Management of acute severe ulcerative colitis in children

The incidence of pediatric-onset ulcerative colitis (UC) is rising. Children often present with a more severe disease phenotype as compared to adults with over a third requiring hospitalization for the management of acute severe ulcerative colitis (ASUC). Further, in pediatric patients presenting with inflammatory bowel disease (IBD) limited to the colon, a definitive diagnosis of UC vs. Crohn’s disease is often unclear. Here, we review the unique aspects of pediatric ASUC including the epidemiology, diagnosis, medical, and surgical management of this disease.     

Surgery for ulcerative colitis in pediatric patients: functional results of 10-year follow-up with straight endorectal pull-through

Children and adolescents affected by ulcerative colitis (UC) frequently require colectomy because of refractory or chronic symptoms. The aim of this paper is to present our experience and 10-year follow-up results of 28 patients who underwent endorectal pull-through (ERPT) as surgical treatment for UC, with special regard to surgical complications, stooling patterns (frequency of defecation, stool consistency, urgency period), fecal incontinence, and quality of life. A retrospective chart review of these patients was performed to evaluate age at colectomy, indication for surgical treatment, operative procedures, technical details, and early or late complications. Frequency of defecation was less than twice per day in two patients, between three and five times per day in nine patients, and more than six times per day in 10 patients. Stool consistency was normal in 14 patients, loose in five, and liquid in only two cases. Urgency period was normal (minutes) in 14 patients, short (seconds) in four, and absent in three. Ten patients (47%) have perfect or good fecal continence, whereas 11 (52%) patients present moderate to total incontinence. The self-reported emotional health was good in most of the patients. A large number are progressing well at school and are coping with their operations. Studies of quality of life in UC patients who underwent surgical treatment in childhood or adolescence, comparing as well the results according to the surgical technique adopted, must be encouraged.     

Infliximab as a novel therapy for pediatric ulcerative colitis

OBJECTIVES: The role of infliximab (anti-tumor necrosis factor alpha antibody) therapy in ulcerative colitis (UC) is not well defined. There are only two reports published describing its use in UC. The authors describe their experience with open-label use of infliximab in children with moderate to severe UC. METHODS: The authors collected data on all consecutive pediatric patients with UC who received infliximab at The Children's Hospital of Philadelphia until July 2001. The primary measured outcome was clinical response at 2 days and 2 weeks after infliximab infusion, as measured by the Lichtiger colitis activity index (LCAI) score and the Physician Global Assessment (PGA). Tolerance of the infusions and adverse events were recorded. RESULTS: Nine patients qualified for clinical response analysis. The median Lichtiger colitis activity index score decreased from 11 before the infusion to 1 at 2 days and 2 weeks after the infusion, respectively (P = 0.01 for 2 days and 2 weeks). Seven of nine (77%) patients had decreased activity of their disease measured by the Physician Global Assessment. Corticosteroid therapy was discontinued in six (66%) patients. An infusion reaction developed (generalized pruritus and facial flushing) in two patients and an elevated anti-nuclear antibody (ANA) titer of 1:1280 developed in one patient. CONCLUSION: Infliximab is associated with short-term clinical improvement in children and adolescents with moderate to severe UC.     

Nieinwazyjna diagnostyka zmian zapalnych błony śluzowej jelita w nieswoistych zapaleniach jelit u dzieci

To achieve clinical remission was the primary target in medical therapy of both types of inflammatory bowel diseases (IBD): ulcerative colitis (UC) and Crohn's Disease (CD). Currently, however, it is mucosal healing to be the most important factor in beneficial change of natural history of IBD. Mucosal healing is associated with sustained clinical remission, reduced rate of hospitalization and surgical procedures. Therefore, assessment of the grade of intestinal inflammation is important to establish and to monitor a proper medical treatment.     

Dynamic pathology for circulating free DNA in a dextran sodium sulfate colitis mouse model

Purpose

In sepsis, circulating free DNA (cf-DNA) is increased, and is a marker of severity and prognosis of septic patients. This study aimed to evaluate cf-DNA in a dextran sodium sulfate-induced colitis mouse model, and its clinical implications.

Methods

Dynamic pathology of the cecum wall in the DSS-induced colitis mouse model was analyzed using multiphoton microscopy (MPM). Plasma cf-DNA concentrations in colitis mouse were quantified using PicoGreen dsDNA Assay Kit. Plasma cf-DNA was also measured in 123 human ulcerative colitis (UC) patients [mean age: 35.9 years (3–75 years) with 20 pediatric patients] to assess its relationships with clinical severity and Matt’s grade.

Results

Real-time images of cf-DNA were detected in the colitis model. The amount of labeled cf-DNA in the circulation of the colitis mice group was significantly higher compared with that in the control group (P < 0.05). In human UC blood samples, plasma cf-DNA concentrations in UC patients were significantly positively correlated with the clinical severity of UC and Matt’s grade (P < 0.05, P < 0.05, respectively).

Conclusions

Using MPM, we observed and analyzed real-time images of cf-DNA in a colitis mouse model. Plasma cf-DNA is a potential non-invasive blood marker for reflecting clinical severity and mucosal damage in UC patients.     

