Search

Background and aims: Cerebrovascular accidents [CVA] have rarely been reported in inflammatory bowel disease [IBD] patients treated with anti-tumour necrosis alpha [anti-TNF alpha] agents. Our aim here was to describe the clinical course of CVA in these patients. Methods: This was a European Crohn's and Colitis Organisation [ECCO] retrospective observational study, performed as part of the CONFER [COllaborative Network For Exceptionally Rare case reports] project. A call to all ECCO members was made to report on IBD patients afflicted with CVA during treatment with anti-TNF alpha agents. Clinical data were recorded in a standardised case report form and analysed for event association with anti-TNF alpha treatment. Results: A total of 19 patients were identified from 16 centres: 14 had Crohn's disease, four ulcerative colitis and one IBD colitis unclassified [median age at diagnosis: 38.0 years, range: 18.6-62.5]. Patients received anti-TNF alpha for a median duration of 11.8 months [range: 0-62] at CVA onset; seven had previously been treated with at least one other anti-TNF alpha agent. Complete neurological recovery was observed in 16 patients. Anti-TNF alpha was discontinued in 16/19 patients. However, recurrent CVA or neurological deterioration was not observed in any of the 11 patients who received anti-TNF alpha after CVA [eight resumed after temporary cessation, three continued without interruption] for a median follow-up of 39.8 months [range: 5.6-98.2]. Conclusion: These preliminary findings do not unequivocally indicate a causal role of anti-TNF alpha in CVA complicating IBD. Resuming or continuing anti-TNF alpha in IBD patients with CVA may be feasible and safe in selected cases, but careful weighing of IBD activity versus neurological status is prudent. [ABSTRACT FROM AUTHOR]

Oral antigen uptake can induce systemic immune responses ranging from tolerance to immunity. However, the underlying mechanisms are poorly understood, especially in humans. Here, keyhole limpet hemocyanin (KLH), a neoantigen which has been used in earlier studies of oral tolerance, was fed in a repeated low-dose and a single high-dose protocol to healthy volunteers. KLH-specific CD4 [ABSTRACT FROM AUTHOR]

T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3. Here we show that CD4+ cells from T-bet-/- mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4-blockade of IL-4 receptor (R) signaling. In addition, under these conditions, Th1 cells from T-bet-/- mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity. In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet-/- cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed. Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels. These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rβ2 chain unless GATA-3 levels or function is regulated by T-bet. Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene. [ABSTRACT FROM AUTHOR]

Background/Aims: We report the case of a 53-year-old man with fever and severe abdominal pain following an upper respiratory tract infection. Methods/Results: The clinical signs, the laboratory markers, and the ultrasound findings were consistent with acute acalculous cholecystitis and he underwent cholecystectomy. Histologically the gallbladder showed vasculitis and the patient developed postoperatively a purpuric rash of the legs with transient ankle arthritis. Gastroscopy revealed prepyloric ulcers consistent with vasculitis. The patient was diagnosed as having Henoch-Schönlein purpura. Gastric ulcers as well as arthritis disappeared upon treatment with corticosteroids and proton pump inhibitors. Conclusion: Taken together, Henoch-Schönlein purpura can mimic acute cholecystitis and should be considered as a rare differential diagnosis of acute cholecystitis. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The Th1 and Th2 T cell responses that underlie inflammatory bowel diseases (IBDs) are likely to depend on NF-kappaB transcriptional activity. We explored this possibility in studies in which we determined the capacity of NF-kappaB decoy oligodeoxynucleotides (decoy ODNs) to treat various murine models of IBD. In initial studies, we showed that i.r. (intrarectal) or i.p. administration of decoy ODNs encapsulated in a viral envelope prevented and treated a model of acute trinitrobenzene sulfonic acid-induced (TNBS-induced) colitis, as assessed by clinical course and effect on Th1 cytokine production. In further studies, we showed that NF-kappaB decoy ODNs were also an effective treatment of a model of chronic TNBS-colitis, inhibiting both the production of IL-23/IL-17 and the development of fibrosis that characterizes this model. Treatment of TNBS-induced inflammation by i.r. administration of NF-kappaB decoy ODNs did not inhibit NF-kappaB in extraintestinal organs and resulted in CD4+ T cell apoptosis, suggesting that such treatment is highly focused and durable. Finally, we showed that NF-kappaB decoy ODNs also prevented and treated oxazolone-colitis and thus affect a Th2-mediated inflammatory process. In each case, decoy administration led to inflammation-clearing effects, suggesting a therapeutic potency applicable to human IBD. [ABSTRACT FROM AUTHOR]

