OBJECTIVES:The aim of this study was to evaluate the effectiveness and safety of adalimumab (ADA) in children with ulcerative colitis (UC) previously treated with infliximab (IFX).
...METHODS:Retrospective study including children with UC from a national registry who received ADA therapy. The primary endpoint was the rate of corticosteroid-free remission at week 52. Secondary outcomes were the rate of sustained clinical remission, primary nonresponse, and loss of response at weeks 12, 30, and 52 and rate of mucosal healing and side effects at week 52.
RESULTS:Thirty-two children received ADA (median age 10 ± 4 years). Median disease duration before ADA therapy was 27 months. All patients received previous IFX (43% intolerant, 50% nonresponders 37.5% primary, 42.5% secondary nonresponders, 6.7% positive anti-IFX antibodies). Fifty-two weeks after ADA initiation, 13 patients (41%) were in corticosteroid-free remission. Mucosal healing occurred in 9 patients (28%) at 52 weeks. The cumulative probability of a clinical relapse-free course was 69%, 59%, and 53% at 12, 30, and 52 weeks, respectively. Ten patients (31%) had a primary failure and 5 (15%) a loss of response to ADA. No significant differences in efficacy were reported between not-responders and intolerant to IFX (P = 1.0). Overall, 19 patient (59%) maintained ADA during 52-week follow-up. Seven patients (22%) experienced an adverse event, no serious side effects were observed and none resulted in ADA discontinuation.
CONCLUSIONS:Based on our data, ADA seems to be effective in children with UC, allowing to recover a significant percentage of patients intolerant or not-responding to IFX. The safety profile was good.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and Aims:
Recent epidemiological studies showed an increase in ulcerative colitis among children, especially in its aggressive form, requiring surgical treatment. Although medical ...therapeutic strategies are standardized, there is still no consensus regarding indications, timing and kind of surgery. This study aimed to define the surgical management of paediatric ulcerative colitis and describe attitudes to it among paediatric surgeons.
Methods:
This was a retrospective cohort study. All national gastroenterology units were invited to participate. From January 2009 to December 2013, data on paediatric patients diagnosed with ulcerative colitis that required surgery were collected.
Results:
Seven units participated in the study. Seventy-one colectomies were performed (77.3% laparoscopically). Main surgical indications were a severe ulcerative colitis attack (33.8%) and no response to medical therapies (56.3%). A three-stage strategy was chosen in 71% of cases. Straight anastomosis was performed in 14% and J-pouch anastomosis in 86% of cases. A reconstructive laparoscopic approach was used in 58% of patients. Ileo-anal anastomosis was performed by the Knight–Griffen technique in 85.4% and by the pull-through technique in 9.1% of patients. Complications after colectomy, after reconstruction and after stoma closure were reported in 12.7, 19.3 and 35% of cases, respectively.
Conclusions:
This study shows that there is general consensus regarding indications for surgery. The ideal surgical technique remains under debate. Laparoscopy is a procedure widely adopted for colectomy but its use in reconstructive surgery remains limited. Longer follow-up must be planned to define the quality of life of these patients.
Abstract
Background
This study aimed to define clusters of disease activity and prognostic factors of disease course in a well-characterized cohort of children with Crohn’s disease (CD).
Methods
All ...patients from the SIGENP IBD (Italian Society of Pediatric Gastroenterology Hepatology and Nutrition Inflammatory Bowel Disease) registry with a 5-year follow-up and 6-monthly evaluation were included. Active disease was defined for each semester as follows: clinical activity (weighted Pediatric Crohn’s Disease Activity Index ≥12.5 or Mucosal Inflammation Noninvasive Index ≥8) and active disease on endoscopy (Simple Endoscopic Score for Crohn’s Disease >3 or fecal calprotectin >250 µg/g) or imaging. Formula-based clusters were generated based on previously published patterns in adults.
Results
Data from 332 patients were analyzed. A total of 105 (32%) experienced a quiescent disease course; 49 (15%) and 31 (9%) a moderate-to-severe chronically active and chronic intermittent disease, respectively; 104 (31%) and 43 (13%) had active disease in the first 2 years after diagnosis and remission thereafter and vice versa, respectively. Surgery at diagnosis was significantly associated with a quiescent course (odds ratio OR, 10.05; 95% confidence interval CI, 3.05-25.22; P=.0005), while growth impairment at the diagnosis and active disease requiring corticosteroids at 6 months were inversely related to the quiescent group (OR, 0.48; 95% CI, 0.27-0.81; P= .007; and OR, 0.35; 95% CI, 0.16-0.71; P= .005, respectively). Perianal involvement at diagnosis and moderate–severe activity at 6 months correlated with disease progression (OR, 3.85; 95% CI, 1.20-12.85; P=.02).
