ABSTRACT
PURPOSE: Childhood stricturing Crohn's disease (CD) has significant morbidity. Interventions including resection, stricturoplasty and endoscopic balloon dilatation (EBD) are often required. Optimal intervention modality and timing, and use of adjuvant medical therapies, remains unclear. We aim to review the therapies used in paediatric stricturing CD. METHODS: A systematic review in accordance with PRISMA was performed (PROSPERO: CRD42020164464). Demographics, stricture features, interventions and outcomes were extracted. RESULTS: Fourteen studies were selected, including 177 patients (183 strictures). Strictures presented at 40.6 months (range 14-108) following CD diagnosis. Medical therapy was used in 142 patients for an average of 20.4 months (2-36), with a complete response in 11 (8%). Interventions were undertaken in 138 patients: 53 (38%) resections, 39 (28%) stricturoplasties, and 17 (12%) EBD. Complications occurred in 11% of resections, versus 15% stricturoplasties, versus 6% EBD (p = 0.223). At a median follow-up of 1.9 years (interquartile range 1.2-2.4) pooled stricture recurrence was 22%. Resection had 9% recurrence, versus 38% stricturoplasty, versus 47% EBD (p < 0.001). CONCLUSIONS: Resection is associated with a low incidence of recurrence and complications. There remains a paucity of evidence regarding adjuvant medical therapy and the role of EBD. We propose a minimum reported dataset for interventions in paediatric stricturing CD.
Subject(s)
Crohn Disease/therapy , Endoscopy, Gastrointestinal , Adolescent , Catheterization , Child , Child, Preschool , Constriction, Pathologic/complications , Constriction, Pathologic/surgery , Crohn Disease/complications , Dilatation , Endoscopy, Gastrointestinal/adverse effects , Female , Humans , Incidence , Male , Recurrence , Treatment OutcomeABSTRACT
PURPOSE: To generate 3-dimensional (3D) printed ultrasound (US)-compatible vascular models (3DPVAM) and test them for noninferiority in training medical students in femoral artery access. MATERIALS AND METHODS: A 3DPVAM of normal femoral artery (FA) anatomy was developed from an anonymized computerized tomography (CT) examination. Students were randomized to a 3DPVAM or a commercial model (CM) simulation experience (SE) for US-guided FA access. Students completed a pre-SE questionnaire ranking their self-confidence in accessing the artery on a 5-point Likert scale. A standardized SE was administered by interventional radiology faculty or trainees. Students completed a post-SE questionnaire ranking comfort with FA access on a Likert scale. Student questionnaire results from the 3DPVAM group were compared with those from the CM group by using chi-square, Wilcoxon signed-rank, and noninferiority analyses. RESULTS: Twenty-six and twenty-three students were randomized to 3DPVAM and commercial model training, respectively. A total of 76.9% of 3DPVAM trainees and 82.6% of CM trainees did not feel confident performing FA access prior to the SE. In both groups, training increased student confidence by 2 Likert points (3DPVAM: P < 0.001; CM P < 0.001). The confidence increase in 3DPVAM trainees was noninferior to that in CM trainees (P < 0.001). CONCLUSIONS: Generation of a custom-made 3DPVAM is feasible, producing comparable subjective training outcomes to those of CM. Custom-made 3D-printed training models, including incorporation of more complex anatomical configurations, could be used to instruct medical students in procedural skills.