Background: The patient perspective is essential for assessing disease severity, but it is not always adequately considered. We describe how a comprehensive clinical disease severity index (DSI) for inflammatory bowel disease (IBD) correlates with patient global self-assessment (PGSA)., Methods: In an individually linked parallel online survey, physicians provided the DSI, and patients provided self-assessed severity using a global question and visual analog scale (0-100) (PGSA). Mean DSI values by PGSA were calculated with 95% confidence intervals. Pearson correlation (r) and the intraclass correlation coefficient were calculated for PGSA vs DSI. Positive predictive values for identifying severe disease with PGSA categories as a reference were based on a threshold >22 points., Results: The primary analysis included 89 pairs (46 Crohn's disease [CD], 43 ulcerative colitis [UC]) with strict criteria and 147 pairs when less stringent. Common reasons for exclusion were missing values for albumin or colonoscopy. Mean DSI values showed no clear trend with increasing PGSA in CD but good discrimination between moderate, severe, and very severe PGSA in UC. For PGSA on the visual analog scale, r was 0.54 for CD and 0.59 for UC (difference in means: CD 27.7, UC 13.8; intraclass correlation coefficient: CD 0.48, UC 0.58). A high DSI predicted severe disease in 76.2% of CD and 65.2% of UC., Conclusions: The DSI showed good discrimination for patient-reported disease severity in UC but performed unsatisfactorily in CD. Correlations were moderate. Further refinement of the DSI is suggested to better reflect the patient perspective., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Die Interessenerklärungen sind im Anhang dargestellt.

Background: Ustekinumab (CNTO 1275) and briakinumab (ABT-874) are monoclonal antibodies that target the standard p40 subunit of the cytokines interleukin-12 and interleukin-23 (IL-12/23p40), which are involved in the pathogenesis of Crohn's disease., Objectives: The objectives of this review were to assess the efficacy and safety of anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease., Search Methods: The following databases were searched from inception to September 16, 2014: PubMed, MEDLINE, EMBASE, and the Cochrane Library (CENTRAL). References and conference abstracts were searched to identify additional studies., Selection Criteria: Randomized controlled trials (RCTs) trials in which monoclonal antibodies against IL-12/23p40 were compared to placebo or another active comparator in patients with active Crohn's disease were included. , Data Collection and Analysis: Two authors independently screened  studies for inclusion and extracted data. Methodological quality was assessed using the Cochrane risk of bias tool. The primary outcome was failure to induce clinical remission, defined as a Crohn's disease activity index (CDAI) of < 150 points. Secondary outcomes included failure to induce clinical improvement, serious adverse events, and withdrawals due to adverse events. Clinical improvement was defined as decreases of > 70 or > 100 points in the CDAI from baseline. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for each outcome. A fixed-effect model was used to pool data. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria., Main Results: Four randomized controlled trials (n = 955 patients) met the inclusion criteria. A low risk of bias was assigned to all studies. The two briakinumab trials were not pooled due to differences in doses and time points for analysis. In both studies there was no statistically significant difference in remission rates. One study (n = 79) compared doses of 1 mg/kg and 3 mg/kg to placebo. In the briakinumab group 70% (44/63) of patients failed to enter clinical remission at 6 or 9 weeks compared to 81% (13/16) of placebo patients (RR 0.86, 95% CI 0.65 to 1.14). Subgroup analysis revealed no significant differences by dose. The other briakinumab study (n = 230) compared intravenous doses of 200 mg, 400 mg and 700 mg with placebo. Eighty-four per cent (154/184) of briakinumab patients failed to enter clinical remission at six weeks compared to 91% (42/46) of placebo patients (RR 0.92, 95% CI 0.83 to 1.03). Subgroup analysis revealed no significant differences by dose. GRADE analyses of the briakinumab studies rated the overall quality of the evidence for the outcome clinical remission as low due. Based on the results of these two studies the manufacturers of briakinumab stopped production of this medication. The two ustekinumab studies (630 patients) were pooled despite differences in intravenous doses (i.e. 1mg/kg, 3 mg/kg, 4.5 mg/kg, and 6 mg/kg), however the subcutaneous dose group was not included in the analysis, as it was unclear if subcutaneous was equivalent to intravenous dosing. There was no statistically significant difference in remission rates. At week six, 85% (356/420) of ustekinumab patients failed to enter remission compared to 89% (142/159) of placebo patients (RR 0.94, 95% CI 0.88 to 1.01). Subgroup analysis showed no statistically significant difference by dose. There were statistically significant differences in clinical improvement between ustekinumab and placebo-treated patients. In the ustekinumab group, 55% (230/420) of patients failed to improve clinically (i.e. 70-point decline in CDAI score), compared to 72% (115/159) of placebo patients (RR 0.75, 95% CI 0.66 to 0.86). Subgroup analysis revealed significant differences compared to placebo for the 1 mg/kg, 4.5 mg/kg and 6 mg/kg dosage subgroups. Similarly for a 100-point decline in CDAI, 62% (262/420) of patients in the ustekinumab group failed to improve clinically compared to 78% (124/159) of placebo patients (RR 0.79, 95% CI 0.71 to 0.89). Subgroup analysis showed a significant difference compared to placebo for the 4.5 mg/kg dose group. GRADE analyses of the ustekinumab studies rated the overall quality of the evidence for the outcomes clinical remission and clinical response as moderate. There were no statistically significant differences in the incidence of adverse events, serious adverse events or withdrawal due to adverse events. Sixty-seven per cent (316/473) of ustekinumab patients developed at least one adverse event compared to 73% (135/184) of placebo patients (RR 0.92, 95% CI 0.83 to 1.03). A GRADE analysis indicated that the overall quality of the evidence for this outcome was high. Six per cent (29/473) of ustekinumab patients had a serious adverse event compared to 8% (14/184) of placebo patients (RR 0.81, 95% CI 0.44 to 1.49). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low. The most common adverse events in briakinumab patients were injection site reactions and infections. Infections were the most common adverse event in ustekinumab patients. Worsening of Crohn's disease and serious infections were the most common serious adverse events., Authors' Conclusions: Although we are uncertain about the efficacy of ustekinumab for induction of remission, moderate quality evidence suggests that ustekinumab may be effective for induction of clinical improvement in patients with moderate to severe CD. Due to small numbers of patients in dose subgroups the optimal dosage of ustekinumab is unclear. Briakinumab and ustekinumab appear to be safe. Due to sparse data we were unable to determine the risk of serious adverse events. Further studies are required to determine the efficacy and safety of ustekinumab in patients with moderate to severe CD. The results of three phase III trials that are currently underway will provide important new information.

