CD-related Complications Research Articles

Clinical outcome of Crohn??s disease according to the Vienna classification: disease location is a useful predictor of disease course

Crohn's disease (CD) is a complex genetic disease with multiple clinical patterns. Clinical classifications may help to identify subgroups of patients that have a distinct pattern of disease, and they are also a prerequisite for the conduction of genetic and therapeutic studies. The aim of this study was to determine the usefulness of the Vienna classification in patient care and clinical studies. The clinical data of patients were carefully reviewed retrospectively. The behaviour and location of the disease were determined according to the Vienna classification and additional clinical characteristics including surgical data, vitamin B12 status and medication were also assessed. Data according to the Vienna classification of 292 CD cases were available. The mean age at diagnosis was 31.4 years. The operation rate was higher in patients with ileocolonic localization (P<0.05) and stricturing and penetrating disease behaviour (P<0.001). The incidence of vitamin B12 deficiency was 41.9% in cases with ileal involvement and 20.7% in cases with disease confined to the colon. In 187 cases (64.0%) an operation was performed because of CD-related complications, in a majority (126, 67.4%) this took place within 5 years after diagnosis. Intolerance of azathioprine occurred in 36 cases (22.0%). Ileocolonic disease localization is associated with a complicated course of disease. Vitamin B12 deficiency occurs frequently, also in patients with disease apparently confined to the colon. We propose that location parameters can be used for the prediction of disease course in clinical settings and in interventional studies.

Splenic Hypofunction and the Spectrum of Autoimmune and Malignant Complications in Celiac Disease

We investigated the prevalence of functional hyposplenism in autoimmune disorder (AID)-associated and complicated celiac disease (CD). In addition, because the association between hyposplenism and overwhelming infections caused by Streptococcus pneumoniae in patients with CD is well known, we investigated whether immunoglobulin (Ig)M memory B cells, which are responsible for protection against infections by encapsulated bacteria and require the spleen for their generation and/or survival, mirror the reduced splenic function in CD. Peripheral blood samples were collected from 73 adult CD patients (27 with AID, 36 without AID, and 10 with CD-related complications including enteropathy-associated T-cell lymphoma, refractory sprue, and ulcerative jejunoileitis). Thirty-four non-CD patients with AID, 35 healthy volunteers, and 29 splenectomized patients also were studied. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function, and flow cytometry was performed to analyze peripheral blood B cells. A significantly higher risk for hyposplenism was found in AID-associated CD (59%) and complicated CD (80%) than in uncomplicated CD without AID (19%). In AID-associated CD, the degree of splenic function did not correlate to the duration of gluten-free diet. In AID-associated and complicated CD, the frequency of circulating IgM memory B cells was significantly lower than in CD patients without AID or healthy subjects. A significant inverse correlation between IgM memory B cells and pitted red cells was found in all 73 CD patients. The prevalence of splenic hypofunction is increased in CD with AID and in complicated CD, and is not related to the duration of gluten-free diet. IgM memory B cells are reduced in AID-associated and complicated CD. This defect, which is related to the impairment of splenic function, might predispose hyposplenic CD patients to infections by encapsulated bacteria.

Capsule Endoscopy (CE) in Evaluation of Patients with Celiac Disease (CD)

Aim: To establish the accuracy of CE in diagnosing villous atrophy (VA) using small bowel (SB) histology as a “gold standard”. To evaluate the ability of CE to correctly interpret mucosal changes in CD patients after introduction of a gluten free diet (GFD). Methods: Participants (CD and control group) had serology, upper endoscopy, SB biopsy and CE. Standard endoscopic criteria in identifying VA were applied to CE. An investigator blinded to other tests' findings randomly reviewed CE images. Patients' identification details were coded. Histological confirmation of CD (Marsh's III-IV type) was considered diagnostic of CD. All tests were repeated in CD group to assess patients' response after 6 months of the GFD. A dedicated dietitian assessed patients' baseline gluten intake followed by compliance to the GFD. The investigator blinded to other tests' findings reviewed and compared CE images taken before with the images taken after introduction of the GFD. Results: Evaluated 41 (29 CD, 12 healthy controls). Mean age-45.3 yr, SD=15.94 (range 17-77). 1 patient's data (CD group) was excluded from the analysis (Marsh's I-II type). In the diagnosis of VA, CE yielded a sensitivity/a specificity of 89.3%/91.7%, positive/negative predictive values of 96.2%/78.6%. Importantly, CE revealed 3 CD patients with ulcerative jejunitis. 15 CD patients were re-evaluated after 6 months of the GFD. 12/15 improved histologically and clinically. 3/15 did not experience any changes in their condition. 1 of the 3 was found completely and 1 partially non-complaint to the GFD. When compared to histology CE correctly interpreted positive/negative mucosal changes after introduction of the GFD in 12/15 patients (80%). Conclusions: CE may be suggested for further work up of histologically confirmed CD patients. With its ability to visualize the entire SB and high accuracy in identifying VA, CE could provide a non-invasive way of evaluating CD patients, monitoring the response to the GFD as well as lifelong screening for CD related complications such as ulcerative jejunitis or malignancy.