Subject(s)
Catheterization, Peripheral/methods , Education, Medical, Undergraduate/methods , Femoral Artery/diagnostic imaging , Models, Anatomic , Models, Cardiovascular , Printing, Three-Dimensional , Radiography, Interventional/methods , Radiology, Interventional/education , Students, Medical , Clinical Competence , Computed Tomography Angiography , Curriculum , Humans , PuncturesABSTRACT
Background: Pediatric ulcerative colitis (UC) presents at an earlier age and increasing prevalence. Our aim was to examine morbidity, steroid sparing strategies, and surgical outcome in children with active UC. Methods: A national prospective audit was conducted for the inpatient period of all children with UC for medical or surgical treatment in the United Kingdom (UK) over 1 year. Thirty-two participating centers recruited 224 children in 298 admissions, comparisons over 6 years were made with previous audits. Results: Over 6 years, recording of Paediatric Ulcerative Colitis Activity Index (PUCAI) score (median 65)(23% to 55%, P < 0.001), guidelines for acute severe colitis (43% to 77%, P < 0.04), and ileal pouch surgery registration (4% to 56%, P < 0.001) have increased. Corticosteroids were given in 183/298 episodes (61%) with 61/183 (33%) not responding and requiring second line therapy or surgery. Of those treated with anti-TNFalpha (16/61, 26%), 3/16 (18.8%) failed to respond and required colectomy. Prescription of rescue therapy (26% to 49%, P = 0.04) and proportion of anti-TNFalpha (20% to 53%, P = 0.03) had increased, colectomy rate (23.7% to 15%) was not significantly reduced (P = 0.5). Subtotal colectomy was the most common surgery performed (n = 40), and surgical complications from all procedures occurred in 33%. In 215/224 (96%) iron deficiency anemia was detected and in 51% treated, orally (50.2%) or intravenously (49.8%). Conclusions: A third of children were not responsive to steroids, and a quarter of these were treated with anti-TNFalpha. Colectomy was required in 41/298 (13.7%) of all admissions. Our national audit program indicates effectiveness of actions taken to reduce steroid dependency, surgery, and iron deficiency. 10.1093/ibd/izy042_video1izy042.video15769503407001.
Subject(s)
Colectomy/statistics & numerical data , Colitis, Ulcerative/therapy , Immunosuppressive Agents/therapeutic use , Steroids/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adolescent , Child , Child, Preschool , Colectomy/adverse effects , Colitis, Ulcerative/epidemiology , Female , Humans , Male , Prospective Studies , Treatment Outcome , United Kingdom/epidemiologyABSTRACT
OBJECTIVES: The aim of the study was to summarize short-term effectiveness, safety, and cost of using infliximab biosimilar (IFX-B) drugs, (Inflectra [Hospira] and Remsima [NAAP]) compared to originator infliximab (IFX-O) (Remicade [MSD]) in biologic naive pediatric inflammatory bowel disease in the United Kingdom. METHODS: Prospective audit of patients starting anti-tumour necrosis factor (TNF) therapy. Disease severity, response to treatment, and remission rate was measured by Pediatric Crohn's Disease Activity Index (PCDAI) and/or Physician Global Assessment. RESULTS: Between March 2015 and February 2016, 278 patients (175 IFX-O, 82 IFX-B, and 21 Adalimumab) were started on anti-TNF therapy. This was compared with collected data on 398 patients started on IFX-O from 2011 to 2015. At initiation, median PCDAI was 36 (20,48) (nâ=â42) in the IFX-O group and 28 (20,40) (nâ=â29) in the IFX-B group, (Pâ=â0.08). Immunosuppression rates were similar: 150/175 (86%) for IFX-O and 65/82 (79%) for IFX-B (Pâ>â0.05). Post induction, median PCDAI score was 5 (0,11) (nâ=â19) and 0 (0,8) (nâ=â15) in the IFX-O and IFX-B groups, respectively (Pâ=â0.35). There was no difference in response to treatment using Physician Global Assessment 85% (nâ=â28) in IFX-O group and 86% (nâ=â19) in IFX-B group (Pâ>â0.05). Adverse events at initiation and post induction were not different between both groups (Pâ>â0.05). Using conservative calculations, £875,000 would have been saved for a 1-year period with universal adoption of biosimilars in patients who were instead treated with IFX-O. CONCLUSIONS: IFX-B is likely as effective as IFX-O in treating IBD in comparable pediatric populations. Sites should adopt infliximab biosimilar for new starts due to cost reduction with no difference in other parameters.