Ulcerative colitis associated with Takayasu's arteritis in a child

Takayasu's arteritis (TA) and ulcerative colitis (UC) are chronic inflammatory diseases of unknown aetiology, and their coexistence is very rare.
A 14-year-old Turkish girl presented with abdominal pain, nausea, vomiting and weight loss. UC was diagnosed based on physical examination and laboratory investigations and was confirmed by colonoscopic biopsies. TA developed approximately 1 year later, and was diagnosed with angiography performed for ongoing severe abdominal pain in spite of well-controlled UC.
Patients suffering from chronic inflammatory diseases such as UC must be investigated for other inflammatory diseases such as TA, especially if the response to immunosuppressant therapy is unsatisfactory.
Conclusion:  Findings from our patients suggest that paediatricians must remain alert to the possibility of abdominal vasculitis in patients with UC and unresolved abdominal pain in spite of clinical remission.     

儿童炎症性肠病53例临床分析

目的　探讨儿童炎症性肠病 (IBD)的临床特点 ,以提高儿童IBD的诊治和管理水平。方法　对 1992～2 0 0 2年 5 3例IBD患儿的临床资料进行回顾性分析。结果　IBD的患病率逐渐增加 ,5 3例IBD中克罗恩病 (CD)2 6例 ,溃疡性结肠炎 (UC) 2 7例。 2 7%的CD和 4 5 %的UC发病在 6岁以下 ,有 5例 (19% )UC发病在 1岁以内 ;男女性别无显著性差异 (P >0 0 5 ) ;发病至确诊平均时间CD为 5 0周 ,UC为 4 8周。临床表现CD以发热、腹痛为主要表现 ,UC以腹泻、便血为主要表现 ;胃肠外表现CD可见口腔溃疡、关节炎等 ,UC可见肛周病变、口腔溃疡等 ,两组患儿生长发育障碍的发生率均较高 (CD 6 5 % ,UC 5 9% ,P >0 0 5 )。病理改变CD以破坏和慢性增殖改变并存为特点 ,病灶均累及回肠末端及回盲部 ;而UC以急性炎症和渗出为主 ,病灶均累及直肠。外科合并症的发生率CD为 15 4 % ,UC为 14 8% ;儿童IBD治疗效果不满意 ,短期缓解率CD为 5 9% ,UC为 5 6 %。结论　IBD可以累及包括婴幼儿在内的各年龄组儿童 ,诊断的滞后以及缺乏系统的管理是临床亟待解决的问题。     

Secondary pouchitis in a pediatric patient successfully treated by salvage surgery

Apart from primary pouchitis, patients with secondary pouchitis caused by surgical complications require surgical management. The use of abdomino‐anal salvage surgery to treat secondary pouchitis caused by surgical complications in pediatric patients with ulcerative colitis (UC) has not been reported in detail. A girl was diagnosed with UC at 8 years old. She underwent restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) at 9 years old. She presented at 12 years old because of chronic antibiotic‐refractory pouchitis. The fistula and stricture failed to improve despite multiple local salvage surgeries and ileostomy construction. At 15 years old, she underwent redo IPAA. The patient was well at 20 years old with no signs of pouchitis. Early treatment by abdomino‐anal salvage surgery might be indicated to improve quality of life in pediatric patients with secondary pouchitis caused by surgical complication unresponsive to defunctioning and local salvage surgery.     

Clinical disease activity and inflammatory activity in the rectum in relation to mucosal inflammation assessed by colonoscopy. A study of children and adolescents with chronic inflammatory bowel disease

The relationship between clinical disease activity, rectal inflammatory activity and mucosal inflammation established at total colonoscopy has been studied in 36 young patients with ulcerative colitis (UC) and 24 with Crohn's colitis (CC). Semiformed stools, diarrhea and frequent bowel movements seem to be better indicators of extensive mucosal inflammation of a moderate or severe degree than blood in faeces. There were, however, several patients with a discrepancy between the degree of clinical disease activity and the extent and degree of mucosal inflammation at endoscopic and histologic assessment. In about one-third of the patients with UC and in about half of the patients with CC, who had mucosal inflammatory activity of a moderate or severe degree, the rectal inflammatory activity was of a lower degree. Total colonoscopy seems to be necessary in order to establish the extent and degree of mucosal inflammation.     

Clinical Disease Activity and Inflammatory Activity in the Rectum in Relation to Mucosal Inflammation Assessed by Colonoscopy A Study of Children and Adolescents with Chronic Inflammatory Bowel Disease

ABSTRACT. The relationship between clinical disease activity, rectal inflammatory activity and mucosal inflammation established at total colonoscopy has been studied in 36 young patients with ulcerative colitis (UC) and 24 with Crohn's colitis (CC). Semiformed stools, diarrhea and frequent bowel movements seem to be better indicators of extensive mucosal inflammation of a moderate or severe degree than blood in faeces. There were, however, several patients with a discrepancy between the degree of clinical disease activity and the extent and degree of mucosal inflammation at endoscopic and histologic assessment. In about one-third of the patients with UC and in about half of the patients with CC, who had mucosal inflammatory activity of a moderate or severe degree, the rectal inflammatory activity was of a lower degree. Total colonoscopy seems to be necessary in order to establish the extent and degree of mucosal inflammation.     