Aim: To detect high risk patients with a progressive disease course of ulcerative colitis (UC) requiring immunosuppressive therapy (IT)., Methods: A retrospective, multicenter analysis of 262 UC patients from eight German tertiary inflammatory bowel disease centres was performed. Patients were divided into two groups depending on the patients need to initiate immunosuppressive therapy in the disease course. A comparison between the two groups was made with regard to demographics, clinical and laboratory parameters obtained within three months after UC diagnosis and the response to first medical therapy. Using this data, a prognostic model was established to predict the individual patients probability of requiring an immunosuppressive therapy., Results: In 104 (39.7%) out of 262 patients, UC therapy required an immunosuppressive treatment. Patients in this group were significantly younger at time of diagnosis (HR = 0.981 ± 0.014 per year, P = 0.009), and required significantly more often a hospitalisation (HR = 2.5 ± 1.0, P < 0.001) and a systemic corticosteroid therapy at disease onset (HR = 2.4 ± 0.8, P < 0.001), respectively. Response to steroid treatment was significantly different between the two groups of patients (HR = 5.2 ± 3.9 to 50.8 ± 35.6 compared to no steroids, P = 0.016 to P < 0.001). Furthermore, in the IT group an extended disease (HR = 3.5 ± 2.4 to 6.1 ± 4.0 compared to proctitis, P = 0.007 to P = 0.001), anemia (HR = 2.2 ± 0.8, P < 0.001), thrombocytosis (HR = 1.9 ± 1.8, P = 0.009), elevated C-reactive protein (CRP) (HR = 2.1 ± 0.9, P < 0.001), and extraintestinal manifestations in the course of disease (HR = 2.6 ± 1.1, P = 0.004) were observed. Six simple clinical items were used to establish a prognostic model to predict the individual risk requiring an IT. This probability ranges from less than 2% up to 100% after 5 years. Using this, the necessity of an immunosuppressive therapy can be predicted in 60% of patients. Our model can determine the need for an immunosuppressive drug therapy or if a "watch and wait" approach is reasonable already early in the treatment course of UC., Conclusion: Using six simple clinical parameters, we can estimate the patients individual risk of developing a progressive disease course.

