Acetarsol in the management of mesalazine refractory ulcerative proctitis: a tertiary-level care experience

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Background Mesalazine-refractory ulcerative proctitis is common, with a significant proportion of the patients requiring escalation to immunomodulators or biological therapy. Three small preliminary cohort studies suggested good clinical efficacy for the organic arsenic derivative acetarsol in the management of proctitis. Our aim was to describe our experience on the use of acetarsol in proctitis and to review all existing evidence on its safety and efficacy.Patients and methodsWe retrospectively reviewed clinical records of all ulcerative colitis patients exposed to acetarsol at Nottingham University Hospitals since 2012. Clinical response was determined basing on physicians' global assessments and patients' improvement over the baseline (reduction in stool frequency and rectal bleeding). Clinical remission was defined as total resolution of symptoms including bleeding cessation. Serum arsenic, C-reactive protein and faecal calprotectin levels reviewed when available. Nonparametric analysis performed.ResultsTwenty-eight (16 males) patients with median (range) age 39 (35) and 9 (19) years disease duration received acetarsol suppositories for proctitis. All had failed mesalazine or corticosteroid topical therapy, with 50% having additionally failed immunomodulators. Median treatment duration was 70 (64) days. 16/28 were prescribed acetarsol more than once. 67.9% achieved clinical response and 46.4% clinical remission. 32.1% required treatment escalation to steroids, thiopurines or antitumour necrosis factor agents. 6/28 patients stopped acetarsol due to side effects.ConclusionAcetarsol could be an effective and safe option in the management of refractory proctitis. A definitive trial with long-term safety follow-up is required to investigate the efficacy and safety of this promising drug

Evolution of treatment targets in Crohn’s disease

Crohn’s disease is a chronic relapsing and remitting inflammatory disorder of the gastrointestinal tract, associated with significantly morbidity due to both symptoms and complications that have a considerable detrimental impact on a patient’s quality of life. An early treat to target approach with disease modifying agents has been shown to significantly improve long term outcomes, demonstrated by a number of therapeutic targets in a number of modalities. This review will outline the current treatment targets and measures of disease burden in Crohn’s disease

Physical activity and fatigue in adults with Inflammatory Bowel Disease (IBD): a systematic review

Background: Fatigue is frequently reported in inflammatory bowel disease (IBD). IBD has been shown to have an impact on, and be impacted by, physical activity levels in IBD patients, Yet, to date, there have been no systematic reviews considering the impact of physical activity on levels of IBD fatigue.Aim: This aim of this review is to explore the current body of knowledge of what kind of physical activity interventions are available to treat IBD fatigue.Methods: Systematic database searchs (CINAHL, EMBASE, PsychInfo, PsycARTICLES, AMED, Medline) and hand searching were conducted on 03/03/2019. Searches were restricted to ‘human’, ‘adult’, ‘primary research’ and ‘English language’publications. No time limit was set. Quality appraisal and data extraction was undertaken by at least 2 reviewers.Results: searches yielded 32 publications; 2 studies were included in the review. Physical activity is inhibited by higher fatigue levels, lowering HRQoL, but also as a means of reducing fatigue, subsequently improving HRQoL.Conclusion: There was very little data eligible for inclusion in this review, and it was not of a high quality. The findings of the review suggest that physical activity may be beneficial for IBD fatigue, but this cannot be definitively stated. Evidence suggests physical activity is safe to undertake in active disease, therefore better-quality studiesare needed in this area

The pattern of underlying cause of death in patients with inflammatory bowel disease in England: a record linkage study

Background and Aims: Numerous studies have established that mortality risk in IBD patients is higher than the general population, but the causes of death have seldom been examined. We aimed to describe causes of death in IBD. Methods: A matched cohort study using UK general practice data from Clinical Practice Research Datalink linked to death registration records. We described the distribution of causes of death among IBD patients by age at death and time since IBD diagnosis. We estimated age-specific mortality rates and hazard ratios of death in multivariable Cox proportional hazards models. Results: 20,293 IBD patients were matched to 83,261 non-IBD patients. The mortality rate was 40% higher in IBD patients (2005 deaths) than in non-IBD patients (6024 deaths) (adjusted overall hazard ratio = 1.4, 95% CI = 1.4—1.5), with greater risk of death in Crohn’s disease (hazard ratio = 1.6, 1.5—1.7) than in ulcerative colitis (1.3, 1.3—1.4). Causes attributable to IBD constituted 3.7% of all deaths in ulcerative colitis and 8.3% in Crohn’s disease. Among IBD patients, death was less likely to be due to circulatory, respiratory or neoplastic diseases than non-IBD patients. In both IBD and non-IBD patients all these causes became more clinically important with advancing age, with the commonest neoplastic cause of death being lung cancer, rather than gastrointestinal cancers. Conclusion: IBD patients have an additional risk of death. Most IBD patients die of circulatory or respiratory causes, and the contribution to mortality from long-term complications of IBD are clinically less important

