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Management of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care-An Evidence-based Guideline From European Crohn’s and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition

Dan Turner 1Frank M Ruemmele 2Esther Orlanski-Meyer 1Anne M Griffiths 3Javier Martin de Carpi  et al. J Pediatr Gastroenterol Nutr. 2018 Aug;67(2):257-291. doi: 10.1097/MPG.0000000000002035.

Background: The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. Methods: These guidelines are a joint effort of the European Crohn’s and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before 2 face-to-face meetings. All 40 included recommendations and 86 practice points were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate. Results: These guidelines discuss how to optimize the use of mesalamine (including topical), systemic and locally active steroids, thiopurines and, for more severe disease, biologics. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision-making based on clinical assessment and the Paediatric UC Activity Index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology, and transition. A brief section on disease classification using the PIBD-classes criteria and IBD-unclassified is also part of these guidelines. Conclusions: These guidelines provide a guide to clinicians managing children with UC and IBD-unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.

https://pubmed.ncbi.nlm.nih.gov/30044357/

https://www.zora.uzh.ch/id/eprint/165387/

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Pediatric inflammatory bowel disease : clinical and immunological aspects on remission treatment

Finally, we studied the immunological profile in blood at onset and in intestinal mucosa at onset and after GMA and EEN treatment. We conclude that an active approach is needed in the care of children with IBD to achieve and maintain remission. Our findings reveal that the children on IFX maintenance treatment were only in remission in 28% of the visits. The combination of GMA and mesalazine was found to be a safe and effective treatment in children with newly onset IBD. It seems plausible to speculate that the decreases in mucosal cytokines after the induction of remission may explain the good clinical result. Moreover, a change in the mucosal cytokine profile after induction of remission with EEN was observed. By investigating the chemokine receptors, we found a possible prognostic IBD marker, and by analyzing the cytokine profiles in mucosal biopsies, we have extended the knowledge of immunological phenotypes in children with IBD. Suggestions for the future Corticosteroid-free treatment alternatives must be explored and those currently in use must be optimized. To conclude, more and bigger studies are needed to explore the pathogenesis of IBD to determine new treatment alternatives.

https://www.semanticscholar.org/paper/Pediatric-inflammatory-bowel-disease-%3A-clinical-and-Rolandsdotter/e3d901c2c80db622f6cfbf92b03ee403b6e4a9b6#paper-header

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Granulocitoaféresis en 2017. Puesta al día (Spanish)

Cabriada, J.L.Rodríguez-Lago, I.

Enfermedad Inflamatoria Intestinal 20017 (16) 2, 62-69 DOI: 10.1016/j.eii.2016.12.001 

Granulocyte apheresis is a procedure that allows the removal of different activated leukocyte populations and it also modifies some circulating inflammatory mediators. These effects, along with its immunomodulatory potential, make it an attractive therapeutic option in inflammatory bowel disease. Previous studies with this technique have had significant limitations, but recent data is emerging about the ideal clinical setting in which granulocyte apheresis should be indicated. Most of the evidence supports its use in conditions that are dependent or refractory to corticosteroids, especially when treatments with immunomodulators or biologics has failed and when it is necessary to reduce or avoid the use of systemic corticosteroids. Its excellent safety profile gives it a role in cases of comorbidity or risk in the use of immunosuppressive drugs or in paediatric patients. In this review, we provide an update on the role of granulocyte apheresis in inflammatory bowel disease.

https://www.elsevier.es/es-revista-enfermedad-inflamatoria-intestinal-al-dia-220-articulo-granulocitoaferesis-2017-puesta-al-dia-S1696780116300999

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Leukocytapheresis in pediatric patients with ulcerative colitis

Takeshi Tomomasa 1Hitoshi TajiriSeiichi KagimotoToshiaki ShimizuAtsushi YodenKosuke UshijimaKeiichi UchidaHiroaki KanekoDaiki AbukawaMutsuko KonnoShun-ichi MaisawaTakao KohsakaAkio KobayashiJapanese Study Group for Pediatric Ulcerative Colitis. J Pediatr Gastroenterol Nutr. 2011 Jul;53(1):34-9. doi: 10.1097/MPG.0b013e31821058bc.