Conclusions
During the first 5 years of follow-up, one-third of children with CD experience a quiescent course. However, another one-third have a moderate-to-severe disease course. Surgery at the diagnosis is related to a quiescent course, while growth impairment and lack of response to induction therapy correlate with more severe disease activity during follow-up.
Abstract
Background
Anemia is a common extraintestinal manifestation in inflammatory bowel disease (IBD) with an impact on patients’ quality of life. Our aim was to determine the prevalence of anemia ...and its characteristics at the diagnosis in children with inflammatory bowel disease (IBD) and to investigate its trend during follow-up.
Methods
We conducted an observational, multicenter cohort study including data of IBD children with anemia at the diagnosis enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) IBD registry. Demographic, clinical, laboratory and endoscopic data were collected at the diagnosis and anemia trend was evaluated at 1-year follow-up. Anemia was diagnosed based on the WHO criteria and classified as mild, moderate, and severe accordingly.
Results
Five hundred eighty-nine 295 CD (50%) and 294 UC/IBDU (50%) out of 1634 with IBD presented with anemia, resulting in a prevalence of 36%. Anemia rate was higher in CD than in UC (39% vs 33%, p = 0.009). Most patients presented at the diagnosis with moderate anemia (55%). The most common forms of anemia were iron deficiency anemia (IDA) and combined inflammatory and IDA anemia (InflIDA), both present in 42% of children. Only 15% of children had anemia of inflammation. Children with CD had higher rates of mild anemia than UC (38% vs 33%, p<0.0001), while severe anemia was more common in UC (13% vs 6%, p= 0.001) as well as IDA (53% vs 31%, p<0.0001). Younger age and lower albumin levels significantly correlated with the severity of the anemia in CD. In UC, females were more likely to experience severe anemia (69% vs 47%, p=0.02) and an extensive disease was more prevalent in children with moderate and severe anemia then in those with mild anemia (p=0.01 and p=0.03, respectively). At 1 year, 99 children (17%) were still anemic. At multivariable logistic regression analysis, baseline wPCDAI and SES-CD significantly correlated with the persistence of anemia at 1 year in CD. No variables correlated with the persistence of anemia in UC.
Conclusion
More than one-third of pediatric patients present with anemia at the diagnosis of IBD, most commonly moderate. A severe anemia is most common in UC compared to CD. Iron deficiency anemia (alone or in its form of InflIDA) is the most common cause of anemia in children with IBD. One out of five is still anemic after 1 year from the diagnosis.
Anal canal duplication (ACD) represents an extremely rare intestinal congenital anomaly of unknown origin. Usually evidenced within 2 years of age, nearly 45% of reported cases present associated ...malformations such as presacral mass, anorectal malformation (ARM) and genitourinary anomalies. The confirmative diagnosis is histopathological, with evidence of an anal mucosal lining (squamous +/- transitional epithelium), surrounded from a smooth muscle coat and anal glands. We review a conjoined experience from two European pediatric surgical departments. From 1970 to 2005, 12 patients were observed, seven in Pescara, Italy (1997-2005), five in Barcelona, Spain (1970-2004) - mean age at diagnosis 17.8 months, range 0-60; M:F = 1:11. Clinical presentation, diagnostic-surgical approach, and complications were reviewed. According to clinical presentation, patients could be divided in three age groups: asymptomatic (mean age 4.8 months, six patients - one with an associated complex genitourinary malformation, one with a presacral mature teratoma, one with ACD evidenced hysthologically on a retroanal mass removed during the correction of an ARM), mildly symptomatic - constipation, mucous discharge (mean age 29.2 months, four patients - one with associated presacral ependymoma and intestinal neuronal dysplasia type B, one with presacral mass) and complicated - perineal abscess, recurrent fistula (mean age 34 months, two patients). In 11 cases a perianal orifice was evident (ten posteriorly located). The pelvic-MRI was the preferred diagnostic tool in Pescara (5/7, with presacral mass in two patients), fistulography in Barcelona (5/5), where one presacral mass was discovered intraoperatively. Eleven patients underwent surgical removal of the ACD (five perineal approach, five posterior sagittal approach, and one PSARP). Histopathological findings confirmed the diagnosis in operated cases (11). The parents of the male patient denied the consent to surgical treatment. The only major post-operative complication was a sphincteric insufficiency (one case), surgically treated. When facing a perianal orifice, attention should be paid to ACD, particularly in female patients with coexistent genitourinary or intestinal malformations. Pelvic US and MRI are the gold standard to evidence the not rarely associated presacral mass. Surgical early removal (mucosectomy or perineal/posterior sagittal approach, depending on length of ACD and associated presacral mass) is warranted, also in asymptomatic patients, because of the risk of inflammatory complications and cancer (the latter reported in literature in adults).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background
This study aimed to define clusters of disease activity and prognostic factors of the disease course in a well-characterized cohort of children with Crohn’s disease (CD).
