Terminal ileitis: a rare gastrointestinal manifestation of IgA vasculitis in a child.

A girl in middle childhood was referred to the paediatric surgical team with acute colicky abdominal pain and bile-stained vomiting. This was preceded by a viral illness. Investigations revealed raised inflammatory markers, and imaging of the abdomen demonstrated ileal and jejunal thickening. Concerns were raised regarding whether she had inflammatory bowel disease. Endoscopy revealed gastritis and duodenitis, and colonoscopy was unremarkable. Video capsule endoscopy demonstrated ulcers in the jejunum and ileum.On day 8 of admission, she developed a symmetrical purpuric rash over both ankles leading to the diagnosis of Henoch-Schonlein-related ileitis. Multidisciplinary team working led to appropriate management of the patient and avoided surgery. Video capsule endoscopy enabled visualisation of the small bowel. She was managed with 5 days of methylprednisolone followed by oral steroids. She made a good recovery with no sequelae. This case highlighted that terminal ileitis is a rare complication of IgA vasculitis with a good prognosis.

Faecal calprotectin is not necessarily required as a screen for significant bowel disease in primary care.

OBJECTIVE: NICE recommends measurement of faecal haemoglobin (f-Hb) using faecal immunochemical test (FIT) when colorectal cancer is suspected and calprotectin (f-Cal) in the context of inflammatory bowel disease, though neither is disease specific. During the COVID-19 pandemic, f-Hb has been a requirement prior to referral for endoscopy in England; f-Cal is often performed simultaneously. The aim of this study was to investigate test performance of both tests for significant bowel disease in those patients referred. DESIGN: All adult patients with simultaneous measurements of f-Hb and f-Cal between April 2019 and September 2020 were included. For those referred, outcomes were determined from clinical records. RESULTS: 650 patients with simultaneous samples for f-Hb an f-Cal were managed in Primary Care; 319 patients were referred to hospital; SBD was found in 32 (10.0%) (CRC 5, high risk adenomas 5, IBD 22). At a cut-off of 10 µg/g for f-Hb and 200 µg/g for f-Cal, the sensitivity, specificity and negative predictive value for diagnosis of SBD were 84.4%, 58.2% and 96.7% and 68.8%, 89.6% and 95.7%, respectively. Performance of both tests would have enabled diagnosis of two more cases of significant, but non-malignant, bowel disease but required over 4% more referrals for investigation. CONCLUSION: Use of FIT has become established to assist prioritisation of patients for referral from Primary Care. Whilst introduced specifically for CRC, FIT performs well as a rule out for IBD in Primary Care and the use of f-Cal is not required.

Affective and enjoyment responses to 12 weeks of high intensity interval training and moderate continuous training in adults with Crohn's disease.

The aim was to undertake secondary data analysis from a three-arm randomised feasibility trial of high intensity interval training (HIIT), moderate intensity continuous training (MICT), and usual care control in adults with Crohn's disease (CD; n = 36), with a primary focus on exploring affective and enjoyment responses. Twenty-five participants with quiescent or mildly-active CD were randomised to one of the two exercise groups: HIIT (n = 13) and MICT (n = 12). Both groups were offered thrice weekly sessions for 12 weeks. MICT consisted of cycling for 30 minutes at 35% peak power (Wpeak), whereas HIIT involved ten 1-minute bouts at 90% Wpeak, interspersed with 1-minute bouts at 15% Wpeak. Heart rate (HR), differentiated ratings of perceived exertion for legs (RPE-L) and central (RPE-C), along with feeling state (Feeling Scale; FS) were measured at 92.5% of each session. Enjoyment was measured at the end of training using the Physical Activity Enjoyment Scale (PACES). Post-hoc exploratory analysis involved a mixed-model two-way ANOVA to compare HR, RPE-L, RPE-C and FS for the exercise sessions in weeks 1, 6 and 12 between groups. Overall, HR was greater (p < 0.01) during HIIT (173 ± 8 bpm) compared with MICT (128 ± 6 bpm). Similarly, RPE-L and RPE-C responses were greater overall (p = 0.03 and p = 0.03, respectively) during HIIT (5.5 ± 1.6 and 5.1 ± 1.7, respectively) compared to MICT (3.3 ± 1.5 and 2.9 ± 1.5, respectively). Overall, FS was 2.2 ± 1.9 for HIIT and 2.1 ± 1.4 for MICT with no effect of treatment group (p = 0.25) or time (p = 0.94). There was also no significant difference in PACES scores between HIIT (99.4 ± 12.9) and MICT (101.3 ± 17.4; p = 0.78). The findings suggest HIIT and MICT protocols elicited similar enjoyment and affect in adults with quiescent or mildly-active CD.

