128 research outputs found
Case Report:Systemic Small-Vessel Vasculitis in an Adolescent With Active Ulcerative Colitis
Introduction: Small-vessel vasculitis (SVV) is a rare immunological disease that affects arterioles, capillaries and venules. It causes purpura, but can also manifest in other organs, including the gastrointestinal tract. SVV and inflammatory bowel disease (IBD) co-occur more frequently than would be expected by chance. Case description: A 16-year-old girl, who had been diagnosed with ulcerative colitis (UC) 2 years earlier at a general hospital, developed purpura, progressive abdominal pain with frequent bloody diarrhea and frontotemporal headache and swelling while on azathioprine and mesalamine maintenance therapy. Serology was positive for perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) without antiprotease- or myeloperoixidase antibodies. Endoscopy revealed active left-sided UC and atypical ulcerations in the ascending colon. Biopsies of these ulcerations and of affected skin revealed leukocytoclastic vasculitis. Initially this was interpreted as an extraintestinal manifestation of UC that would subside when remission was induced, consequently infliximab was started. Over the next 3 weeks she developed severe burning pain in her right lower leg that progressed to a foot drop with numbness and the purpura progressed to bullous lesions. The diagnosis was adjusted to ANCA-associated vasculitis with involvement of skin, bowel and peripheral nerves. Infliximab was discontinued and induction treatment with high-dose prednisolone and cyclophosphamide was given until remission of SVV and UC was achieved. Subsequently, infliximab induction and maintenance was re-introduced in combination with methotrexate. Remission has been maintained successfully for over 2 years now. The foot drop only partly resolved and necessitated the use of an orthosis. Conclusion: Pediatric patients with IBD who present with purpuric skin lesions and abdominal pain should be evaluated for systemic involvement of SVV, which includes endoscopic evaluation of the gastrointestinal tract. We discuss a practical approach to the diagnosis, evaluation and management of systemic SVV with a focus on prompt recognition and early aggressive therapy to improve outcome
De-Escalation of Anti-Tumor Necrosis Factor Alpha Agents and Reduction in Adverse Effects:A Systematic Review
Background: The long-term use of anti-TNF-alpha agents can lead to adverse effects, such as infections and immune-mediated cutaneous reactions. Whether de-escalation by dose reduction or interval lengthening reduces these adverse effects is uncertain. This systematic review aims to compare the incidence of infections and skin manifestations after anti-TNF-alpha dose de-escalation with standard dosing. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception to January 14, 2022. Randomized controlled trials (RCTs) and observational studies comparing anti-TNF-alpha-de-escalation strategies with standard dosing among patients with inflammatory conditions, that report on infections, skin manifestations, or both, were included. The risk of bias was assessed with the revised Cochrane risk-of bias tool (RCTs) or the Newcastle-Ottawa scale (non-RCTs). Results: Fourteen RCTs and six observational studies (or 2706 patients) were included. Eight RCTs had low risk of bias or some concerns. Four non-RCTs were of good methodological quality. The studies described patients with axial spondyloarthritis (8 studies, 780 patients), rheumatoid arthritis (7 studies, 1458 patients), psoriasis (3 studies, 332 patients), or inflammatory bowel disease (2 studies, 136 patients). De-escalation strategies included interval lengthening (12 studies, 1317 patients), dose reduction (6 studies, 1130 patients), or both (2 studies, 259 patients). Overall, the occurrence of infections and skin manifestations did not differ between standard treatment and de-escalation. The disappearance of infections or skin manifestations after de-escalation was only reported in two studies. The majority of studies focused on etanercept and adalimumab. Heterogeneity in reporting of infections and skin manifestations precluded metaanalysis. Conclusion: We found that anti-TNF-alpha de-escalation does not reduce infections or skin reactions. A de-escalation strategy should not be recommended for the sole purpose of reducing drug-related adverse effects. The meticulous documentation of adverse effects is recommended to further address this question
Ustekinumab trough levels in children with Crohn’s disease refractory to anti-tumor necrosis factor agents: a prospective case series of off-label use
Background: Ustekinumab is used off-label in pediatric Crohn’s disease refractory to anti-tumor necrosis factor. Data on optimal dosing, target trough levels, and potential benefit of therapeutic drug monitoring in children treated with ustekinumab are limited.Materials and Methods: We describe a series of six adolescents who consented to be treated with ustekinumab. We measured their trough levels, C-reactive protein, and fecal calprotectin before every administration.Results: Standard adult dosing was effective to achieve biochemical remission (fecal calprotectin < 250 mg/kg) in one patient and clinical remission (resolution of symptoms) in another. The other four patients failed to respond on standard dosing and underwent intravenous re-induction and interval shortening to increase ustekinumab trough levels. This resulted in biochemical remission in one patient and clinical remission in another, suggesting an exposure–response relationship. The remaining two patients had no therapeutic benefit, and ustekinumab was discontinued.Conclusion: In this report, we show that ustekinumab can induce remission in pediatric patients with anti-tumor necrosis factor refractory Crohn’s disease. It is worth escalating the dose before abandoning the drug as ineffective. Prospective studies in children are needed to determine long-term efficacy of ustekinumab, usefulness of therapeutic drug monitoring strategies, and, if applicable, optimal target trough levels