Subject(s)
Biosimilar Pharmaceuticals/therapeutic use , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Adolescent , Child , Female , Humans , Induction Chemotherapy , Male , Medical Audit , Prospective Studies , Severity of Illness Index , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors , United KingdomABSTRACT
OBJECTIVE: The aim of this study was to measure the effectiveness, safety, and use of anti-tumor necrosis Factor (TNF) therapy in pediatric inflammatory bowel disease in the United Kingdom (UK). METHODS: Prospective UK audit of patients newly starting anti-TNF therapy. Disease severity was assessed using Physician Global Assessment +/or the Paediatric Crohn Disease Activity Index. RESULTS: A total of 37 centers participated (23/25 specialist pediatric inflammatory bowel disease sites). A total of 524 patients were included: 429 with Crohn disease (CD), 76 with ulcerative colitis (UC), and 19 with IBD unclassified (IBDU). Eighty-seven percent (488/562) of anti-TNF was infliximab; commonest indication was active luminal CD 77% (330/429) or chronic refractory UC/IBDU 56% (53/95); 79% (445/562) had concomitant co-immunosuppression. In CD (267/429 male), median time from diagnosis to treatment was 1.42 years (interquartile range 0.63-2.97). Disease (at initiation) was moderate or severe in 91% (156/171) by Physician Global Assessment compared to 41% (88/217) by Paediatric Crohn Disease Activity Index (Kappa (κ) 0.28â=âonly "fair agreement"; Pâ<â0.001.Where documented, 77% (53/69) of patients with CD responded to induction; and 65% (46/71) entered remission. A total of 2287 infusions and 301.96 years of patient' follow-up (nâ=â385) are represented; adverse events affected 3% (49/1587) infliximab and 2% (2/98) adalimumab infusions (no deaths or malignancies). Peri-anal abscess drainage was less common after anti-TNF initiation (CD), that is 26% (27/102) before, 7% (3/42) after (Pâ=â0.01); however, pre and post anti-TNF data collection was not over equal time periods. CONCLUSIONS: Anti-TNFs are effective treatments, usually given with thiopurine co-immunosuppression. This study highlights deficiencies in formal documentation of effect and disparity between disease severity scoring tools, which need to be addressed to improve ongoing patient care.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Gastrointestinal Agents/therapeutic use , Immunosuppression Therapy/methods , Inflammatory Bowel Diseases/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adolescent , Antibodies, Monoclonal, Humanized/adverse effects , Child , Child, Preschool , Clinical Audit , Female , Gastrointestinal Agents/adverse effects , Humans , Immunosuppression Therapy/adverse effects , Infant , Male , Prospective Studies , Remission Induction , Severity of Illness Index , Treatment Outcome , United KingdomABSTRACT
AIMS: Iron deficiency anaemia frequently complicates inflammatory bowel disease (IBD) in children and adults. Oral iron may exacerbate gastrointestinal symptoms and absorption may be insufficient in intestinal inflammation. Even where oral iron is successful, repletion of iron stores can be unacceptably slow. Intravenous iron compounds were in the past associated with serious adverse reactions and historically were considered a last resort in children. New generation preparations have a safer profile in adults, although reluctance to use them in children may persist, where safety data are lacking. We investigate the safety and efficacy of ferric carboxymaltose and iron sucrose in children. METHODS: We retrospectively identified all children with IBD who received parenteral iron over a 38-month period in a single regional referral centre. Safety, tolerability and adverse events were established by case note review. Efficacy was assessed by change in haematinic indices pre- and post-treatment. RESULTS: Forty-one children (18 male; median age 14 years, range 3-17) received a total of 104 iron infusions. Of these, 44% (18) had Crohn's disease; 56% (23) ulcerative colitis. Thirty-five received ferric carboxymaltose, seven iron sucrose and one both. Three children developed mild rash post infusion which resolved quickly with chlorphenamine. Mean increase in haemoglobin was 2.5 g dl-1 (0.3-5.8). Iron levels increased by a mean of 8.4 g dl-1 (1-25), transferrin saturation by 16.2% (2-47). Transferrin decreased by 0.84 g dl-1 (0.3-3.4). CONCLUSIONS: New generation parenteral iron preparations are safe, well tolerated and efficacious in children with iron deficiency anaemia and IBD.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Colitis, Ulcerative/complications , Crohn Disease/complications , Ferric Compounds/administration & dosage , Ferric Oxide, Saccharated/administration & dosage , Maltose/analogs & derivatives , Adolescent , Anemia, Iron-Deficiency/etiology , Child , Child, Preschool , Female , Ferric Compounds/adverse effects , Ferric Oxide, Saccharated/adverse effects , Hemoglobins/metabolism , Humans , Infusions, Intravenous , Male , Maltose/administration & dosage , Maltose/adverse effects , Retrospective Studies , Transferrin/metabolismABSTRACT
The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.
