPC dogs as compared with control dogs. ANIMALS: Five healthy dogs and 19 dogs with LPC. METHODS: Descending colon biopsies were obtained endoscopically. Expression of NOD2 mRNA was evaluated by semiquantitative RT-PCR in the colonic mucosa. NFkappaB binding activity was assessed by electrophoretic mobility shift assay. RESULTS: NOD2 mRNA expression was approximately 63% greater in LPC dogs than in healthy controls (P = .019). NFkappaB binding activity was approximately 45% higher in the inflamed colonic mucosa of the LPC dogs, as compared with healthy controls (P = .011). No correlations were observed among NOD2 mRNA expression levels, NFkappaB binding activity, and CIBDAI in LPC dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: NOD2 mRNA and NFkappaB activity were significantly higher in the inflamed colon of dogs with LPC, as compared with healthy controls. Our data suggest that NOD2 and NFkappaB play an important role in the pathogenesis of LPC.

Is indeterminate colitis determinable?

About 10% of patients with colitis due to inflammatory bowel disease have indeterminate colitis. Despite newer diagnostic tools, the frequency has not diminished over the past 33 years. The current preferred term among academicians is colonic inflammatory bowel disease unclassified(IBDU), although indeterminate colitis is the term endorsed for inclusion in the ICD-10 coding system. Indeterminate colitis is more frequent among children. Theanti-Saccharomyces cerevisiae (ASCA) and perinuclear anti-cytoplasmic antibody (pANCA) are useful in distinguishing IBDU from ulcerative colitis and Crohn's disease. However, current serologic and genetic studies, as well as endoscopic and imaging studies lack sufficient positive predictive values to make a definite diagnosis of Crohn's colitis or ulcerative colitis. Patients with IBDU who undergo proctocolectomy with ileal pouch-anal anastomosis have more complications than patients with ulcerative colitis. Although some patients with indeterminate colitis eventually develop characteristic ulcerative colitis or Crohn's disease, a subgroup are durably indeterminate.

Case report: grade 4 radiation-induced colitis following conventional reirradiation to a hip metastasis.

Palliative radiation therapy has been widely used for treatment of pain from metastatic bone disease. However, reirradiation is required in approximately 20% of patients initially treated with single fraction conventional palliative radiotherapy. There is a paucity of literature as to toxicities associated with reirradiation, and a lack of knowledge overall as to the cumulative dose limits for the organs at risk. We describe an uncommon late grade 4 adverse event of large bowel colitis in a patient initially radiated with 8 Gy in a single fraction, and reirradiated to the same area 3 months later with 20 Gy in 5 fractions due to pain progression.

Miscellaneous colitides.

PURPOSE OF REVIEW: A variety of diseases cause symptomatic inflammation of the colon. The epidemiology, clinical features, and/or endoscopic appearance of these conditions are distinct and histologic findings are often definitive. RECENT FINDINGS: Recent literature adds to our understanding of the epidemiology and treatment of these disorders. SUMMARY: Microscopic colitis, ischemic colitis, eosinophilic colitis, and drug-induced colitis, all cause diarrhea, often with abdominal pain, due to inflammation of the colon. Careful consideration of the clinical features and colonic mucosal biopsies usually lead to the correct diagnosis and appropriate therapy.

Absence of ABCG2-mediated mucosal detoxification in patients with active inflammatory bowel disease is due to impeded protein folding.

Xenotoxic damage in inflammatory diseases, including IBD (inflammatory bowel disease), is compounded by reduced activity of the xenobiotic transporter ABCG2 (ATP-binding-cassette G2) during the inflammatory state. An association between the activation of the unfolded protein response pathway and inflammation prompted us to investigate the possibility that reduced ABCG2 activity is causally linked to this response. To this end, we correlated expression of ABCG2 and the unfolded protein response marker GRP78 (glucose-regulated protein of 78 kDa) in colon biopsies from healthy individuals (n=9) and patients with inactive (n=67) or active (n=55) IBD, ischaemic colitis (n=10) or infectious colitis (n=14). In addition, tissue specimens throughout the small bowel from healthy individuals (n=27) and from patients with inactive (n=9) or active (n=25) Crohn's disease were co-stained for ABCG2 and GRP78. In all biopsies from patients with active inflammation, irrespective of the underlying disease, an absolute negative correlation was observed between epithelial ABCG2 expression and GRP78 expression, suggesting that inflammation-dependent activation of the unfolded protein response is responsible for suppression of ABCG2 function. The link between the unfolded protein response and functional ABCG2 expression was further corroborated by live imaging of ABCG2-expressing cells, which showed that various inflammatory mediators, including nitric oxide, activate the unfolded protein response and concomitantly reduce plasma membrane localization as well as transport function of ABCG2. Thus a novel mechanism for explaining xenobiotic stress during inflammation emerges in which intestinal inflammation activates the unfolded protein response, in turn abrogating defences against xenobiotic challenge by impairing ABCG2 expression and function.

The collagenous gastroenteritides: similarities and differences.

Collagenous gastritis, collagenous sprue, and collagenous colitis share striking histologic similarities and occur together in some patients. They also share some drug and disease associations. Pediatric cases of collagenous gastritis, however, lack most of these associations. The etiologies of the collagenous gastroenteritides are not known, so it is not clear whether they are similar because they share pathogeneses, or because they indicate a common histologic response to varying injuries. The features, disease and drug associations, and the inquiries into the pathogenesis of these disorders are reviewed.

[Colon biopsy--histological characteristics in different types of chronic colitis]. / Biopsia de colon: características histológicas en diferentes tipos de colitis crónica.

