Association between antidepressant medication use and steroid dependency in patients with ulcerative colitis: a population-based study.

BACKGROUND: Animal studies indicate a potential protective role of antidepressant medication (ADM) in models of colitis but the effect of their use in humans with ulcerative colitis (UC) remains unclear. OBJECTIVE: To study the relationship between ADM use and corticosteroid dependency in UC. DESIGN: Using the Clinical Practice Research Datalink we identified patients diagnosed with UC between 2005 and 2016. We grouped patients according to serotonin selective reuptake inhibitor (SSRI) and tricyclic antidepressant (TCA) exposure in the 3 years following diagnosis: 'continuous users', 'intermittent users' and 'non-users'. We used logistic regression to estimate the adjusted risk of corticosteroid dependency between ADM exposure groups. RESULTS: We identified 6373 patients with UC. Five thousand two hundred and thirty (82%) use no ADMs, 627 (10%) were intermittent SSRI users and 282 (4%) were continuous SSRI users, 246 (4%) were intermittent TCA users and 63 (1%) were continuous TCA users.Corticosteroid dependency was more frequent in continuous SSRI and TCA users compared with non-users (19% vs 24% vs 14%, respectively, χ2 p=0.002). Intermittent SSRI and TCA users had similar risks of developing corticosteroid dependency to non-users (SSRI: OR 1.19, 95% CI 0.95 to 1.50, TCA: OR 1.14, 95% CI 0.78 to 1.66). Continuous users of both SSRIs and TCAs had significantly higher risks of corticosteroid dependency compared with non-users (SSRI: OR 1.62, 95% CI 1.15 to 2.27, TCA: OR 2.02, 95% CI 1.07 to 3.81). CONCLUSIONS: Continuous ADM exposure has no protective effect in routine clinical practice in UC and identifies a population of patients requiring more intensive medical therapy. ADM use is a flag for potentially worse clinical outcomes in UC.

Depression in individuals who subsequently develop inflammatory bowel disease: a population-based nested case-control study.

OBJECTIVE: Depression is a potential risk factor for developing IBD. This association may be related to GI symptoms occurring before diagnosis. We aimed to determine whether depression, adjusted for pre-existing GI symptoms, is associated with subsequent IBD. DESIGN: We conducted a nested case-control study using the Clinical Practice Research Datalink identifying incident cases of UC and Crohn's disease (CD) from 1998 to 2016. Controls without IBD were matched for age and sex. We measured exposure to prevalent depression 4.5-5.5 years before IBD diagnosis. We created two sub-groups with prevalent depression based on whether individuals had reported GI symptoms before the onset of depression. We used conditional logistic regression to derive ORs for the risk of IBD depending on depression status. RESULTS: We identified 10 829 UC cases, 4531 CD cases and 15 360 controls. There was an excess of prevalent depression 5 years before IBD diagnosis relative to controls (UC: 3.7% vs 2.7%, CD 3.7% vs 2.9%). Individuals with GI symptoms prior to the diagnosis of depression had increased adjusted risks of developing UC and CD compared with those without depression (UC: OR 1.47, 95% CI 1.21 to 1.79; CD: OR 1.41, 95% CI 1.04 to 1.92). Individuals with depression alone had similar risks of UC and CD to those without depression (UC: OR 1.13, 95% CI 0.99 to 1.29; CD: OR 1.12, 95% CI 0.91 to 1.38). CONCLUSIONS: Depression, in the absence of prior GI symptoms, is not associated with subsequent development of IBD. However, depression with GI symptoms should prompt investigation for IBD.

Comparison of small intestinal contrast ultrasound with magnetic resonance enterography in pediatric Crohn's disease.