Objective: Leukocytapheresis (LCAP) is a nonpharmacologic therapy that has recently been used to treat ulcerative colitis (UC). This multicenter open-label study prospectively assessed the efficacy and safety of LCAP in pediatric patients with UC. Patients and methods: Twenty-three patients ages 8 to 16 years with moderate (n = 19) to severe (n = 4) steroid-resistant UC were enrolled. One of 2 LCAP columns with different volumes (model EX and the half-volume model EI) was selected, according to body weight. LCAP was performed once per week for 5 consecutive weeks. Clinical and laboratory data were collected at predetermined time points. The primary endpoint was decreased stool frequency/hematochezia score, and secondary endpoints were clinical, laboratory, and endoscopic improvements. Results: The stool frequency/hematochezia score decreased significantly from 4.5 ± 1.2 before treatment to 1.6 ± 1.9 after the fifth treatment. Clinical parameters, including stool frequency, presence of visible blood, abdominal pain, and body temperature, were significantly improved. Fecal calprotectin decreased significantly. Endoscopic findings evaluated using Matts score also improved (P < 0.01). The steroid dose decreased from 1.1 ± 0.4 mg/kg before treatment to 0.8 ± 0.5 mg/kg after treatment. There were no significant differences in changes between the EX and EI columns. The incidence of adverse effects was 61%, although none was serious. The most common adverse effects were decreased hematocrit and hemoglobin concentration. Conclusions: The present study showed that LCAP was well tolerated in children with UC, mostly moderate, and was as effective as in adults. The types of pediatric patients best suited to LCAP remain to be determined.

https://pubmed.ncbi.nlm.nih.gov/21694533/

Leukocytapheresis in Pediatric Patients With Ulcerative Coli… : Journal of Pediatric Gastroenterology and Nutrition (lww.com)

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Leukocytapheresis in pediatric patients with ulcerative colitis

Takeshi Tomomasa 1Hitoshi TajiriSeiichi KagimotoToshiaki ShimizuAtsushi YodenKosuke UshijimaKeiichi UchidaHiroaki KanekoDaiki AbukawaMutsuko KonnoShun-ichi MaisawaTakao KohsakaAkio KobayashiJapanese Study Group for Pediatric Ulcerative Colitis J Pediatr Gastroenterol Nutr. 2011 Jul;53(1):34-9. doi: 10.1097/MPG.0b013e31821058bc.

Objective: Leukocytapheresis (LCAP) is a nonpharmacologic therapy that has recently been used to treat ulcerative colitis (UC). This multicenter open-label study prospectively assessed the efficacy and safety of LCAP in pediatric patients with UC. Patients and methods: Twenty-three patients ages 8 to 16 years with moderate (n = 19) to severe (n = 4) steroid-resistant UC were enrolled. One of 2 LCAP columns with different volumes (model EX and the half-volume model EI) was selected, according to body weight. LCAP was performed once per week for 5 consecutive weeks. Clinical and laboratory data were collected at predetermined time points. The primary endpoint was decreased stool frequency/hematochezia score, and secondary endpoints were clinical, laboratory, and endoscopic improvements. Results: The stool frequency/hematochezia score decreased significantly from 4.5 ± 1.2 before treatment to 1.6 ± 1.9 after the fifth treatment. Clinical parameters, including stool frequency, presence of visible blood, abdominal pain, and body temperature, were significantly improved. Fecal calprotectin decreased significantly. Endoscopic findings evaluated using Matts score also improved (P < 0.01). The steroid dose decreased from 1.1 ± 0.4 mg/kg before treatment to 0.8 ± 0.5 mg/kg after treatment. There were no significant differences in changes between the EX and EI columns. The incidence of adverse effects was 61%, although none was serious. The most common adverse effects were decreased hematocrit and hemoglobin concentration. Conclusions: The present study showed that LCAP was well tolerated in children with UC, mostly moderate, and was as effective as in adults. The types of pediatric patients best suited to LCAP remain to be determined.

https://pubmed.ncbi.nlm.nih.gov/21694533/

https://journals.lww.com/jpgn/Fulltext/2011/07000/Leukocytapheresis_in_Pediatric_Patients_With.5.aspx

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Leukocytapheresis in a girl with severe ulcerative colitis refractory to corticosteroids, infliximab, and cyclosporine A

Katalin DittrichMarkus RichterWolfgang RascherHenrik Köhler Inflamm Bowel Dis 2008 Oct;14(10):1466-7. doi: 10.1002/ibd.20464.

