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Combination of Biological Agents in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Case Series and Review of the Literature.
Olbjørn, C, Rove, JB, Jahnsen, J
Paediatric drugs. 2020;(4):409-416
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Abstract
BACKGROUND Treatment with biological agents such as anti-tumor necrosis factors (TNFs) has become standard of care in moderate to severe pediatric inflammatory bowel disease (IBD). However, a significant proportion of patients experience loss of response to anti-TNFs, need treatment escalation, or develop side effects. There is no data in the literature regarding combination of biological agents in pediatric IBD. METHODS At our hospital, which is a tertiary referral center, we have combined the anti-TNF infliximab with either vedolizumab or ustekinumab in patients with severe pediatric IBD. The indications for dual biological therapy were insufficient efficacy of infliximab or vedolizumab monotherapy, or side effects such as psoriasis due to anti-TNFs. RESULTS Eight patients (four boys) aged 14-17.5 years received a combination of infliximab and vedolizumab due to only a partial response to infliximab, four with Crohn's disease (CD) and four with ulcerative colitis (UC). Clinical remission was achieved in four patients (3 UC) and four had a colectomy (3 CD, 1 UC). Five CD patients (3 girls) aged 11-17 years, on maintenance therapy with infliximab, developed psoriasis resistant to topical treatment. A combination of infliximab and ustekinumab resulted in clinical remission of CD without skin symptoms. No serious adverse events occurred in any of the patients on combination therapy. Thirteen publications report on combining biologicals, all in adult IBD. CONCLUSION In pediatric IBD, combining biological agents seems to be safe and beneficial in selected patients. The safety should be addressed in long-term follow-up studies.
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ORAL AND ENTERAL NUTRITION THERAPY IN INFLAMMATORY BOWEL DISEASES AMONG THE PEDIATRIC POPULATION: A LITERATURE REVIEW.
Souza, GN, Draghi, PF, Yonamine, GH
Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo. 2020;:e2019032
Abstract
OBJECTIVES To review the literature on oral and enteral nutrition therapy and investigate the evidence of its efficacy as a treatment, as well as in preventing relapses and reducing symptoms of inflammatory bowel diseases in the pediatric population. DATA SOURCE We performed a bibliographic search in the PubMed, Web of Science, and Latin American and Caribbean Health Sciences Literature (Literatura Latino-Americana e do Caribe em Ciências da Saúde - Lilacs) databases, using the keywords "inflammatory bowel disease," "diet," and "diet therapy" in English and Portuguese, with filters for pediatric studies published in the previous five years. DATA SUMMARY We selected 16 articles for this study, nine on exclusive and/or partial enteral nutrition and seven on modified oral diets, such as the specific carbohydrate diet (SCD) and the Crohn's Disease exclusion diet (CDED). The studies found evaluated the anthropometric profile of patients and the inflammatory profile of diseases in children before and after the introduction of each specific nutrition therapy. All interventions presented positive changes in these parameters; however, the results were inconclusive regarding the efficacy of SCD and CDED in the treatment and prevention of relapses. CONCLUSIONS Exclusive enteral nutrition has proven to be effective in inducing remission of Crohn's Disease, and the use of partial enteral nutrition for maintenance treatment has shown promising results. Other modified oral diets are inconclusive concerning their effectiveness, requiring further randomized controlled clinical trials.
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A modern multidisciplinary approach to the treatment of enterocutaneous fistulas in Crohn's disease patients.
Papa, A, Lopetuso, LR, Minordi, LM, Di Veronica, A, Neri, M, Rapaccini, G, Gasbarrini, A, Papa, V
Expert review of gastroenterology & hepatology. 2020;(9):857-865
Abstract
INTRODUCTION Enterocutaneous fistulas (ECFs) is a manifestation of penetrating Crohn's disease (CD) that is challenging to treat and has considerable morbidity and mortality rates. AREAS COVERED This review aims to explore the practical and updated principles for the optimal treatment of ECFs in CD patients. EXPERT OPINION Optimal ECF management requires a multidisciplinary approach. Treatment first includes fluid resuscitation and electrolyte rebalancing with control of sepsis by means of antibiotics and, when indicated, drainage of infected collections. Subsequent therapeutic steps include nutritional support, control of the fistula output and treatment of peristomal skin. Anti-TNF-α therapy seems to have limited utility only after sepsis is resolved and intestinal stenosis excluded. However, ECFs heal in only approximately one-third of cases without surgical intervention. Thus, correct surgical timing combined with adequate nutritional support, sepsis resolution and skin care is considered the appropriate preoperative setting.
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The fate of myofibroblasts during the development of fibrosis in Crohn's disease.