Magnetic resonance imaging biomarkers of gastrointestinal motor function and fluid distribution

Magnetic resonance imaging (MRI) is a well established technique that has revolutionized diagnostic radiology. Until recently, the impact that MRI has had in the assessment of gastrointestinal motor function and bowel fluid distribution in health and in disease has been more limited, despite the novel insights that MRI can provide along the entire gastrointestinal tract. MRI biomarkers include intestinal motility indices, small bowel water content and whole gut transit time. The present review discusses new developments and applications of MRI in the upper gastrointestinal tract, the small bowel and the colon reported in the literature in the last 5 years

Orbital inflammatory complications of Crohn’s disease: a rare case series

Orbital inflammatory disease is a rare ophthalmic manifestation of Crohn’s disease. Inflammation is characteristically non-specific, involving one or multiple structures of the orbit. Mechanisms of disease and optimal methods of treatment are poorly understood. The aim of this report is to present three cases of orbital involvement in Crohn’s disease. A retrospective case note review of patients with orbital inflammatory disease and Crohn’s disease was performed at our academic centre to determine the clinical, imaging and histopathological features of this condition and its relationship to intestinal Crohn’s disease. Three patients were identified with orbital inflammatory manifestations complicating Crohn’s disease. All patients described were female with active intestinal disease and had a history of treatment with immunosuppressive therapies. Similarities were observed in clinical presentations with variance noted in radiological and histopathological findings. In all cases, symptoms improved with oral corticosteroids or non-steroidal drugs in combination with anti-tumour necrosis factor (anti-TNF) agents. Inflammatory bowel disease-related orbital complications are rare but potentially vision-threatening. It is important to consider mimics of orbital inflammatory disease such as systemic inflammatory disease, malignancy, congenital malformations, infection and trauma when formulating a comprehensive differential diagnosis. Therapeutic intervention is directed towards preservation of vision and orbital function and reducing the acute inflammatory process. Corticosteroids are typically the initial treatment of choice for moderate-to-severe disease, although several classes of immunomodulatory agents have been variably useful in treating this condition. Heightened awareness and close cooperation between gastroenterologists and ophthalmologists is mandatory

Acetarsol Suppositories: Effective Treatment for Refractory Proctitis in a Cohort of Patients with Inflammatory Bowel Disease.

BACKGROUND: Management of proctitis refractory to conventional therapies presents a common clinical problem. The use of acetarsol suppositories, which are derived from organic arsenic, was first described in 1965. Data concerning clinical efficacy and tolerability are very limited. AIM: To examine the efficacy of acetarsol suppositories for the treatment of refractory proctitis. METHODS: A retrospective analysis was performed on patients with inflammatory bowel disease treated with acetarsol suppositories between 2008 and 2014 at Addenbrooke's Hospital, Cambridge, United Kingdom. Clinical response was defined as resolution of symptoms back to baseline at the time of next clinic review. RESULTS: Thirty-nine patients were prescribed acetarsol suppositories between March 2008 and July 2014 (29 patients with ulcerative colitis, nine with Crohn's disease, and one with indeterminate colitis). Thirty-eight were included for analysis. The standard dose of acetarsol was 250 mg twice daily per rectum for 4 weeks. Clinical response was observed in 26 patients (68%). Of the 11 patients who had endoscopic assessment before and after treatment, nine (82%) showed endoscopic improvement and five (45%) were in complete remission (Wilcoxon signed-rank test p = 0.006). One patient developed a macular skin rash 1 week after commencing acetarsol, which resolved within 4 weeks of drug cessation. CONCLUSION: Acetarsol was effective for two out of every three patients with refractory proctitis. This cohort had failed a broad range of topical and systemic treatments, including anti-TNFα therapy. Clinical efficacy was reflected in significant endoscopic improvement. Adverse effects of acetarsol were rare

Delphi consensus survey: the opinions of patients living with refractory ulcerative proctitis and the health care professionals who care for them