AIM: To compare the diagnostic yield of small intestinal contrast ultrasonography (SICUS) with magnetic resonance enterography (MRE) in routine clinical practice in a cohort of pediatric patients investigated for Crohn's disease (CD) attending a UK tertiary center. METHODS AND RESULTS: Patients with suspected or established CD who underwent SICUS were identified retrospectively. SICUS was compared to conventional transabdominal ultrasound (TUS), ileocolonoscopy (IC), and MRE. The accuracy and agreement of SICUS in detecting small bowel lesions and CD-related complications were assessed using kappa (κ) coefficient statistics. A total of 93 patients (median age 15 years, range 2-17, 49 male) underwent SICUS; 58 had suspected and 35 had established CD. In suspected CD, sensitivity and specificity of SICUS in detecting CD small bowel lesions were 81.8 and 100% and for TUS 85.7 and 87.5%, respectively. In established CD, sensitivity and specificity of SICUS were 98.7 and 100% and TUS 80 and 100%, respectively. Agreement between SICUS and IC was substantial for the presence of lesions (κ = 0.73) but fair in TUS (κ = 0.31). Agreement between SICUS and IC was almost perfect for detecting strictures (κ = 0.84), with a sensitivity of 100% and specificity of 97.6%. When comparing SICUS and TUS with MRE, agreement for the presence of lesions was substantial (κ = 0.63) and moderate (κ = 0.53), respectively. Agreement between SICUS and MRE was substantial for detecting strictures (κ = 0.77) and dilatation (κ = 0.68). CONCLUSIONS: SICUS offers a radiation-free alternative for assessing pediatric small bowel CD, with diagnostic accuracy that is comparable to MRE and IC, supporting its wider use in routine practice.

The impact of smoking and smoking cessation on disease outcomes in ulcerative colitis: a nationwide population-based study.

BACKGROUND: Smokers are less likely to develop ulcerative colitis (UC) but the impact of smoking and subsequent cessation on clinical outcomes in UC is unclear. AIM: To evaluate the effect of smoking status and smoking cessation on disease outcomes. METHODS: Using a nationally representative clinical research database, we identified incident cases of UC during 2005-2016. Patients were grouped as never-smokers, ex-smokers and smokers based on smoking status recorded in the 2 years preceding UC diagnosis. We defined subgroups of persistent smokers and smokers who quit within 2 years after diagnosis. We compared the rates of overall corticosteroid use, corticosteroid-requiring flares, corticosteroid dependency, thiopurine use, hospitalisation and colectomy between these groups. RESULTS: We identified 6754 patients with a new diagnosis of UC over the study period with data on smoking status, of whom 878 were smokers at diagnosis. Smokers had a similar risk of corticosteroid-requiring flares (OR 1.16, 95% CI 0.92-1.25), thiopurine use (HR 0.84, 95% CI 0.62-1.14), corticosteroid dependency (HR 0.85, 95% CI 0.60-1.11), hospitalisation (HR 0.92, 95% CI 0.72-1.18) and colectomy (HR 0.78, 95% CI 0.50-1.21) in comparison with never-smokers. Rates of flares, thiopurine use, corticosteroid dependency, hospitalisation and colectomy were not significantly different between persistent smokers and those who quit smoking after a diagnosis of UC. CONCLUSIONS: Smokers and never-smokers with UC have similar outcomes with respect to flares, thiopurine use, corticosteroid dependency, hospitalisation and colectomy. Smoking cessation was not associated with worse disease course. The risks associated with smoking outweigh any benefits. UC patients should be counselled against smoking.

Smoking Status at Diagnosis and Subsequent Smoking Cessation: Associations With Corticosteroid Use and Intestinal Resection in Crohn's Disease.

