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Acute severe ulcerative colitis in children: a systematic review
1Pediatric Gastroenterology Unit, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel. turnerd@szmc.org.il
Insights
Pediatric ulcerative colitis (UC) is severe, with a 34% steroid-failure rate. Early use of the Pediatric UC Activity Index (PUCAI) guides treatment, with biologics like infliximab offering effective alternatives to cyclosporine.
Area of Science:
- Pediatric Gastroenterology
- Inflammatory Bowel Disease Research
- Clinical Trial Analysis
Background:
- Pediatric ulcerative colitis (UC) presents with a more severe phenotype, characterized by extensive disease and frequent acute severe exacerbations.
- A significant pooled steroid-failure rate of 34% (95% CI: 27%-41%) highlights the need for effective management strategies in children.
Purpose of the Study:
- To review and synthesize current evidence on managing severe pediatric ulcerative colitis.
- To provide guidance on corticosteroid dosing, the role of nutritional support, interpretation of imaging, and the utility of activity indices.
- To evaluate the efficacy of second-line therapies including cyclosporine and infliximab, and to discuss surgical considerations.
Main Methods:
- Systematic review and meta-analysis of pooled data from multiple studies on pediatric UC.
- Analysis of steroid-failure rates, efficacy of immunosuppressants and biologics, and outcomes of colectomy.
- Utilized the Pediatric UC Activity Index (PUCAI) for predicting treatment response and guiding therapy escalation.
Main Results:
- Pooled steroid-failure rate in 291 children was 34%. Recommended corticosteroid dosing: 1-1.5 mg/kg daily (up to 40-60 mg).
- The Pediatric UC Activity Index (PUCAI) at day 3 (>45 points) predicts steroid failure, and at day 5 (>65-70 points) indicates need for second-line therapy.
- Cyclosporine (81% short-term success) and infliximab (75% short-term response, 64% 1-year response) are effective, with cyclosporine use limited to 3-4 months bridging to thiopurines.
Conclusions:
- Early assessment using PUCAI is crucial for timely escalation of therapy in pediatric UC.
- Biologic therapies like infliximab offer comparable efficacy to cyclosporine, providing valuable options for refractory cases.
- Colectomy is a consideration for toxic megacolon, medically refractory disease, or chronic severe cases, requiring careful evaluation of long-term outcomes and quality of life.
Abstract:
Pediatric ulcerative colitis (UC) has a more severe phenotype, reflected by more extensive disease and a higher rate of acute severe exacerbations. The pooled steroid-failure rate among 291 children from five studies is 34% (95% confidence interval [CI]: 27%-41%). It is suggested that corticosteroids should be dosed between 1-1.5 mg/kg up to 40-60 mg daily. Food restriction has a limited role in severe UC and should be generally discouraged in children who do not have a surgical abdomen. Appraisal of radiologic findings in children must recognize the variation in colonic width with age and size. Data suggest that the Pediatric UC Activity Index (PUCAI), determined at day 3, should be used to screen for patients likely to fail corticosteroids (>45 points), and at day 5 to dictate the introduction of second-line therapy (>65-70 points). Cyclosporine is successful in children with severe colitis but its use should be restricted to 3-4 months while bridging to thiopurine treatment (pooled short-term success rate 81% [95% CI: 76%-86%]; n = 94 from eight studies). Infliximab may be as effective as cyclosporine (75% pooled short-term response (95% CI: 67%-83%); n = 126, six studies) with a pooled 1-year response of 64% (95% CI: 56%-72%). In toxic megacolon, in patients refractory to one salvage medical therapy, and in chronic severe disease, colectomy may be preferred. Decision-making regarding colectomy in children must consider the toxicity of medication consumed over many future years, the quality of life and self-image associated with either choice, as well as both functional outcomes and, in females, fertility following pouch procedures.
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