Subject(s)
Colectomy , Crohn Disease/surgery , Intestine, Small/surgery , Perioperative Care/methods , Anastomosis, Surgical , Anti-Inflammatory Agents/therapeutic use , Biological Therapy , Chemotherapy, Adjuvant , Child , Colectomy/methods , Crohn Disease/drug therapy , Elective Surgical Procedures , Humans , Immunosuppressive Agents/therapeutic use , Patient Selection , Postoperative Complications/etiology , Postoperative Complications/therapy , Recurrence , Secondary Prevention/methodsABSTRACT
BACKGROUND AND AIMS: Immunosuppressive therapy for inflammatory bowel disease (IBD) in pediatric patients is thought to increase the risk of malignancy and lymphoproliferative disorders, including hemophagocytic lymphohistiocytosis (HLH). We compared unadjusted incidence rates of malignancy and HLH in pediatric patients with IBD exposed to infliximab (IFX) with patients not exposed to biologics and calculated standardized incidence ratios (SIRs). METHODS: We collected and analyzed data from 5766 participants in a prospective study of long-term outcomes of pediatric patients with IBD (NCT00606346), from May 31, 2007 through June 30, 2016. Patients were 17 years old or younger and had Crohn's disease, ulcerative colitis, or IBD-unclassified with 24,543.0 patient-years of follow-up. We estimated incidence rates for malignancy and HLH as events/1000 patient-years of follow-up. We calculated age-, sex-, and race-adjusted SIRs, with 95% confidence intervals (CIs), using the Surveillance, Epidemiology, and End Results Program (SEER) database. RESULTS: Thirteen of the 15 patients who developed a malignancy and all 5 of the patients who developed HLH had been exposed to thiopurines; 10 patients with malignancy had also been exposed to a biologic agent. Unadjusted incidence rates showed no increased risk of malignancy (0.46/1000 patient-years) or HLH (0.0/1000 patient-years) in patients exposed to IFX as the only biologic vs those unexposed to biologics (malignancy: 1.12/1000 patient-years; HLH: 0.56/1000 patient-years). SIRs did not demonstrate an increased risk of malignancy among patients exposed to IFX (SIR, 1.69; 95% CI, 0.46-4.32) vs patients not exposed to a biologic agent (SIR, 2.17; 95% CI, 0.59-5.56), even when patients were stratified by thiopurine exposure. CONCLUSIONS: In determination of age-, sex-, and race-adjusted SIRs using data from a large clinical study and the SEER database, we found that IFX exposure did not associate with increased risk of malignancy or HLH in pediatric patients with IBD. Thiopurine exposure is an important precedent event for the development of malignancy or HLH in pediatric patients with IBD.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Biological Products/adverse effects , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Gastrointestinal Agents/therapeutic use , Infliximab/adverse effects , Lymphohistiocytosis, Hemophagocytic/epidemiology , Neoplasms/epidemiology , Adolescent , Age Distribution , Anti-Inflammatory Agents/adverse effects , Child , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/immunology , Crohn Disease/diagnosis , Crohn Disease/immunology , Europe/epidemiology , Female , Gastrointestinal Agents/adverse effects , Humans , Immunocompromised Host , Incidence , Lymphohistiocytosis, Hemophagocytic/chemically induced , Lymphohistiocytosis, Hemophagocytic/diagnosis , Male , Neoplasms/chemically induced , Neoplasms/diagnosis , North America/epidemiology , Prospective Studies , Registries , Risk Assessment , Risk Factors , SEER Program , Sex Distribution , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Because of previous concerns about the efficacy and safety of oral iron for treating iron deficiency anaemia in inflammatory bowel disease [IBD], particularly in young people, we compared the effects of ferrous sulphate on haemoglobin response, disease activity and psychometric scores in adolescents and adults with IBD. We also assessed the relation of baseline serum hepcidin to haemoglobin response. METHODS: We undertook a prospective, open-label, 6-week non-inferiority trial of the effects of ferrous sulphate 200 mg twice daily on haemoglobin, iron status, hepcidin, disease activity (Harvey-Bradshaw Index, Simple Colitis Clinical Activity Index, C-reactive protein [CRP]), faecal calprotectin and psychometric scores in 45 adolescents [age 13-18 years] and 43 adults [>18 years]. RESULTS: On intention-to-treat analysis, ferrous sulphate produced similar rises in haemoglobin in adolescents {before treatment 10.3 g/dl [0.18] (mean [SEM]), after 11.7 [0.23]: p < 0.0001} and adults (10.9 g/dl [0.14], 11.9 [0.19]: p < 0.0001); transferrin saturation, ferritin [in adolescents] and hepcidin [in adults] also increased significantly. On per-protocol univariate analysis, the haemoglobin response was inversely related to baseline haemoglobin, CRP and hepcidin. Oral iron did not alter disease activity; it improved Short IBDQ and Perceived Stress Questionnaire scores in adults. CONCLUSION: Oral ferrous sulphate was no less effective or well-tolerated in adolescents than adults, and did not increase disease activity in this short-term study. The inverse relation between baseline CRP and hepcidin levels and the haemoglobin response suggests that CRP or hepcidin measurements could influence decisions on whether iron should be given orally or intravenously. [ClinTrials.gov registration number NCT01991314].