BACKGROUND: The impact of smoking at diagnosis and subsequent smoking cessation on clinical outcomes in Crohn's disease (CD) has not been evaluated in a population-based cohort. METHODS: Using a nationally representative clinical research database, we identified incident cases of CD between 2005 and 2014. We compared the following outcomes: overall corticosteroid (CS) use; flares requiring CS; CS dependency and intestinal surgery between smokers and non-smokers at time of CD diagnosis. Differences in these outcomes were also compared between persistent smokers and smokers who quit within 2 years of diagnosis. RESULTS: We identified 3553 patients with a new CD diagnosis over the study period of whom 1121 (32%) were smokers. Smokers at CD diagnosis had significantly higher CS-use (56 versus 47%, p < 0.0001), proportionally more CS flares (>1 CS flare/year: 9 versus 6%, p < 0.0001), and higher CS dependency (27 versus 21%, p < 0.0001) than non-smokers. Regression analysis identified smoking at diagnosis to be associated with a higher risk of intestinal surgery (HR 1.64, 95% CI 1.16-2.52). There was a significantly higher proportion of 'quitters' who remained steroid-free through follow-up in comparison to 'persistent smokers' (45.4 versus 37.5%, respectively, p = 0.02). 'Quitters' also had lower rates of CS dependency compared to 'persistent smokers' (24 versus 33%, p = 0.008). CONCLUSIONS: Smokers at CD diagnosis have higher CS-use, CS dependency and higher risk of intestinal surgery. Quitting smoking appears to have beneficial effects on disease related outcomes, including reducing CS dependency highlighting the importance of offering early smoking cessation support.

Do Thiopurines Reduce the Risk of Surgery in Elderly Onset Inflammatory Bowel Disease? A 20-Year National Population-Based Cohort Study.

BACKGROUND: Evidence that thiopurines impact on the risk of surgery in elderly onset inflammatory bowel disease (EO-IBD) is lacking. We aimed to compare the rates of surgery in EO-IBD (>60 years at diagnosis) with adult-onset IBD (18-59 yrs), and examine the impact of thiopurines on surgical risk in EO-IBD. METHODS: Using a U.K. database between 1990 and 2010, we compared rates of surgery between adult-onset IBD and EO-IBD using survival analysis. Ulcerative colitis (UC) and Crohn's disease (CD) were analyzed separately. Cox proportional hazard modeling was used to determine the adjusted relative risk of surgery. We further assessed the impact of duration of thiopurine treatment on risk of surgery. RESULTS: We identified 2758 of 9515 patients with UC and 1349 of 6490 patients with CD, with EO-IBD. Cumulative 1, 5, and 10 years risk of colectomy was similar in EO-UC (2.2, 4.5, and 5.8%, respectively) and AO-UC (2.2, 5.0, and 7.3%, respectively; P = 0.15). Cumulative 1, 5, and 10 years risk of first intestinal surgery was lower in EO-CD (9.5, 14.6, and 17.9%, respectively) than AO-CD (12.2, 19.0, and 24.4%, respectively; P < 0.001). Early steroid use, steroid dependency, and thiopurine use was associated with higher risk of colectomy in EO-UC. Among EO-UC receiving thiopurines for >12 months, there was a 70% reduction in risk of colectomy (hazard ratio. 0.30; 95% confidence interval, 0.15-0.58). Thiopurines were not associated with a reduced risk of surgery in EO-CD. CONCLUSIONS: Risk of colectomy in EO-UC does not differ from AO-UC, but the risk of surgery in EO-CD is significantly lower than in AO-CD. Sustained thiopurine use of 12 months or more duration in EO-UC reduces the risk colectomy, but does not impact on the risk of surgery in EO-CD. These findings are important given the greater risk of thiopurine-associated lymphoma in the elderly.

Ano-genital Granulomatosis and Crohn's Disease: A Case Series of Males Presenting with Genital Lymphoedema.