Reduced CD27-IgD- B Cells in Blood and Raised CD27-IgD- B Cells in Gut-Associated Lymphoid Tissue in Inflammatory Bowel Disease.

The intestinal mucosa in inflammatory bowel disease (IBD) contains increased frequencies of lymphocytes and a disproportionate increase in plasma cells secreting immunoglobulin (Ig)G relative to other isotypes compared to healthy controls. Despite consistent evidence of B lineage cells in the mucosa in IBD, little is known of B cell recruitment to the gut in IBD. Here we analyzed B cells in blood of patients with Crohn's disease (CD) and ulcerative colitis (UC) with a range of disease activities. We analyzed the frequencies of known B cell subsets in blood and observed a consistent reduction in the proportion of CD27-IgD- B cells expressing all Ig isotypes in the blood in IBD (independent of severity of disease and treatment) compared to healthy controls. Successful treatment of patients with biologic therapies did not change the profile of B cell subsets in blood. By mass cytometry we demonstrated that CD27-IgD- B cells were proportionately enriched in the gut-associated lymphoid tissue (GALT) in IBD. Since production of TNFα is a feature of IBD relevant to therapies, we sought to determine whether B cells in GALT or the CD27-IgD- subset in particular could contribute to pathology by secretion of TNFα or IL-10. We found that donor matched GALT and blood B cells are capable of producing TNFα as well as IL-10, but we saw no evidence that CD27-IgD- B cells from blood expressed more TNFα compared to other subsets. The reduced proportion of CD27-IgD- B cells in blood and the increased proportion in the gut implies that CD27-IgD- B cells are recruited from the blood to the gut in IBD. CD27-IgD- B cells have been implicated in immune responses to intestinal bacteria and recruitment to GALT, and may contribute to the intestinal inflammatory milieu in IBD.

High-intensity interval training and moderate-intensity continuous training in adults with Crohn's disease: a pilot randomised controlled trial.

BACKGROUND: This study assessed the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with Crohn's disease (CD). METHODS: In this mixed-methods pilot trial, participants with quiescent or mildly-active CD were randomly assigned 1:1:1 to HIIT, MICT or usual care control, and followed up for 6 months. The HIIT and MICT groups were offered three exercise sessions per week for the first 12 weeks. Feasibility outcomes included rates of recruitment, retention, outcome completion, and exercise attendance. Data were collected on cardiorespiratory fitness (e.g., peak oxygen uptake), disease activity, fatigue, quality of life, adverse events, and intervention acceptability (via interviews). RESULTS: Over 17 months, 53 patients were assessed for eligibility and 36 (68%) were randomised (47% male; mean age 36.9 [SD 11.2] years); 13 to HIIT, 12 to MICT, and 11 to control. The exercise session attendance rate was 62% for HIIT (288/465) and 75% for MICT (320/429), with 62% of HIIT participants (8/13) and 67% of MICT participants (8/12) completing at least 24 of 36 sessions. One participant was lost to follow-up. Outcome completion rates ranged from 89 to 97%. The mean increase in peak oxygen uptake, relative to control, was greater following HIIT than MICT (2.4 vs. 0.7 mL/kg/min). There were three non-serious exercise-related adverse events, and two exercise participants experienced disease relapse during follow-up. CONCLUSIONS: The findings support the feasibility and acceptability of the exercise programmes and trial procedures. A definitive trial is warranted. Physical exercise remains a potentially useful adjunct therapy in CD. [ID: ISRCTN13021107].

Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn's disease: study protocol for a randomised controlled trial.