Although medical therapy remains the first-line treatment for UC, colectomy may be required for patients with severe medically refractory disease. Leukocytapheresis (LCAP) has been reported as a new line of therapy in
patients with UC. Only 2 pediatric case series, not including patients on immunosuppressive therapy or biologicals, treated with granulocytapheresis have been reported. The patient reported by us is the youngest to the best of our knowledge in which this LCAP technique was used . She had severe colitis refractory to corticosteroids, infliximab and yclosporine A. We were able to avoid colectomy and the procedure was well tolerated.

https://pubmed.ncbi.nlm.nih.gov/18421764/

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Efficacy of Granulocyte Apheresis in Pediatric Patients With Ulcerative Colitis: A Pilot Study

Ikeda, Hitoshi; Ishimaru, Yuki; Takayasu, Hajime; Fujino, Junko; Kisaki, Yoshiyuki; Otani, Yushi; Yamagishi, Junko; Tahara, Kazunori. J Pediatr Gastroenterol Nutr 2006; 43:592-6. doi: 10.1097/01.mpg.0000237928.07729.79

Objectives: Granulocyte apheresis (GCAP), involving the removal of granulocytes from the blood, may improve clinical symptoms and facilitate a reduction in the dose of steroids in adult patients with ulcerative colitis. As a preliminary trial, GCAP was used to taper the dose of steroids in 4 pediatric patients with ulcerative colitis. Methods: Three males and 1 female ranging from 11 to 17 years old were treated with GCAP once per week for 5 consecutive weeks/course. The ages of patients at clinical onset ranged from 8 to 12 years and the length of time from the clinical onset to GCAP treatment ranged from 28 to 58 months (median, 38.5 months). Results: In 2 patients, symptoms and signs indicating disease activity improved after 2 courses of GCAP. Laboratory data and endoscopic findings also improved after treatment and the clinical efficacy was judged to be excellent in these patients. In 1 patient, GCAP improved laboratory and endoscopic hallmarks, but bloody stools persisted. Finally, the treatment was ineffective in the fourth patient who eventually underwent surgery. Conclusions: GCAP is effective in improving clinical symptoms and may play an important role in converting steroid therapy to other treatments in children with steroid-refractory or steroid-dependent ulcerative colitis.

https://journals.lww.com/jpgn/FullText/2006/11000/Efficacy_of_Granulocyte_Apheresis_in_Pediatric.8.aspx

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Treating ulcerative colitis without medications “Look Mom, no drugs!”

Russell D. Cohen

Gastroenterology2005 Vol. 128; Iss. 1 DOI:10.1053/j.gastro.2004.11.024

Clinical response rates in uncontrolled inflammatory bowel disease studies have commonly run in the 30%–50% range; as a result, early uncontrolled trials need validation from adequately blinded randomized trials before widespread application of such novel therapies. Although the long-term maintenance data from this study (60% at 8 months) is encouraging, further studies of the optimal interval for repeating apheresis for reinduction of remission or maintenance arealso in order. The potential for apheresis-based therapies as either a stand-alone strategy or in combination with other proven therapies in
the treatment of inflammatory bowel diseases also needs to be further elucidated. The promise of “no medications” for effective therapy in the treatment of ulcerative colitis is enticing, and perhaps a step closer, but clearly needs to be substantiated by larger controlled trials.

https://booksc.eu/book/20696837/914ad3

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Leukocytapheresis with leukocyte removal filter for severe ulcerative colitis in childhood

Yukihiko Kawasaki 1Junzo SuzukiShigeo SuzukiHitoshi Suzuki

J Pediatr Gastroenterol Nutr. 2004 Oct;39(4):422-5. doi: 10.1097/00005176-200410000-00021.

Generally, UC is associated with intervals of acute exacerbation and the administration of corticosteroids is effective in bringing about a clinical remission (1). Corticosteroids are not always effective even in doses over 1 mg/kg/day. In addition, the long-term use of corticosteroids often causes serious side effects such as growth retardation, glaucoma, hormonal disturbance, peptic ulcer, liver dysfunction and psychologic problems. Alternative treatment for active UC may be necessary to avoid the clinical problems associated with corticosteroid therapy. In recent years, leukocytapheresis (LCAP) and granulocytapheresis (GCAP) using a leukocyte removal filter has been found effective in some cases of adults with inflammatory bowel disease (2,3). However, there have been few reports concerning the efficacy of LCAP and GCAP for UC in childhood (4).We report two children with severe steroid-dependent UC in whom LCAP with leukocyte removal filter was used in treatment. LCAP therapy was safe and effective in two children with refractory UC and allowed discontinuation of corticosteroid therapy with an improvement in quality of life. Prospective studies of this therapy will be needed to clarify the role of LCAP in treatment of childhood UC.

https://pubmed.ncbi.nlm.nih.gov/15448435/

https://journals.lww.com/jpgn/Fulltext/2004/10000/Leukocytapheresis_with_Leukocyte_Removal_Filter.21.aspx

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Cytapheresis therapy for ulcerative colitis in three pediatric patients

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