Subject(s)
Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/drug therapy , Ferrous Compounds/therapeutic use , Hemoglobins/metabolism , Inflammatory Bowel Diseases/drug therapy , Administration, Oral , Adolescent , Adult , Anemia, Iron-Deficiency/etiology , Anemia, Iron-Deficiency/psychology , Feces/chemistry , Female , Ferritins/blood , Ferrous Compounds/administration & dosage , Ferrous Compounds/adverse effects , Hepcidins/blood , Humans , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/psychology , Intention to Treat Analysis , Leukocyte L1 Antigen Complex/analysis , Male , Prospective Studies , Quality of Life , Severity of Illness Index , Surveys and Questionnaires , Transferrin/metabolismABSTRACT
BACKGROUND: Inflammatory bowel disease unclassified (IBDU) is the rarest IBD subtype with treatment based on extrapolation from ulcerative colitis (UC) and Crohn's disease (CD) studies. We compared IBDU treatment choices with other colonic IBDs and explored long-term outcomes. METHODS: This was a multicenter retrospective longitudinal study of 23 centers of pediatric IBD with isolated colitis, including a mild ileitis consistent with backwash. RESULTS: Of note, 797 children (median age: 11.6 years, range: 2-18.4) were included: 250 with CD, 287 with UC, and 260 with IBDU (median follow-up: 2.8 [interquartile range: 1.6-4.2] years). IBDU differed from UC with lower corticosteroid (154 [59%] versus 204 [71%]; P = 0.004) and higher exclusive enteral nutrition use (26 [10%] versus 2 [0.6%]; P < 0.0001). Compared to patients with CD, patients with IBDU received less exclusive enteral nutrition and immunomodulators (26 [10%] versus 93 [37%]; P < 0.0001 and 67 [26%] versus 129 [52%]; P < 0.0001, respectively) but more aminosalicylates (228 [88%] versus 159 [64%]; P < 0.0001). Biological treatment was significantly higher in CD (82 [34%]) than in IBDU and UC (24 [12%] and 47 [17%], respectively; P < 0.0001). At last follow-up, 135 (69%) patients with IBDU had remission/mild disease activity compared with 100 (46%; P < 0.0001) patients with CD and 174 (64%; P = 0.3) patients with UC. Four (2%) of 194 patients with IBDU underwent surgery compared with 22 (8%) of 270 patients with UC (P = 0.009) and 20 (8%) of 238 patients with CD (P = 0.008). CONCLUSIONS: Children with IBDU have a lower medication burden and lower surgery rates than other IBD subtypes. The disease course at follow-up is generally mild, supporting an initial trial with 5-ASA before using more aggressive therapies.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Biological Products/therapeutic use , Enteral Nutrition , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/therapy , Adolescent , Child , Child, Preschool , Colitis, Ulcerative/therapy , Crohn Disease/therapy , Cyclosporine/therapeutic use , Female , Humans , Inflammatory Bowel Diseases/surgery , Longitudinal Studies , Male , Mesalamine/therapeutic use , Retrospective StudiesABSTRACT
BACKGROUND: Dendritic cells (DC) determine initiation, type and location of immune responses and, in adults, show decreased Toll-like receptors and some increased cytokine levels on ageing. Few studies in children have characterised DC or explored DC-related mechanisms producing age-related immune changes. RESULTS: The pDC marker BDCA2 (but not CD123) was absent in pre-pubertal children and numbers of pDC decreased with age. Blood and colonic DC were more mature and activated in adults. Decrease in pDC numbers correlated with reduced GM-CSF levels with aging, but increasing IL-4 and IL-8 levels correlated with a more activated DC profile in blood. CXCL16 levels decreased with age. METHODS: Blood and colonic DC phenotypes were determined in healthy adults and children by flow cytometry and correlated with aging. Blood DC were divided into plasmacytoid (pDC) and myeloid (mDC) while only mDC were identified in colon. Serum cytokine levels were determined by multiplex cytokine assays and correlated with DC properties. CONCLUSIONS: In children, lack of BDCA2, a receptor mediating antigen capture and inhibiting interferon induction, may be immunologically beneficial during immune development. Conversely, reduced pDC numbers, probably secondary to decreasing GM-CSF and increasing cytokine-induced maturation of DC are likely to determine deteriorating immunity with ageing.