Management of Crohn's disease of the ileoanal pouch with infliximab.

The occurrence of Crohn's disease (CD) in a patient with an ileal-pouch anastomosis (IPAA) often results in severe morbidity and significant chance of reservoir loss. We report our experience of the use of infliximab in these patients. Medical records of 26 patients with an IPAA and CD-related complications were reviewed. The median time between the IPAA and the diagnosis of CD was 4.5 yr (range 0.1-16 yr). The main reasons for changing the original ulcerative colitis diagnosis to CD were complex perianal or pouch fistulizing disease in 14 patients (54%), prepouch ileitis in five (19%), and both prepouch ileitis and complex fistula in seven (27%). Patients received one to three doses of infliximab over 8 wk as induction therapy. Subsequently the patients received a variable number of maintenance infusions. At a short term follow-up, 16/26 patients (62%) had a complete response, six of 26 (23%) had a partial response, and four of 26 (15%) had no response. Information regarding long term follow-up was available in 24 patients. After a median follow-up of 21.5 months (range 3-44 months), eight patients (33%) either had their pouch resected or had a persistent diverting ileostomy. The pouch was functional in 16/24 (67%) patients, with either good (n = 7) or acceptable (n = 7) clinical results in 14/24 (58%). Of those 14 patients, 11 were under long term, on demand, or systematic maintenance treatment with infliximab. Infliximab is beneficial in both the short and long term treatment of patients with an IPAA performed for a presumed diagnosis of ulcerative colitis who subsequently develop CD-related complications. Good pouch function requires long term treatment with infliximab in most patients.

Management of Crohn's disease of the ileoanal pouch with infliximab

Objectives The occurrence of Crohn's disease (CD) in a patient with an ileal-pouch anstomosis (IPAA) often results in severe morbidity and significant chance of reservoir loss. We report our experience of the use of infliximab in these patients. Methods Medical records of 26 patients with an IPAA and CD-related complications were reviewed. The median time between the IPAA and the diagnosis of CD was 4.5 yr (range 0.1–16 yr). The main reasons for changing the original ulcerative colitis diagnosis to CD were complex perianal or pouch fistulizing disease in 14 patients (54%), prepouch ileitis in five (19%), and both prepouch ileitis and complex fistula in seven (27%). Patients received one to three doses of infliximab over 8 wk as induction therapy. Subsequently the patients received a variable number of maintenance infusions. Results At a short term follow-up, 16/26 patients (62%) had a complete response, six of 26 (23%) had a partial response, and four of 26 (15%) had no response. Information regarding long term follow-up was available in 24 patients. After a median follow-up of 21.5 months (range 3–44 months), eight patients (33%) either had their pouch resected or had a persistent diverting ileostomy. The pouch was functional in 16/24 (67%) patients, with either good (n = 7) or acceptable (n = 7) clinical results in 14/24 (58%). Of those 14 patients, 11 were under long term, on demand, or systematic maintenance treatment with infliximab. Conclusions Infliximab is beneficial in both the short and long term treatment of patients with an IPAA performed for a presumed diagnosis of ulcerative colitis who subsequently develop CD-related complications. Good pouch function requires long term treatment with infliximab in most patients.

Transforming growth factor-betas and their signaling receptors are coexpressed in Crohn's disease.

To evaluate mechanisms that contribute to tissue repair and tissue remodeling in Crohn's disease (CD). Transforming growth factor-betas (TGF-betas) are involved in different chronic inflammatory disorders. They function by binding to two receptors, type I (TbetaR-I) subtype ALK5 and type II (TbetaR-II), which are concomitantly required for signal transduction. Tissues were obtained from 18 patients with CD (10 female patients, 8 male patients, median age 38.7 years [range 16 to 58 years]) undergoing surgery because of CD-related complications. Tissue samples of 18 healthy organ donors (10 female subjects, 8 male subjects, median age 50.3 years [range 15 to 65 years]) served as controls. The expression and localization of TGF-beta1, TGF-beta2, TGF-beta3, TbetaR-IALK5, TbetaR-II, and TbetaR-III were studied by Northern blot analysis, in situ hybridization, and immunohistochemistry. On Northern blot analysis, 94% of the CD samples exhibited enhanced TGF-beta1, TGF-beta3, and TbetaR-II mRNA expression compared with controls. TGF-beta2 was increased in 72%, TbetaR-IALK5 in 72%, and TbetaR-III in 82% of the patients with CD. On in situ hybridization and immunohistochemical analysis, TGF-beta1, TbetaR-IALK5, and TbetaR-II were seen to be colocalized in the lamina propria cells and in the lymphocytes closest to the luminal surface, but also in the remaining epithelial cells, and in fibroblasts of CD tissue samples. The concomitant overexpression of TGF-betas and their signaling receptors in CD points to a potential role of these regulatory molecules in the pathophysiology of CD. Activation of TGF-beta-mediated pathways might promote the repair of mucosal injury by enhancing the process of reepithelization, but might also contribute to extracellular matrix generation and subsequently to intramural fibrosis and intestinal obstruction.