BACKGROUND: Structured exercise training has been proposed as a useful adjunctive therapy for Crohn's disease by improving immune function and psychological health, reducing fatigue and promoting gains in muscle and bone strength. However, the evidence for exercise in Crohn's disease is sparse, with only a handful of small prospective trials [1, 2], with methodological limitations, including the use of non-randomised and non-controlled study designs and small sample sizes. Here, we describe the protocol for a study that aims to assess the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with inactive or mildly active Crohn's disease (CD). METHODS: This is a randomised, controlled, assessor-blinded, feasibility trial with three parallel groups. Forty-five adults with inactive or mildly active Crohn's disease will be randomly assigned 1:1:1 to HIIT, MICT or usual care control. Participants in the HIIT and MICT groups will be invited to undertake three sessions of supervised exercise each week for 12 consecutive weeks. HIIT sessions will consist of ten 1-min intervals of cycling exercise at 90% of peak power output separated by 1 min of active recovery. MICT sessions will involve 30 min of continuous cycling at 35% of peak power output. Participants will be assessed before randomisation and 13 and 26 weeks after randomisation. Feasibility outcomes include rates of recruitment, retention and adherence. Interviews with participants will explore the acceptability of the exercise programmes and study procedures. Clinical/health outcomes include cardiorespiratory fitness, body mass index, resting blood pressure, markers of disease activity (faecal calprotectin and Crohn's Disease Activity Index) and activated T cell cytokine profiles. Study questionnaires include the Inflammatory Bowel Disease Quality of Life Questionnaire, EQ-5D-5L, IBD Fatigue Scale, Hospital and Anxiety Depression Scale, and International Physical Activity Questionnaire. DISCUSSION: This study will provide useful information on the feasibility and acceptability of supervised exercise training in adults with inactive and mildly active Crohn's disease and will inform the design of a subsequent, adequately powered, multi-centre trial. TRIAL REGISTRATION: The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN13021107). Date registration assigned was 02/12/2015.

Small bowel video capsule endoscopy: an overview.

Video capsule endoscopy (VCE) is being increasingly used to investigate small bowel pathology. It is the gold standard for obscure gastrointestinal bleeding and iron deficiency anemia. VCE has been in use since 2001 and indications for its use are expanding. VCE is also a useful diagnostic tool in small bowel Crohn's disease, celiac disease, surveillance of polyps, small bowel malignancy and drug-induced small bowel injury. Although VCE is considered a safe and easy procedure, there are a few limitations. These include cost, capsule retention and inability to take a biopsy and perform any therapeutic maneuvers. Contraindications for VCE include pregnancy, patients with a swallowing disorder, history of previous abdominal surgery or concurrent abdomino-pelvic irradiation. This is an overview of VCE, its role and indications in clinical practice, potential complications and contraindications, as well as the ongoing and expected advances in the field.

High resolution colonoscopy in a bowel cancer screening program improves polyp detection.

AIM: To compare high resolution colonoscopy (Olympus Lucera) with a megapixel high resolution system (Pentax HiLine) as an in-service evaluation. METHODS: Polyp detection rates and measures of performance were collected for 269 colonoscopy procedures. Five colonoscopists conducted the study over a three month period, as part of the United Kingdom bowel cancer screening program. RESULTS: There were no differences in procedure duration (χ² P = 0.98), caecal intubation rates (χ² P = 0.67), or depth of sedation (χ² P = 0.64). Mild discomfort was more common in the Pentax group (χ² P = 0.036). Adenoma detection rate was significantly higher in the Pentax group (χ² test for trend P = 0.01). Most of the extra polyps detected were flat or sessile adenomas. CONCLUSION: Megapixel definition colonoscopes improve adenoma detection without compromising other measures of endoscope performance. Increased polyp detection rates may improve future outcomes in bowel cancer screening programs.

Survival following Treatment of Aortoesophageal Fistula with Dual Esophageal and Aortic Intervention.

Aortoesophageal fistulas are a rare but commonly fatal complication of esophageal cancer. Reports of successfully managed cases are few, with high mortality and morbidity usually resulting from failure to control the initial massive haemodynamic insult. We report the case of a 47-year-old Caucasian man with recently diagnosed advanced esophageal cancer who suffered an episode of massive haematemesis. Emergency gastroscopy revealed an arterial bleeding point in the proximal esophagus. A self-expanding metal esophageal stent was placed to achieve initial partial haemostasis. CT angiography confirmed an aortoesophageal fistula. An endoluminal stent device was thus inserted within the thoracic aorta stabilising the bleeding point. The patient subsequently made an uneventful recovery and was discharged on long-term antibiotics for palliative care. He survived for 2 months at home before dying of disseminated malignancy. The successful use of esophageal stenting as a means of achieving haemostasis, allowing time for endovascular intervention, is as yet a relatively unexplored area of management of this rare condition.