In the last few years a variety of new forms of chronic colitis have been described with defined histological characteristics. It is important both for the gastroenterologists and pathologists to be acquainted with this new clinic pathological entities. The present article is a review of the anatomo-pathological characteristics of the different types of colitis.

Automated classification of inflammation in colon histological sections based on digital microscopy and advanced image analysis.

Automated and quantitative histological analysis can improve diagnostic efficacy in colon sections. Our objective was to develop a parameter set for automated classification of aspecific colitis, ulcerative colitis, and Crohn's disease using digital slides, tissue cytometric parameters, and virtual microscopy. Routinely processed hematoxylin-and-eosin-stained histological sections from specimens that showed normal mucosa (24 cases), aspecific colitis (11 cases), ulcerative colitis (25 cases), and Crohn's disease (9 cases) diagnosed by conventional optical microscopy were scanned and digitized in high resolution (0.24 mum/pixel). Thirty-eight cytometric parameters based on morphometry were determined on cells, glands, and superficial epithelium. Fourteen tissue cytometric parameters based on ratios of tissue compartments were counted as well. Leave-one-out discriminant analysis was used for classification of the samples groups. Cellular morphometric features showed no significant differences in these benign colon alterations. However, gland related morphological differences (Gland Shape) for normal mucosa, ulcerative colitis, and aspecific colitis were found (P < 0.01). Eight of the 14 tissue cytometric related parameters showed significant differences (P < 0.01). The most discriminatory parameters were the ratio of cell number in glands and in the whole slide, biopsy/gland surface ratio. These differences resulted in 88% overall accuracy in the classification. Crohn's disease could be discriminated only in 56%. Automated virtual microscopy can be used to classify colon mucosa as normal, ulcerative colitis, and aspecific colitis with reasonable accuracy. Further developments of dedicated parameters are necessary to identify Crohn's disease on digital slides.

Clear cell colitis: a form of microscopic colitis in children.

AIM: To describe a new clinical and pathological subtype of microscopic colitis in children. METHODS: A selected group of children with abdominal pain, constipation and/or diarrhoea showing discrete or no macroscopic abnormalities on endoscopy was described. RESULTS: Multiple biopsies of colon showed large mononuclear clear cells in lamina propria of mucous membrane provided that good quality histological sections were performed and observed under a higher magnification. Otherwise, they could be misinterpreted as artefacts. Their presence in routine histology might suggest a systemic storage disease (Whipple's disease), and neuronal intestine dysplasia. Using immunohistochemical staining and electron microscopy we confirmed their origin from CD68 positive mononuclear macrophages. CONCLUSION: The presence of large clear cells is a constant microscopic feature. Failure of transient large bowel stationary macrophages plays a role in the pathogenesis of this benign microscopic clear cell colitis, sometimes coexisting with allergy.

pANCA and ASCA in the diagnosis of different subtypes of inflammatory bowel disease.

BACKGROUND/AIMS: The measurement of perinuclear antineutrophil cytoplasmic (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) has recently been suggested as a valuable and noninvasive diagnostic approach in the differentiation of ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis (IC). The aim of the study was to determine the prevalence of pANCA and ASCA in patients with inflammatory bowel disease (IBD) subgroups of different clinical course and to assess their accuracy in differential diagnosis. METHODOLOGY: The study was performed in 109 patients: 50 patients with UC, 17 with CD, 18 with IC and 24 non-IBD controls. Antibodies status has been measured with ELISA, using commercial antibody panel by MedTek kits, confirmed by IIF technique using Euroimmun panels. RESULTS: Sensitivity and specificity of pANCA+/ ASCA- pattern for UC diagnosis was 36% and 98%; pANCA-/ASCA+ for CD: 35% and 88%, pANCA/ASCA- for IC: 72% and 63%, respectively. In addition the significant positive correlation between antibodies profiles: pANCA+/ASCA- and active disease; pANCA-/ASCA+ and number of operations, as well as the negative correlation between pANCA-/ASCA- and patient's age has been found. CONCLUSIONS: Our study lends further support to the opinions that serologic assessment identifies a large subset of different subtypes of IBD patients.

Indeterminate colitis: definition, diagnosis, implications and a plea for nosological sanity.

In 1978, Price introduced the concept of indeterminate colitis to describe cases in which colonic resections had been undertaken for chronic inflammatory bowel disease (CIBD), but a definitive diagnosis of either of the classical types of CIBD, ulcerative colitis and Crohn's disease, was not possible. This was especially apposite in cases of acute fulminant disease of the colorectum. More recently, the term indeterminate colitis has been applied to biopsy material, when it has not been possible to differentiate between ulcerative colitis and Crohn's disease. In our opinion, and in those of other workers in this field, the term should be restricted to that originally suggested by Price. This then provides a relatively well-defined group of patients in whom the implications and management of the disease are becoming much clearer. Cases where there are only biopsies with CIBD, but equivocal features for ulcerative colitis and Crohn's disease, should be termed 'CIBD, unclassified', 'equivocal/non-specific CIBD' or IBD unclassified (IBDU), in line with recent recommendations. When the diagnosis is correctly restricted to colectomy specimens, there is now good evidence that the majority of cases will behave like ulcerative colitis. Furthermore, the diagnosis should not be a contraindication to subsequent pouch surgery. When the latter is undertaken, surgeons and patients can expect an increased complication rate, compared with classical ulcerative colitis, especially of pelvic sepsis, but most patients fare well. Only very occasional patients, around 10%, will eventually be shown to have Crohn's disease. This review describes the pathology of cases appropriately classified as indeterminate colitis and the implications of that diagnosis. It also highlights recent advances in its pathological features, clinical management and its immunological and genetic associations.