BACKGROUND AND AIMS: Ano-genital granulomatosis is a rare chronic granulomatous condition of the skin that causes lymphoedema of the external genitalia. There is a reported association with Crohn's disease. Mechanisms of disease and optimal methods of treatment are poorly understood. METHODS: A retrospective casenote review of 25 male patients with ano-genital granulomatosis presenting with genital lymphoedema was performed to determine the clinical and histopathological features of this condition and its relationship to intestinal Crohn's disease. RESULTS: A combination of penile and scrotal oedema was reported at presentation in 80% of patients; 40% of patients had associated intestinal Crohn's disease. The average time from symptom onset to diagnosis was 52.7 months. Half of cutaneous biopsies contained non-caseating granulomas and 14% contained intralymphatic granulomas. In all, 72% of patients responded to oral steroids initially but recurrence was common. Complete or partial response was achieved in 60% of patients treated with azathioprine. Three of six patients responded to anti-tumour necrosis factor [TNF] therapy. A small proportion of patients required circumcision or de-bulking surgery for more debilitating disease. CONCLUSIONS: Ano-genital granulomatosis is a rare condition that presents with genital lymphoedema, and there is frequently a protracted delay in diagnosis. There is a very strong association with intestinal Crohn's disease. Genital lymphoedema associated with gastrointestinal symptoms should prompt careful evaluation to exclude both ano-genital granulomatosis and Crohn's disease.

Delayed diagnosis of lymphogranuloma venereum-associated colitis in a man first suspected to have rectal cancer.

Lymphogranuloma venereum-associated colitis is a diagnosis that should not be missed. The following case represents the importance of a thorough history, including the importance of the sexual history to prevent the misdiagnosis of these patients.

Proposed case of mesalazine-induced cardiomyopathy in severe ulcerative colitis.

Five-amino salicylic acids are recommended for use in the management of inflammatory bowel disease, cardiac complications are a rare although recognised phenomenon. This report aims to highlight this serious but rare adverse reaction. We report here a case of a young man presenting with cardiogenic shock in the context of recent mesalazine treatment in severe ulcerative colitis.

Inflammatory bowel disease in young patients: challenges faced by black and minority ethnic communities in the UK.

There is strong evidence indicating that inflammatory bowel disease (IBD) is increasing among black and minority ethnic (BME) communities. Despite this rise in prevalence, there is a paucity of research relating to ethnicity and IBD outside the USA. Furthermore, the symptoms of IBD are reported to start during childhood or adolescence in 20-25% of people with the condition. It is therefore important that young people's experiences of diagnosis, treatment and living with IBD are fully understood to ensure effective services and information provision. The study reported on in this paper was commissioned by a UK charity (Crohn's and Colitis UK) with the aim of increasing understanding of the specific issues and service needs of young people with IBD from BME communities. Empirical research entailed in-depth semi-structured interviews with 20 young people from BME groups accessed through gastroenterology departments at three collaborating NHS hospitals in England serving ethnically diverse populations. Interviews were carried out from June to December 2010 and sought to capture young people's views with IBD. A thematic analysis of their experiences identified many commonalities with other young people with IBD, such as the problematic route to formal diagnosis and the impact of IBD on education. The young people also experienced tensions between effective self-management strategies and cultural norms and practices relating to food. Moreover, the ability of parents to provide support was hampered for some young people by the absence of culturally competent services that were responsive to the families' communication needs. The findings highlight the need for more culturally appropriate information concerning IBD, and improved responsiveness to young people with IBD within primary care and the education system, as well as culturally competent messaging relating to the specific nature of the condition among the wider South Asian and black communities.

Impact of thiopurines and anti-tumour necrosis factor therapy on hospitalisation and long-term surgical outcomes in ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory condition affecting the large bowel and is associated with a significant risk of both requirement for surgery and the need for hospitalisation. Thiopurines, and more recently, anti-tumour necrosis factor (aTNF) therapy have been used successfully to induce clinical remission. However, there is less data available on whether these agents prevent long-term colectomy rates or the need for hospitalisation. The focus of this article is to review the recent and pertinent literature on the long-term impact of thiopurines and aTNF on long-term surgical and hospitalisation rates in UC. Data from population based longitudinal research indicates that thiopurine therapy probably has a protective role against colectomy, if used in appropriate patients for a sufficient duration. aTNF agents appear to have a short term protective effect against colectomy, but data is limited for longer periods. Whereas there is insufficient evidence that thiopurines affect hospitalisation, evidence favours that aTNF therapy probably reduces the risk of hospitalisation within the first year of use, but it is less clear on whether this effect continues beyond this period. More structured research needs to be conducted to answer these clinically important questions.