The effect of hypnosis on systemic and rectal mucosal measures of inflammation in ulcerative colitis.

OBJECTIVES: Hypnotherapy is effective in several diseases with a psychosomatic component. Our aim was to study the effects of one session of hypnosis on the systemic and rectal mucosal inflammatory responses in patients with active ulcerative colitis (UC). METHODS: In total, 17 patients with active UC underwent a 50-min session of gut-focused hypnotherapy. Before and after each procedure, the systemic inflammatory response was assessed by serum interleukin (IL)-6 and IL-13 concentrations, tumor necrosis factor-alpha (TNF-alpha) and IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood, leukocyte count, natural killer (NK) cell number, platelet activation, and platelet-leukocyte aggregate formation. Rectal inflammation was assessed by mucosal release of substance P (SP), histamine, IL-13 and TNF-alpha, reactive oxygen metabolite production, and mucosal blood flow. Eight patients with active UC underwent a control procedure. RESULTS: Hypnosis decreased pulse by a median 7 beats per minute (bpm) (P= 0.0008); it also reduced the median serum IL-6 concentration by 53% (P= 0.001), but had no effect on the other systemic variables assessed. Hypnosis reduced rectal mucosal release of SP by a median 81% (P= 0.001), histamine by 35% (P= 0.002) and IL-13 by 53% (P= 0.003), and also, blood flow by 18% (P= 0.0004). The control protocol had no effect on any of the variables assessed. CONCLUSIONS: Hypnosis reduced several components of the systemic and mucosal inflammatory response in active ulcerative colitis toward levels found previously in the inactive disease. Some of these effects may contribute to the anecdotally reported benefits of hypnotherapy and provide a rationale for controlled trials of hypnotherapy in UC.

The effect of acute psychologic stress on systemic and rectal mucosal measures of inflammation in ulcerative colitis.

BACKGROUND & AIMS: Recent studies suggest that life events and chronic stress increase the risk of relapse in inflammatory bowel disease. Our aim was to study the effects of acute psychologic stress on systemic and rectal mucosal inflammatory responses in patients with inactive ulcerative colitis (UC). METHODS: Twenty-five patients with inactive UC and 11 healthy volunteers (HV) underwent an experimental stress test. Ten patients with UC and 11 HV underwent a control procedure. Before and after each procedure, systemic inflammatory response was assessed by serum interleukin (IL)-6 and IL-13 concentrations, tumor necrosis factor (TNF)-alpha and IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood, leukocyte count, natural killer (NK) cell numbers, platelet activation, and platelet-leukocyte aggregate (PLA) formation. In patients with UC, rectal mucosal inflammation was assessed by TNF-alpha, IL-13, histamine and substance P release, reactive oxygen metabolite (ROM) production, mucosal blood flow (RMBF) and histology. RESULTS: Stress increased pulse (P < .0001) and systolic BP (P < .0001). In UC, stress increased LPS-stimulated TNF-alpha and IL-6 production by 54% (P = .004) and 11% (P = .04), respectively, leukocyte count by 16% (P = .01), NK cell count by 18% (P = .0008), platelet activation by 65% (P < .0001), PLA formation by 25% (P = .004), mucosal TNF-alpha release by 102% (P = .03), and ROM production by 475% (P = .001) and reduced rectal mucosal blood flow by 22% (P = .05). The control protocol did not change any of the variables measured. There were no differences between the responses of the patients with UC and HV. CONCLUSIONS: Acute psychologic stress induces systemic and mucosal proinflammatory responses, which could contribute to exacerbations of UC in ordinary life.

Formation of platelet-leukocyte aggregates in inflammatory bowel disease.