Li, C, Kuemmerle, JF
Journal of digestive diseases. 2020;(6):326-331
Abstract
Intestinal fibrosis is a devastating complication in patients with inflammatory bowel disease. Its characteristics include the loss of regular peristalsis and nutrition absorption, excessive deposition of extracellular matrix (ECM) components, thickness of intestinal lumen due to the formation of strictures and of scar tissue. As a major cell type involved in fibrogenesis, the myofibroblasts have already been shown to have a plastic and heterogeneous function in producing abundant collagen, fibronectin and connective tissue growth factor. The primary sources of ECM-producing and vimentin-positive myofibroblasts come from different precursor cells, including bone marrow-derived mesenchymal cells, fibrocytes, pericytes, epithelial to mesenchymal transition and endothelial to mesenchymal transition. Recent immunological research findings suggest that numerous cytokines and chemokines made from macrophages, in addition to T cells and other myeloid cell types, are also important drivers of myofibroblast differentiation and hence of the activation of myofibroblast-mediated transforming growth factor and collagen production. In this review we discuss the origins, roles and cell signaling of myofibroblasts during the development of fibrosis in different organs, particularly in Crohn's disease. Finally, we suggest that the epigenetic and immunological regulation of myofibroblast differentiation may provide a novel antifibrotic strategy in the near future.
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Anemia and iron deficiency in Crohn's disease.
Yueying, C, Yu Fan, W, Jun, S
Expert review of gastroenterology & hepatology. 2020;(3):155-162
Abstract
Introduction: Anemia is a common extraintestinal complication of Crohn's disease (CD) mainly caused by iron deficiency, that affects the quality of life in CD patients. Elucidation of the etiology and pathology of iron-deficiency anemia (IDA) and anemia of chronic diseases (ACD) has developed in recent years. Common biochemical parameters of iron status are insufficient for assessment of patients with anemia and CD. Thus, novel iron indices are required for accurate assessment in IDA patients with CD. Oral iron supplementation for IDA treatment is common and is associated with minor gastrointestinal side effects. Intravenous substitution improves safety profiles but may be not tolerable in some patients. Fortunately, additional therapies for anemia of active CD have emerged in recent years.Area covered: Here, we propose the review article on the link among anemia, iron deficiency, and Crohn's disease. We discuss the current diagnosis and therapy of anemia and iron deficiency in CD and propose the new directions for future research.Expert commentary: Exploring pathogeneses and treatments of anemia and iron deficiency in Crohn's disease will develop potential tools for early diagnosis and effective treatment of anemia in CD patients, and improve their life quality.
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Cannabis for the Treatment of Crohn's Disease and Ulcerative Colitis: Evidence From Cochrane Reviews.
Kafil, TS, Nguyen, TM, MacDonald, JK, Chande, N
Inflammatory bowel diseases. 2020;(4):502-509
Abstract
BACKGROUND We systematically reviewed the safety and effectiveness of cannabis and cannabinoids treatment for Crohn's disease (CD) and ulcerative colitis (UC). METHODS MEDLINE, Embase, WHO ICTRP, AMED, PsychINFO, CENTRAL, ClinicalTrials.Gov, and the European Clinical Trials Register were searched for relevant studies. MAIN RESULTS Five randomized controlled trials (3 CD and 2 UC studies, 185 participants) were included. One CD study (N = 21) showed 45% (5 of 11) of the cannabis cigarette group experienced clinical remission compared with 10% (1 of 10) of the placebo group (risk ratio [RR] 4.55; 95% CI, 0.63-32.56). Another CD study (N = 19) did not show significant rates of clinical remission. Forty percent (4 of 10) of participants in the cannabis oil group experienced remission compared with 33% (3 of 9) of the placebo group (RR 1.20; 95% CI, 0.36-3.97). A UC study (N = 60) did not have significant clinical remission rates. Twenty-four percent (7 of 29) of cannabis oil participants experienced remission compared with 26% (8 of 31) of placebo participants (RR 0.94; 95% CI, 0.39-2.25). A second UC study (N = 32) showed the effects on disease activity, C-reactive protein levels, and fecal calprotectin levels were uncertain. Adverse events were more prevalent in the cannabis groups for both CD and UC studies. GRADE analysis for the UC and CD studies ranged from very low to moderate. CONCLUSIONS In summary, no firm conclusions can be made regarding the safety and effectiveness of cannabis and cannabinoids in adults with CD and UC.
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Dietary Strategies for Maintenance of Clinical Remission in Inflammatory Bowel Diseases: Are We There Yet?