Small intestinal contrast ultrasonography for the detection of small bowel complications in Crohn's disease: correlation with intraoperative findings and magnetic resonance enterography.

BACKGROUND AND AIMS: In evaluating small bowel Crohn's disease (CD), small intestine contrast-enhanced ultrasonography (SICUS) is emerging as an alternative to magnetic resonance enterography (MRE). This retrospective study compared the diagnostic accuracy of SICUS and MRE with surgical findings, and their level of agreement. METHODS: We identified a cohort of CD patients investigated by either SICUS and/or MRE that subsequently required resective bowel surgery within 6 months. The accuracy and agreement of SICUS and MRE to detect small bowel complications were compared with intraoperative findings using kappa coefficient (κ). Agreement between SICUS and MRE in those undergoing both modalities was also assessed. RESULTS: A total of 67 patients were evaluated; 25 underwent SICUS and 17 underwent MRE prior to surgery. Another 25 patients underwent both SICUS and MRE. When compared with intraoperative findings, the sensitivity of SICUS and MRE was 87.5% and 100%, respectively, in detecting strictures, 87.7% and 66.7% for fistulae, 100% for both in identifying abscesses, 100% and 66.7% for bowel dilatation, and 94.7% and 81.8% in defining bowel wall thickening. When correlating SICUS and MRE with surgery, there was a high level of agreement in localizing strictures (κ = 0.75, 0.88, respectively), fistulae (κ = 0.82, 0.79) and abscesses (κ = 0.87, 0.77). Concordance between SICUS and MRE was substantial or almost complete in identifying stricturing disease (κ = 0.84), their number and location (κ = 0.85), fistulae (κ = 0.65), and mucosal thickening (κ = 0.61). CONCLUSION: SICUS accurately identified small bowel complications and correlated well with MRE and intraoperative findings. SICUS offers an alternative in the preoperative assessment of CD.

Determinants of Weight Loss prior to Diagnosis in Inflammatory Bowel Disease: A Retrospective Observational Study.

Aims. To identify prevalence, severity, and environmental determinants of weight loss in inflammatory bowel disease (IBD) patients just prior to time of formal diagnosis. Methodology. IBD patients attending outpatient clinic were questioned about weight loss prior to diagnosis and other environmental and demographic variables. The percentage BMI loss was calculated for each subject and factors associated with weight loss were determined. Results. Four hundred and ninety-four subjects were recruited (237 cases of Crohn's disease (CD) and 257 cases of ulcerative colitis (UC)). Overall, 57% of subjects with CD and 51% of subjects with UC experienced significant weight loss prior to diagnosis (>5% BMI loss). Younger age at diagnosis and history of previous IBD surgery were significantly associated with both lower BMI at diagnosis and increased weight loss prior to diagnosis. In CD patients, increasing age at diagnosis was inversely associated with weight loss prior to diagnosis. Ileal disease was a risk factor of weight loss, whereas prior appendectomy was associated with reduced risk of weight loss. Conclusions. Weight loss is a significant problem for many IBD patients at presentation, especially in younger age and CD with ileal involvement. Appendectomy is associated with diminished weight loss.

Primary pulmonary mucinous cystadenocarcinoma presenting as a complex bronchocele: a case report.

INTRODUCTION: Primary pulmonary mucinous cystadenocarcinoma is a rare variety of lung cancer. It is characterized pathologically by copious mucin production predominantly in the extracellular space. This tumour has a remarkably favorable prognosis. CASE PRESENTATION: We present imaging and histopathological findings of primary pulmonary mucinous cystadenocarcinoma presenting as a complex bronchocele in a 67-year-old Caucasian woman. CONCLUSION: Diagnosis of pulmonary mucinous cystadenocarcinoma should be considered in patients presenting with bronchocele that has suspicious imaging features, because the results of fine needle aspiration cytology and bronchoscopy are frequently inconclusive in these tumours. Positive emission tomography has an important role in helping to identify these tumours.