Subject(s)
Biomarkers/metabolism , Colon/metabolism , Cytokines/metabolism , Dendritic Cells/metabolism , Myeloid Cells/metabolism , Adult , Age Factors , Cell Differentiation , Cells, Cultured , Child , Colon/cytology , Dendritic Cells/cytology , Humans , Myeloid Cells/cytologyABSTRACT
Ulcerative colitis (UC) in children is increasing. The range of treatments available has also increased too but around 1 in 4 children still require surgery to control their disease. An up-to-date understanding of treatments is essential for all clinicians involved in the care of UC patients to ensure appropriate and timely treatment while minimising the risk of complications and side effects.
Subject(s)
Colitis, Ulcerative/therapy , Child , Colitis, Ulcerative/diagnosis , Disease Management , Humans , Severity of Illness IndexABSTRACT
BACKGROUND: It has been speculated that pediatric Crohn's disease (CD) is a distinct disease entity, with probably different disease subtypes. We therefore aimed to accurately phenotype newly diagnosed pediatric CD by using the pediatric modification of the Montreal classification, the Paris classification. METHODS: Information was collected from the EUROKIDS registry, a prospective, web-based registry of new-onset pediatric IBD patients in 17 European countries and Israel. When a complete diagnostic workup was performed (ileocolonoscopy, upper gastrointestinal [GI] endoscopy, small bowel imaging), CD patients were evaluated for ileocolonic disease extent, esophagogastroduodenal involvement, and jejunal/proximal ileal involvement. Disease behavior and the occurrence of granulomas were also analyzed. RESULTS: In all, 582 pediatric CD patients could be classified according to the Paris classification. Isolated terminal ileal disease (± limited cecal disease) was seen at presentation in 16%, isolated colonic disease in 27%, ileocolonic disease in 53%, and isolated upper GI disease in 4% of patients. In total, 30% had esophagogastroduodenal involvement and 24% jejunal/proximal ileal disease. Patients with L2 disease were less likely to have esophagogastroduodenal involvement or stricturing disease than patients with L1 or L3 disease. Terminal ileal disease and stricturing disease behavior were more common in children diagnosed after 10 years of age than in younger patients. Granulomas were identified in 43% of patients. CONCLUSIONS: Accurate phenotyping is essential in pediatric CD, as this affects the management of individual patients. Disease phenotypes differ according to age at disease onset. The Paris classification is a useful tool to capture the variety of phenotypic characteristics of pediatric CD.
Subject(s)
Cecum/pathology , Colon/pathology , Crohn Disease/diagnosis , Ileum/pathology , Phenotype , Upper Gastrointestinal Tract/pathology , Adolescent , Age of Onset , Child , Child, Preschool , Crohn Disease/classification , Crohn Disease/complications , Endoscopy, Gastrointestinal , Europe , Female , Granuloma/etiology , Humans , Infant , Infant, Newborn , Israel , Logistic Models , Magnetic Resonance Imaging , Male , Prospective Studies , Registries , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: We have previously reported evidence of in vitro sensitisation to cow's milk protein in peripheral blood mononuclear cells (PBMCs) in preterm infants with necrotising enterocolitis (NEC). In the present study, we document the changes in the PBMC responses to stimulation with mitogen (phytohaemagglutinin) and cow's milk proteins ß-lactoglobulin (ß-lg) and casein over time: from the acute presentation of NEC, to initial recovery (reinitiation of enteral feeds), to full recovery (full feeding). METHODS: Of the 14 preterm infants recruited with acute NEC, 12 were followed until fully enterally fed (2 died during the acute phase). Cytokine secretion (interferon-γ [IFN-γ], interleukin 4, [IL-4], IL-10, and transforming growth factor-ß1 [TGF-ß1]) by PBMCs in response to stimulation by phytohaemagglutinin, ß-lg, and casein was measured by enzyme-linked immunospot in the acute phase and subsequently at recovery and full recovery. RESULTS: The high levels of cytokine secretion (IFN-γ, IL-4, IL-10, and TGF-ß1) observed in response to ß-lg and casein in the acute phase increased by a further 50% to 100% at recovery (P < 0.005). At full recovery (full feeding), however, IFN-γ, IL-4, and IL-10 secretion response had returned to, or below, acute-phase levels, whereas the augmented TGF-ß1 response was maintained (P = 0.005 vs acute level). This response pattern was similar for casein, and did not appear to be influenced by the nature of the feed used following NEC (breast milk/formula/hydrolysed formula). CONCLUSIONS: The evolution of the cytokine response profile in parallel with the clinical recovery from NEC is consistent with a putative role for TGF-ß1 in regulation of inflammation, and possibly also oral tolerance.