Gkikas, K, Gerasimidis, K, Milling, S, Ijaz, UZ, Hansen, R, Russell, RK
Nutrients. 2020;(7)
Abstract
The etiopathogenesis of Inflammatory bowel disease (IBD) is a result of a complex interaction between host immune response, the gut microbiome and environmental factors, such as diet. Although scientific advances, with the use of biological medications, have revolutionized IBD treatment, the challenge for maintaining clinical remission and delaying clinical relapse is still present. As exclusive enteral nutrition has become a well-established treatment for the induction of remission in pediatric Crohn's disease, the scientific interest regarding diet in IBD is now focused on the development of follow-on dietary strategies, which aim to suppress colonic inflammation and delay a disease flare. The objective of this review is to present an extensive overview of the dietary strategies, which have been used in the literature to maintain clinical remission in both Crohn's disease and Ulcerative colitis, and the evidence surrounding the association of dietary components with clinical relapse. We also aim to provide study-related recommendations to be encompassed in future research studies aiming to investigate the role of diet during remission periods in IBD.
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The Rundown of Dietary Supplements and Their Effects on Inflammatory Bowel Disease-A Review.
Malinowski, B, Wiciński, M, Sokołowska, MM, Hill, NA, Szambelan, M
Nutrients. 2020;(5)
Abstract
Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are a life-long, chronic, and relapsing problem affecting 11.2 million people worldwide. To date, there is pharmacological therapy to treat symptoms such as diarrhea, constipation, and abdominal cramping/pain. These medications also help to alleviate everyday discomfort; however, there are no curative therapies. Recent studies have investigated the combination of pharmacological treatment along with nutritional interventions to improve quality of life and risk of disease relapse. Dietary supplements, specifically probiotics, polyphenols, fibers, fatty acids and low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diets (FODMAP diets), have been closely looked at to determine their effect, if any, on the development of inflammatory bowel disease and its course of progression. Approximately 30 studies were carefully reviewed and analyzed to appreciate the value of these above-mentioned supplements and their influence on this gastrointestinal disease. After analysis, it has been demonstrated that by implementing fibers, polyphenols, and fatty acids, as well as keeping a low-saccharide diet for those patients with Crohn's disease and ulcerative colitis can improve quality of life and invoke clinical remission. Some polyphenols, specifically curcumin and resveratrol, have proved to decrease disease activity in studies reviewed. Although these studies have become a topic of recent interest, it would be of great value to doctors and patients alike, to continue in this direction of research and to improve the findings for best treatment substances and dosages. This would lead to increased quality of life and disease control leading to fewer complications in the future.
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Pancreatic exocrine insufficiency and Crohn's disease.
Hedström, A, Steiner, C, Valente, R, Haas, SL, Löhr, JM, Vujasinovic, M
Minerva gastroenterologica e dietologica. 2020;(1):17-22
Abstract
BACKGROUND According to the European evidence-based consensus, published by European Crohn's and Colitis Organization (ECCO), diseases of the pancreas are included as extra-intestinal manifestations in IBD in the forms of acute pancreatitis (AP), chronic pancreatitis (CP), autoimmune pancreatitis (AIP), pancreatic duct abnormalities and pancreatic exocrine insufficiency (PEI). Presence of pancreatic autoantibodies directed against the exocrine of the pancreas has been reported in about one-third of CD. However, association between CD and PEI is not fully elucidated. METHODS Patients with a diagnosis of CD were recruited at the Department for Digestive Diseases at Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Fecal elastase-1 (FE-1) measurements were performed using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS There were 20 patients included in the study, 13 (65%) males and 7 (35%) females, mean age 48.3±1.4 years (range 29-67 years). Mean duration of CD was 15.7±2.1 years (range 1-40 years). There were 11 (55%) patients without history of bowel surgery and 9 (45%) patients after ileocecal resection. FE-1 test was normal in all patients, among them 15 (75%) patients with the values of FE-1>500. CONCLUSIONS Fecal elastase-1 level was normal in all patients with CD strongly indicated absence of PEI in this group of patients.
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Diet Advice for Crohn's Disease: FODMAP and Beyond.
Popa, SL, Pop, C, Dumitrascu, DL
Nutrients. 2020;(12)
Abstract
Crohn's disease (CD) is a chronic, progressive, and destructive granulomatous inflammatory bowel disorder that can involve any part of the gastrointestinal tract. It has been presumed that different types of diet might improve gastrointestinal symptoms in CD patients. The aim of this review was to clarify the efficiency and indications of a low-"fermentable oligo-, di-, mono-saccharides and polyols" (FODMAP) diet (LFD) in CD and to further analyze the available data on other types of diets. PubMed, Cochrane Library, EMBASE and WILEY databases were screened for relevant publications regarding the effect of FODMAP diets on CD. Our search identified 12 articles analyzing the effect of an LFD in CD, 5 articles analyzing the effect of a Mediterranean diet (MD), 2 articles analyzing the effect of a vegetarian diet (VD), and 2 articles analyzing the effect of a low-lactose diet (LLD). The majority of the studies included in this review show the significant efficiency of the LFD in CD patients. We found significant evidence demonstrating that the LFD has a favorable impact on gastrointestinal symptoms in CD patients. Notwithstanding the evidence, it remains to be established if an LFD is more efficient than other types of diets in the short term and especially in the long term.