OBJECTIVES: Formation of platelet-leukocyte aggregates (PLAs) is increased in several inflammatory and thrombotic conditions. This may result from and enhance platelet and neutrophil activation and could contribute to the inflammatory process in inflammatory bowel disease (IBD). We investigated platelet-leukocyte aggregation in patients with IBD and its relation to treatment, disease activity and platelet and neutrophil activation. METHODS: PLAs, platelet activation (P-selectin expression) and neutrophil activation (L-selectin expression) were assessed 30 and 180 minutes after drawing blood into EDTA/citrate-theophylline-adenosine and dipyridamole, a novel anticoagulant, using fluorescent antibodies to CD45 (for leukocytes), CD42a (for platelets), CD62P (P-selectin) and CD62L (L-selectin) and flow cytometry. Platelet activation was also measured using the ADVIA 120 hematology analyser. RESULTS: Samples from 67 patients with IBD measured within 30 minutes had a higher platelet count (P < 0.001), more platelets expressing P-selectin (P = 0.01), and more PLAs (P < 0.01) than from 20 healthy controls and more PLAs (P < 0.05) than from 9 controls with inflammatory arthropathies. IBD patients on thiopurines had fewer PLAs than those not taking them (P < 0.05); corticosteroids and aminosalicylates had no such effects. Incubation for 180 minutes increased the number of platelets expressing P-selectin (P < 0.0001), and the number of PLAs (P < 0.0001). The PLAs correlated with the number of platelets expressing P-selectin before (r=+0.40, P < 0.001) and after (r=+0.66, P < 0.0001) incubation. CONCLUSIONS: The number of PLAs is higher in patients with IBD than in healthy and inflammatory controls, but their numbers are lowered by thiopurines. Increased PLA formation may in part be due to increased platelet activation and could be pathogenic in IBD.

Enteric infection in relapse of inflammatory bowel disease: importance of microbiological examination of stool.

OBJECTIVE: Previous reports have suggested that diarrhoeal relapses of inflammatory bowel disease (IBD) may be associated or confused with enteric infection, and that treatment of such infections with appropriate antibiotics may be beneficial. To re-evaluate the suggestion that enteric infection is rare and microbiological testing of stool not routinely necessary in patients presenting with relapse of IBD, we have reviewed the incidence of concurrent infection in patients presenting in relapse over a recent 5-year period. METHODS: Stool microbiology results relating to relapses of IBD during the period 1997-2001 were obtained retrospectively. Relapse was confirmed by standard clinical, sigmoidoscopic and laboratory criteria. RESULTS: During the period 1997-2001 there were 237 relapses in 213 patients. Enteric infection was found in 25 (10.5%) relapses in 24 patients; in seven patients, infection was associated with the initial presentation of their IBD. Clostridium difficile toxin was detected in 13 (5.5%) instances; the 12 other infections (5% relapses) were Campylobacter spp. (five), Entamoeba histolytica (three), Salmonella spp. (one), Plesiomonas shigelloides (one), Strongyloides stercoralis (one) and Blastocystis hominis (one). There was a significant association between infection and the need for hospital admission. Of the 13 relapses associated with C. difficile, ten were in outpatients, seven patients had undergone previous antibiotic treatment, and four patients were presenting with IBD for the first time. All relapses resolved satisfactorily after treatment with antibiotics with or without corticosteroids. CONCLUSIONS: The high prevalence of enteric infections, of which C. difficile was the most common, indicates that all patients presenting with relapse of IBD should have stool examined microbiologically.

Use of complementary therapies by patients with IBD may indicate psychosocial distress.

BACKGROUND: Complementary and alternative medicine (CAM) is used increasingly by patients with chronic diseases. We have assessed the use of CAM in general medicine and gastrointestinal outpatients focusing particularly on factors predisposing to its use in patients with inflammatory bowel disease (IBD). METHODS: 239 consecutive patients attending gastrointestinal and general medical outpatient clinics answered a questionnaire about their use of CAM: patients with IBD also completed a validated disease-specific quality of life (QOL) inflammatory bowel disease questionnaire (IBDQ). RESULTS: 26% of all patients used CAM, most commonly herbal remedies (43%). CAM was used significantly more by younger than older patients and by single than married or widowed ones. There were no differences by gender or ethnicity. More patients with irritable bowel syndrome used CAM than those with other diagnoses. In IBD patients, CAM users had significantly poorer QOL scores for emotional and social factors than nonusers. 53% of users stated that CAM alleviated their symptoms. CONCLUSIONS: Use of CAM is common in gastroenterological outpatients, particularly if they are young, single, or have irritable bowel syndrome (IBS). Most patients deem it helpful. In IBD, poor QOL predisposes to use of CAM. Conversely, use of CAM may serve as a marker of emotional or social unease in these patients. Physicians need to be aware of widespread usage of CAM by their patients.