Subject(s)
Cytokines/metabolism , Enterocolitis, Necrotizing/immunology , Infant, Newborn, Diseases/immunology , Infant, Premature/immunology , Inflammation/immunology , Milk Hypersensitivity/immunology , Milk Proteins/immunology , Animals , Caseins/immunology , Caseins/pharmacology , Cattle , Enterocolitis, Necrotizing/metabolism , Enterocolitis, Necrotizing/therapy , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/metabolism , Infant, Newborn, Diseases/therapy , Infant, Premature/metabolism , Inflammation/metabolism , Inflammation Mediators/blood , Lactoglobulins/immunology , Lactoglobulins/pharmacology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Longitudinal Studies , Male , Milk , Milk Hypersensitivity/metabolism , Milk Proteins/pharmacology , Nutritional Support , Phytohemagglutinins/immunology , Phytohemagglutinins/pharmacology , Transforming Growth Factor beta1/metabolismABSTRACT
Combined immunosuppression by immunomodulators and biological therapy has become standard in the medical management of moderate-to-severe inflammatory bowel disease (IBD) because of clearly demonstrated efficacy. Clinical studies, registries, and case reports warn of the increased risk of infections, particularly opportunistic infections; however, already in the steroid monotherapy era, patients are at risk because it is accepted that a patient should be considered immunosuppressed when receiving a daily dose of 20 mg of prednisone for 2 weeks. Prescriptions increasingly involve azathioprine, methotrexate, and various biological agents. The TREAT registry evaluated safety in >6000 adult patients, half of them treated with infliximab (IFX) for about 1.9 years. IFX-treated patients had an increased risk of infections and this was associated with disease severity and concomitant prednisone use. The REACH study, evaluating the efficacy of IFX in children with moderate-to-severe Crohn disease, refractory to immunomodulatory treatment, reports serious infections as the major adverse events and their frequency is higher with shorter treatment intervals. The combination of immunosuppressive medications is a risk factor for opportunistic infections. Exhaustive guidelines on prophylaxis, diagnosis, and management of opportunistic infections in adult patients with IBD have been published by a European Crohn's and Colitis Organization working group, including clear evidence-based statements. We have reviewed the literature on infections in pediatric IBD as well as the European Crohn's and Colitis Organization guidelines to present a commentary on infection prophylaxis for the pediatric age group.
Subject(s)
Antibodies, Monoclonal/adverse effects , Immunosuppressive Agents/adverse effects , Inflammatory Bowel Diseases/complications , Opportunistic Infections/etiology , Prednisone/adverse effects , Drug Therapy, Combination/adverse effects , Europe , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab , Opportunistic Infections/prevention & control , Risk Factors , Severity of Illness Index , Societies, MedicalABSTRACT
BACKGROUND: Crohn's disease and ulcerative colitis are complex disorders with some shared and many unique predisposing genes. Accurate phenotype classification is essential in determining the utility of genotype-phenotype correlation. The Montreal Classification of IBD has several weaknesses with respect to classification of children. The dynamic features of pediatric disease phenotype (change in disease location and behavior over time, growth failure) are not sufficiently captured by the current Montreal Classification. METHODS: Focusing on facilitating research in pediatric inflammatory bowel disease (IBD), and creating uniform standards for defining IBD phenotypes, an international group of pediatric IBD experts met in Paris, France to develop evidence-based consensus recommendations for a pediatric modification of the Montreal criteria. RESULTS: Important modifications developed include classifying age at diagnosis as A1a (0 to <10 years), A1b (10 to <17 years), A2 (17 to 40 years), and A3 (>40 years), distinguishing disease above the distal ileum as L4a (proximal to ligament of Treitz) and L4b (ligament of Treitz to above distal ileum), allowing both stenosing and penetrating disease to be classified in the same patient (B2B3), denoting the presence of growth failure in the patient at any time as G(1) versus G(0) (never growth failure), adding E4 to denote extent of ulcerative colitis that is proximal to the hepatic flexure, and denoting ever severe ulcerative colitis during disease course by S1. CONCLUSIONS: These modifications are termed the Paris Classification. By adhering to the Montreal framework, we have not jeopardized or altered the ability to use this classification for adult onset disease or by adult gastroenterologists.