Clinical Utility of Fecal Calprotectin Monitoring in Asymptomatic Patients with Inflammatory Bowel Disease:A Systematic Review and Practical Guide
Background: In asymptomatic patients with inflammatory bowel disease (IBD), "monitoring" involves repeated testing aimed at early recognition of disease exacerbation. We aimed to determine the usefulness of repeated fecal calprotectin (FC) measurements to predict IBD relapses by a systematic literature review. Methods: An electronic search was performed in Medline, Embase, and Cochrane from inception to April 2016. Inclusion criteria were prospective studies that followed patients with IBD in remission at baseline and had at least 2 consecutive FC measurements with a test interval of 2 weeks to 6 months. Methodological assessment was based on the second Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Results: A total of 1719 articles were identified; 193 were retrieved for full text review. Six studies met eligibility for inclusion. The time interval between FC tests varied between 1 and 3 months. Asymptomatic patients with IBD who had repeated FC measurements above the study's cutoff level had a 53% to 83% probability of developing disease relapse within the next 2 to 3 months. Patients with repeated normal FC values had a 67% to 94% probability to remain in remission in the next 2 to 3 months. The ideal FC cutoff for monitoring could not be identified because of the limited number studies meeting inclusion criteria and heterogeneity between selected studies. Conclusions: Two consecutively elevated FC values are highly associated with disease relapse, indicating a consideration to proactively optimize IBD therapy plans. More prospective data are necessary to assess whether FC monitoring improves health outcomes
Regulatory T Cells Facilitate Thymic Recovery After HSCT by Directly Enhancing Immigration of Donor Derived Thymic Progenitors
BACKGROUND & AIMS: An increasing number of physicians use repeated measurements of stool calprotectin to monitor intestinal inflammation in patients with inflammatory bowel diseases (IBDs). A lateral flow-based rapid test allows patients to measure their own stool calprotectin values at home. The test comes with a software application (IBDoc; Buhlmann Laboratories AG, Schonenbuch, Switzerland) that turns a smartphone camera into a results reader. We compared results from this method with those from the hospital-based reader (Quantum Blue; Buhlmann Laboratories AG) and enzyme-linked immunosorbent assay (ELISA) analysis. METHODS: In a single-center comparison study, we asked 101 participants (10 years of age or older) in the Netherlands to perform the IBDoc measurement on stool samples collected at home, from June 2015 to October 2016. Participants then sent the residual extraction fluid and a fresh specimen from the same bowel movement to our pediatric and adult IBD center at the University Medical Center Groningen, where the level of calprotectin was measured by the Quantum Blue reader and ELISA analysis, respectively. The primary outcome was the agreement of results between IBDoc and the Quantum Blue and ELISA analyses, determined by Bland-Altman plot analysis. RESULTS: We received 152 IBDoc results, 138 samples of residual extraction fluid for Quantum Blue analysis, and 170 fresh stool samples for ELISA analysis. Spearman's rank correlation coefficient was 0.94 for results obtained by IBDoc vs Quantum Blue and 0.85 for results obtained by IBDoc vs ELISA. At the low range of calprotectin level (= 100 mu g/g), and 71% of IBDoc-ELISA results were in agreement. At the high range of calprotectin level (>= 500 mu g/g), 81% of IBDoc-Quantum Blue results were within the predefined limits of agreement (+/- 200 mu g/g) and 64% of IBDoc-ELISA results were in agreement. CONCLUSIONS: Measurements of fecal levels of calprotectin made with home-based lateral flow method were in agreement with measurements made by Quantum Blue and ELISA, as long as concentrations wer
Time-to-reach Target Calprotectin Level in Newly Diagnosed Patients With Inflammatory Bowel Disease