Methods
...All patients with CD identified from the SIGENP IBD registry with a follow-up of at least 5 years and a 6-monthly evaluation were included. Active disease was defined for each yearly semester as follows: clinical activity (wPCDAI≥12,5 or MINI index ≥8), need for treatment escalation, hospitalization, or surgery, active disease on endoscopy (SES-CD >3) or imaging. Formula-based clusters were generated based on previously published patterns in adults 1. Prediction models were created based on clinical, surgical, endoscopic, and laboratory findings at diagnosis and at 6-month follow-up.
Results
Data from 332 patients were analyzed. Ninety-six (29%) had a quiescent course; 52 (16%) and 34 (10%) had a moderate-to-severe chronically active and chronic intermittent disease; 107 (32%) and 43 (13%) had an active disease in the first two years after diagnosis and remission thereafter and the opposite course, respectively. Overall, 129 (39%) children presented with an active disease at 5 years of follow-up, with no patient off-therapy. Surgery at the time of diagnosis was significantly associated with a quiescent course OR 10.05 (CI 3,05-25,22), p 0.0005, while growth impairment at the diagnosis and moderate-severe activity requiring corticosteroids at 6 months were inversely related to the quiescent group OR 0.48 (CI 0,27-0,81) p 0.007 and OR 0.35 (CI 0,16-0,71) p 0.005, respectively. Perianal involvement at diagnosis and moderate-severe activity at 6 months positively correlated with disease progression (i.e., B1 to B2/B3) at follow-up OR 2.55 (CI 1,05-6,07) p<0.04 and OR 3.85 (CI 1,20-12,85) p 0.02. Seventy-three patients (22%) required surgery, of which 31 (43%) in the first 6 months after diagnosis.
Conclusion
Approximately one-third of our cohort of children with CD had a quiescent course during the first five years after diagnosis. In contrast, more than one-third of the patients had a chronically or intermittently active disease during the entire follow-up, or an initial remission followed by a persistent activity. Surgery at the time of diagnosis, mild disease onset without growth impairment, and lower disease activity without corticosteroid use in the first six months after diagnosis predicted a quiescent course over time.
1. Wintjens D., Bergey F., Saccenti E. et al. Disease activity patterns of Crohn's disease in the first ten years after diagnosis in the population-based IBD South Limbrug Cohort. J Crohns Colitis. 2021; 15 (3):391-400.
Abstract
Background
The aim of mucosal healing (MH) as a therapeutic target in paediatric inflammatory bowel diseases (IBD) has emphasised the role of the endoscopy. There is a great variability in ...evaluating mucosal lesions among different operators, especially in paediatric patients. This multicentre prospective study aims to evaluate the interobserver agreement among paediatric endoscopists in using validated endoscopic scores of IBD in children.
Methods
Fifteen videos of follow-up ileocolonoscopies in children with IBD (8 ulcerative colitis –UC-, 7 Crohn’s disease –CD-) were selected from 3 different referral sites in Italy. Eleven paediatric endoscopists from different centres were asked to evaluate all videos as independent and blinded readers. The scoring systems used were ulcerative colitis Endoscopic Index of Severity (UCEIS) for UC and simple endoscopic score for Crohn’s disease (SES-CD) for CD. Kappa statistics and intraclass correlation coefficients were used to measure agreement. Furthermore, an experienced adult gastroenterologist evaluated the same videos and scores them. His results were compared with paediatric endoscopists’ findings.
Results
The median age of the participants was 40 (interquartile range: 6) with a median experience of 12 (14) years in centres with a median number of 140 (230) of paediatric IBDs. Intercluster correlation agreement was 0.298 (95% CI: 0.13–0.55) for UC and 0.266 (0.11–0.52) for CD. When a disease activity categorisation was adopted (remission, moderate, mild and severe) Fleiss’ kappa coefficient was 0.408 (0.29–0.53) for UC and 0.552 (0.43–0.73) for CD (Figure 1). When stratified for item vascular pattern of UC was the most reliable item IC: 0.624 (0.321–0.854). The comparison between paediatric and expert gastroenterologist’s scores is shown in Figure 2. In the multivariate analysis none of the reviewer characteristic affected the readers’ errors.
Conclusion
This pilot multicentre study shows that there is a low level of agreement among paediatric endoscopists in evaluating children with IBDs. Agreement improved after using a disease activity categorisation, with better results for CD. Regardless to experience, all readers showed a low-grade accordance with adult gastroenterologist. According to these findings, the use of scoring systems should be implemented for all paediatric endoscopists. Future specific training programs should be considered to pursue this goal.
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