© 2023 The Authors. Published by BMJ Publishing Group. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.1136/bmjgast-2023-001139Background Refractory ulcerative proctitis presents a huge clinical challenge not only for the patients living with this chronic, progressive condition but also for the professionals who care for them. Currently, there is limited research and evidence-based guidance, resulting in many patients living with the symptomatic burden of disease and reduced quality of life. The aim of this study was to establish a consensus on the thoughts and opinions related to refractory proctitis disease burden and best practice for management. Methods A three-round Delphi consensus survey was conducted among patients living with refractory proctitis and the healthcare experts with knowledge on this disease from the UK. A brainstorming stage involving a focus group where the participants came up with an initial list of statements was completed. Following this, there were three rounds of Delphi surveys in which the participants were asked to rank the importance of the statements and provide any additional comments or clarifications. Calculation of mean scores, analysis of comments and revisions were performed to produce a final list of statements. Results In total, 14 statements were suggested by the focus group at the initial brainstorming stage. Following completion of three Delphi survey rounds, all 14 statements reached consensus following appropriate revision. Conclusions We established consensus on the thoughts and opinions related to refractory proctitis from both the experts who manage this disease and the patients living with it. This represents the first step towards developing clinical research data and ultimately the evidence needed for best practice management guidance of this condition.Published versio

Skeletal muscle anabolic and insulin sensitivity responses to a mixed meal in adult patients with active Crohn's disease

© 2020 European Society for Clinical Nutrition and Metabolism Background and aims: We have previously shown reduced protein balance in response to nutrition in paediatric Crohn's disease (CD) in remission, associated with reduced lean mass (sarcopenia) and reduced protein intake in males. We aim to compare skeletal muscle metabolic response to feeding in adult active CD and healthy volunteers. Methods: Eight CD participants with active disease (41.3 ± 4.5 yrs; BMI 26.9 ± 1.5 kg/m2) and eight matched healthy volunteers (Con) (41.2 ± 4.3 yrs; BMI 25.1 ± 1.1 kg/m2) were recruited. Participants had a dual energy X-ray absorptiometry scan, handgrip dynamometer test, wore a pedometer and completed a food diary. Arterialized hand and venous forearm blood samples were collected concurrently and brachial artery blood flow measured at baseline and every 20mins for 2hrs after the ingestion of a standardized mixed liquid meal. Net balance of branched chain amino acids (BCAA), glucose and free fatty acids across the forearm were derived. Results: No differences in muscle BCAA, glucose or FFA net balance were found between CD and Con. Neither were differences in muscle mass and function, physical activity or diet found. CD did not differ from Con in whole body insulin and lipid responses, or in energy expenditure and fuel oxidation. Conclusions: Skeletal muscle mass, function, dietary protein intake and response to a test meal in an adult CD cohort with active disease is similar to that seen in healthy volunteers. Combining these results with our previous findings in paediatric patients suggests that age of onset and/or disease burden over time, as well as daily protein intake, may be significant in the development of sarcopenia in CD. Longitudinal studies investigating these factors are required

An examination of resting-state functional connectivity in patients with active Crohn’s disease

Background: Alterations in resting state functional connectivity (rs-FC) in Crohn’s Disease (CD) have been documented in default mode network (DMN) and frontal parietal network (FPN) areas, visual, cerebellar, salience and attention resting-state-networks (RSNs), constituting a CD specific neural phenotype. To date, most studies are in patients in remission, with limited studies in active disease. Methods: 25 active CD cases and 25 age-, BMI- and gender-matched healthy controls (HC) were recruited to a resting-state-functional Magnetic Resonance Imaging (rs-fMRI) study. Active disease was defined as C-reactive protein>5mg/dl, faecal calprotectin>250μg/g, or through ileocolonoscopy or MRE. rs-fMRI data were analysed using independent component analysis (ICA) and dual regression. Differences in RSNs between HCs and active CD were assessed, and rs-FC was associated with disease duration and abdominal pain. Results: Increased connectivity in the FPN (fusiform gyrus, thalamus, caudate, posterior cingulate cortex, postcentral gyrus) and visual RSN (orbital frontal cortex) were observed in CD versus HC. Decreased activity was observed in the salience network (cerebellum, postcentral gyrus), DMN (parahippocampal gyrus, cerebellum), and cerebellar network (occipital fusiform gyrus, cerebellum) in CD versus HCs. Greater abdominal pain scores were associated with lower connectivity in the precuneus (visual network) and parietal operculum (salience network), and higher connectivity in the cerebellum (frontal network). Greater disease duration was associated with greater connectivity in the middle temporal gyrus and planum temporale (visual network). Conclusion: Alterations in rs-FC in active CD in RSNs implicated in cognition, attention, emotion, and pain may represent neural correlates of chronic systemic inflammation, abdominal pain, disease duration, and severity