OBJECTIVES: Treatment targets in inflammatory bowel disease (IBD) move away from controlling symptoms towards complete recovery of the intestinal mucosa. Currently, the most frequently used noninvasive surrogate marker of mucosal healing is a faecal calprotectin concentration in the target range. This study tested if there was a relation between time-to-reach target calprotectin and first flare. METHODS: We prospectively included new-onset IBD patients aged 17 and younger in a cloud-based registry (FastForwardCare) and followed them for at least 52 weeks. They were treated according to Dutch national guidelines that advocate a step-up approach. Time-to-reach target was defined as the first calprotectin measurement below 250 μg/g after the start of induction therapy. Time-to-first-flare was the time from the first calprotectin measurement below 250 μg/g until reappearance of symptoms with calprotectin values above 250 μg/g. RESULTS: We included 76 patients (luminal Crohn's disease (CD) 43); ulcerative colitis (UC) 33). Median age at diagnosis was respectively 14.5 and 14.1 years. Median time-to-reach target calprotectin was 37 weeks in CD and 11 weeks in UC patients (Log-rank test, p=0.001). Once the calprotectin target was reached, time-to-first flare was significantly longer in CD than in UC patients (Log-rank test, p=0.001). CD patients with time-to-reach target calprotectin ≤12 weeks after conventional induction therapy (i.e. exclusive enteral nutrition or steroids) had a more favourable disease course in the first year than those with time-to-reach target calprotectin >12 weeks (Log-rank test, p=0.057). In UC patients time-to-reach target calprotectin ≤12 weeks is not associated with a favourable disease course in the first year. CONCLUSIONS: The findings of this prospective registry suggest that a quick response to conventional therapy predicts a favourable disease course in new-onset paediatric CD, but not in UC. The concept "time-to-reach target calprotectin level" rationalizes the indefinite term "response to treatment" and is well suited for studying treatment effectiveness in real-world practices
Reference values of fecal calgranulin C (S100A12) in school aged children and adolescents
Background: Calgranulin C (S100A12) is an emerging marker of inflammation. It is exclusively released by activated neutrophils which makes this marker potentially more specific for inflammatory bowel disease (IBD) compared to established stool markers including calprotectin and lactoferrin. We aimed to establish a reference value for S100A12 in healthy children and investigated whether S100A12 levels can discriminate children with IBD from healthy controls. Methods: In a prospective community-based reference interval study we collected 122 stool samples from healthy children aged 5-19 years. Additionally, feces samples of 41 children with suspected IBD (who were later confirmed by endoscopy to have IBD) were collected. Levels of S100A12 were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) (Inflamark (R)). The limit of detection was 0.22 mu g/g. Results: The upper reference limit in healthy children was 0.75 mu g/g (90% confidence interval: 0.30-1.40). Median S100A12 levels were significantly higher in patients with IBD (8.00 mu g/g [interquartile range (IQR) 2.5-11.6] compared to healthy controls [0.22 mu g/g (IQR <0.22); p <0.001]). The best cutoff point based on receiver operating characteristic curve was 0.33 mu g/g (sensitivity 93%; specificity 97%). Conclusions: Children and teenagers with newly diagnosed IBD have significantly higher S100A12 results compared to healthy individuals. We demonstrate that fecal S100A12 shows diagnostic promise under ideal testing conditions. Future studies need to address whether S100A12 can discriminate children with IBD from nonorganic disease in a prospective cohort with chronic gastrointestinal complaints, and how S100A12 performs in comparison with established stool markers
Effectiveness of three commonly used transition phase diets in the inpatient management of children with severe acute malnutrition: a pilot randomized controlled trial in Malawi.
BACKGROUND: The case fatality rate of severely malnourished children during inpatient treatment is high and mortality is often associated with diarrhea. As intestinal carbohydrate absorption is impaired in severe acute malnutrition (SAM), differences in dietary formulations during nutritional rehabilitation could lead to the development of osmotic diarrhea and subsequently hypovolemia and death. We compared three dietary strategies commonly used during the transition of severely malnourished children to higher caloric feeds, i.e., F100 milk (F100), Ready-to-Use Therapeutic Food (RUTF) and RUTF supplemented with F75 milk (RUTF + F75). METHODS: In this open-label pilot randomized controlled trial, 74 Malawian children with SAM aged 6-60 months, were assigned to either F100, RUTF or RUTF + F75. Our primary endpoint was the presence of low fecal pH (pH ? 5.5) measured in stool collected 3 days after the transition phase diets were introduced. Secondary outcomes were duration of hospital stay, diarrhea and other clinical outcomes. Chi-square test, two-way analysis of variance and logistic regression were conducted and, when appropriate, age, sex and initial weight for height Z-scores were included as covariates. RESULTS: The proportion of children with acidic stool (pH ?5.5) did not significantly differ between groups before discharge with 30, 33 and 23% for F100, RUTF and RUTF + F75, respectively. Mean duration of stay after transitioning was 7.0 days (SD 3.4) with no differences between the three feeding strategies. Diarrhea was present upon admission in 33% of patients and was significantly higher (48%) during the transition phase (p < 0.05). There was no significant difference in mortality (n = 6) between diets during the transition phase nor were there any differences in other secondary outcomes. CONCLUSIONS: This pilot trial does not demonstrate that a particular transition phase diet is significantly better or worse since biochemical and clinical outcomes in children with SAM did not differ. However, larger and more tightly controlled efficacy studies are needed to confirm these findings. TRIAL REGISTRATION: ISRCTN13916953 Registered: 14 January 2013
- …