Background: The effect of psychological interventions in inflammatory bowel diseases (IBD) is controversial., Objectives: To assess the effects of psychological interventions (psychotherapy, patient education, relaxation techniques) on health related quality of life, coping, emotional state and disease activity in IBD., Search Strategy: We searched the specialized register of the IBD/FBD Group, CENTRAL (Issue 5, 2010) and from inception to April 2010: Medline, Embase, LILACS, Psyndex, CINAHL, PsyInfo, CCMed, SOMED and Social SciSearch. Conference abstracts and reference lists were also checked., Selection Criteria: Randomized, quasi-randomized and non randomized controlled trials of psychological interventions in children or adults with IBD with a minimum follow up time of 2 months., Data Collection and Analysis: Data were extracted and study quality was independently assessed by two raters. Pooled standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated using a random effects model., Main Results: Twenty-one studies were eligible for inclusion (1745 participants, 8 RCT, 4 QRCT, 8 NRCT; 19 in adults, 2 in adolescents). Most studies used multimodular approaches. The risk of bias was high for all studies.In adults, psychotherapy had no effect on quality of life at around 12 months (3 studies, 235 patients, SMD -0.07; 95% CI -0.33 to 0.19), emotional status (depression, 4 studies, 266 patients, SMD 0.03; 95% CI -0.22 to 0.27) or proportion of patients not in remission (5 studies, 287 patients, OR 0.85; 95% CI 0.48 to 1.48). Results were similar at 3 to 8 months. There was no evidence for statistical heterogeneity or subgroup effects based on type of disease or intensity of the therapy. In adolescents, there were positive short term effects of psychotherapy on most outcomes assessed including quality of life (2 studies, 71 patients, SMD 0.70; 95% CI 0.21 to 1.18) and depression (1 study, 41 patients, SMD -0.62; 95% CI -1.25 to 0.01).Educational interventions were ineffective with respect to quality of life at 12 months (5 studies, 947 patients, SMD 0.11; 95% CI -0.02 to 0.24), depression (3 studies, 378 patients, SMD -0.08; 95% CI -0.29 to 0.12) and proportion of patients not in remission (3 studies, 434 patients, OR 1.00; 95% CI 0.65 to 1.53)., Authors' Conclusions: There is no evidence for efficacy of psychological therapy in adult patients with IBD in general. In adolescents, psychological interventions may be beneficial, but the evidence is limited. Further evidence is needed to assess the efficacy of these therapies in subgroups identified as being in need of psychological interventions, and to identify what type of therapy maybe most useful.

The German clinical practice guideline on diagnosis and therapy of Crohn's disease is the result of an evidence-based consensus conference under the auspices of the German Gastroenterologic Society and the Competence Network IBD. This article will summarize the recommendations most important for the general practitioner.Crohn's disease is diagnosed in cooperation with a gastroenterologist who is performing endoscopy and possibly ultrasound. Uncomplicated relapses can nevertheless be successfully treated at the office of a family physician - mostly with steroids. Steroids are not appropriate for long-term treatment though. In those cases an early treatment with immunosuppressants in collaboration with a gastroenterologist is required. Cooperation with several different sub specialists is necessary when surgery is required as well as for the treatment of fistula, psychosomatic aspects and extraintestinal manifestations.

Background: Erythrodermic psoriasis is a severe manifestation of psoriasis and can be triggered by several factors., Case Report: A 35-year-old man was admitted with severe, almost generalized exfoliative, oozing erythrodermic psoriasis, fever, and cramping of hands and legs. He was under systemic treatment with acitretin. Laboratory examination revealed a marked hypocalcemia as a consequence of primary hypopara thyroidism as well as hypalbuminemia. After normalization of the serum calcium and albumin levels, cutaneous symptoms and fever rapidly improved. No infectious etiology could be found. Hypoparathyroidism together with a right-sided aorta was caused by a 22q11 deletion syndrome., Conclusion: Epidermal cell proliferation and formation of intercellular junctional components of the epidermis are strongly calcium-dependent. Furthermore, carriers like albumin are necessary for the transportation of acitretin in the peripheral tissue. This case report suggests that calcium can be involved in psoriasis pathogenesis at least in a subgroup of patients and that systemic retinoids exhibit insufficient effectiveness under low serum albumin levels.