Subject(s)
Inflammatory Bowel Diseases/classification , Adolescent , Adult , Age Factors , Age of Onset , Child , Child, Preschool , Colitis, Ulcerative/classification , Colitis, Ulcerative/pathology , Crohn Disease/classification , Crohn Disease/pathology , Disease Progression , Humans , Infant , Inflammatory Bowel Diseases/pathology , Severity of Illness Index , Young AdultABSTRACT
AIMS: To assess self-reported QoL in children with achalasia aged 5-18 and compare this with both disease and healthy control children in a prospective study. METHODS: All children diagnosed with achalasia at one hospital were asked to participate in this study by completing the self-report module of the validated PedsQL™ generic QoL assessment. All children attending a tertiary paediatric gastroenterology clinic from February 2009 to May 2009 with chronic constipation or inflammatory bowel disease were asked to participate in this study as disease controls. The PedsQL™ considers physical, emotional, social and school domains and is scored from 0-100. Healthy children were also recruited from the same site. Groups were compared using Analysis of Variance with Tukey's post-hoc test. RESULTS: One hundred and sixty one children completed the assessment (90 (56%) male, mean age 11.3 yrs ± 3.4 years) including 17 children with achalasia, 44 with chronic constipation, 59 with inflammatory bowel disease and 41 healthy children. QoL was significantly lower in the achalasia group compared to both children with IBD (73 vs. 82, p = 0.035) and healthy children (73 vs. 84, p = 0.005), and was comparable to that of children with chronic constipation (73 vs. 74, p = 0.99). CONCLUSION: Children with achalasia report a significantly lower QoL compared to children with inflammatory bowel disease and healthy children.
Subject(s)
Esophageal Achalasia/physiopathology , Esophageal Achalasia/psychology , Adolescent , Case-Control Studies , Child , Constipation/physiopathology , Constipation/psychology , Female , Humans , Inflammatory Bowel Diseases/physiopathology , Inflammatory Bowel Diseases/psychology , London , Male , Prospective Studies , Quality of Life , Sickness Impact ProfileABSTRACT
OBJECTIVE: The aim of this study was to evaluate the results of surgery in children with Crohn disease (CD) not responding to medical therapy and establish whether surgery improves growth and nutrition. PATIENTS AND METHODS: Children with CD diagnosed between 1998 and 2008 were reviewed. Relapse was defined by Harvey-Bradshaw index >5. Data, reported as median (range), were compared by Fisher exact test and repeated-measures ANOVA. RESULTS: One hundred forty-one children, ages 12.7 years (3.5-16.8), were identified; 27 (19%) required surgery 14.5 months (1.1-61.8) after diagnosis. Twenty-one had elective surgery (19 isolated ileocaecal disease and stricture, 2 diffuse disease of ileum); 6 had emergency surgery (3 peritonitis, 2 haemorrhage, 1 perforation). Surgery included 18 ileocaecal resection and end-to-end anastomosis, 5 stoma formation, 2 left hemicolectomy and end-to-end anastomosis, and 2 stricturoplasty. Follow-up was 2.5 years (1-9.4). Growth and nutrition improved by 6 and 12 months after surgery, with a significant increase in weight z score (P < 0.0001), height z score (P < 0.0001), albumin (30 [13-36] vs 39 [30-46] vs 40 [33-45], P < 0.0001), and haemoglobin [10 (6.8-13.2) vs 11.7 (8.2-13.7) vs 12.0 (9.3-14.7), P < 0.0001]. All patients of the received azathioprine (2-2.5 mg · kg⻹ · day⻹) after surgery. Fifteen patients (55%) relapsed with a modified Harvey-Bradshaw index of 8 (6-11) within 11.5 months (4.2-33.4). Of these, 5 patients (18%) relapsed within 1 year. Five patients (18%) had further surgery (2 anastomotic strictures, 2 diseased stoma, and 1 enterocutaneous fistula). CONCLUSIONS: Growth and nutrition following surgery for CD improve, but there is a high relapse rate. Despite this, the improved growth and nutrition before relapse may be beneficial during puberty and justify surgery in children not responding to medications.