Inflammatory bowel disease in children: a pediatrician's perspective

Crohn's disease (CD) and ulcerative colitis (UC) are common and heterogeneous chronic inflammatory bowel disorders of childhood that account for up to 25% of all patients with inflammatory bowel disease (IBD). In CD, the familial pattern of disease concordance would suggest that genetics contribute to disease etiology. Children are more likely to have proximal small bowel disease complicated by stricture formation, fistulization and the need for surgical intervention. The predisposition for small bowel disease has been associated with mutations of the nucleotide oligomerization domain 2 (NOD2)/Caspase activation and recruitment domain 15 (CARD15) gene on chromosome 16 in 1/3 of patients with CD. Homozygous patients also show an early age at disease onset and a relatively high relative risk for isolated stricturing distal ileal disease. The potential clinical role for NOD2 testing in either the diagnosis or the therapeutic management of patients with CD has yet to be determined. The precise age of onset of CD and UC can be difficult in children. Subclinical phases of disease can be identified through a decrease in weight and height velocity, and a delay in pubertal development. However, a confident distinction between CD and UC also remains a taxonomic dilemma in 25% of pediatric patients with IBD, despite recent technological advances in diagnostic techniques, including gadolinium enhanced magnetic resonance imaging (MRI) and capsule endoscopy, and serological testing. The early introduction of immunomodulators, including azathioprine and 6-mercaptopurine have proven efficacy in maintaining long-term remission without concurrent corticosteroids. The pharmacogenomic of 6-MP metabolism has been shown to be useful in predicting susceptibility to antimetabolite induced toxicity, and possibly allowing physician's to individualize drug therapy to improve clinical response. Novel treatment strategies, including infliximab are being developed in Pediatrics with the aim at improving overall treatment efficacy and potentially avoid surgery.     

Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations

Ulcerative colitis (UC) and Crohn disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders that can affect the gastrointestinal tract of children and adults. Like other autoimmune processes, the cause(s) of these disorders remain unknown but likely involves some interplay between genetic vulnerability and environmental factors. Children, in particular with UC or CD, can present to their primary care providers with similar symptoms, including abdominal pain, diarrhea, weight loss, and bloody stool. Although UC and CD are more predominant in adults, epidemiologic studies have demonstrated that a significant percentage of these patients were diagnosed during childhood. The chronic nature of the inflammatory process observed in these children and the waxing and waning nature of their clinical symptoms can be especially disruptive to their physical, social, and academic development. As such, physicians caring for children must consider these diseases when evaluating patients with compatible symptoms. Recent research efforts have made available a variety of more specific and effective pharmacologic agents and improved endoscopic and radiologic assessment tools to assist clinicians in the diagnosis and interval assessment of their patients with IBD; however, as the level of complexity of these interventions has increased, so too has the need for practitioners to become familiar with a wider array of treatments and the risks and benefits of particular diagnostic testing. Nonetheless, in most cases, and especially when frequent visits to subspecialty referral centers are not geographically feasible, primary care providers can be active participants in the management of their pediatric patients with IBD. The goal of this article is to educate and assist pediatricians and adult gastroenterology physicians caring for children with IBD, and in doing so, help to develop more collaborative care plans between primary care and subspecialty providers.     

A Case of Ulcerative Colitis Induced by Oral Ferrous Sulfate

We report a case of ulcerative colitis (UC) in a 15 year old female undergoing treatment for anemia with oral ferrous sulfate. We suggest that the oral ferrous sulfate initiated the typical symptoms of UC in this case. This case is the first clinical report to our knowledge supporting the 'iron-catalysed oxidant-mediated ischemic injury theory' of UC.     

儿童溃疡性结肠炎172例

目的分析中国儿童溃疡性结肠炎（UC）患者的临床资料为其诊治提供帮助。方法采用CBM、CNKI及VIP数据库检索1995~2004年国内发表的儿童UC的文献,对符合纳入标准者及同期本院确诊UC患儿172例的临床特征、X线和内镜表现、组织学特点、治疗及预后进行分析。结果172例中男女之比是1.07：1.0;就诊年龄2个月~15岁,≤3岁36.7%;病程3d~4年;阳性家族史1例。儿童UC以慢性腹泻、黏液血便或脓血便、腹痛为主要表现,发热、体质量减低或营养不良、贫血等全身表现常见,肠外表现及并发症少见,病变范围以全结肠为主,病情以中重型居多。以水杨酸偶氮磺胺吡啶（SASP）或5-乙酰水杨酸（5-ASA）为基础,配合糖皮质激素治疗在短期内可获得临床缓解,但长时程随访完全缓解者不足1/3。结论婴幼儿UC患者并不少见,儿童UC临床特征有异于成人,3岁前后亦不尽相同。儿童UC误诊率高,治疗困难。制定一套适合中国儿童UC的诊疗规范十分必要。     

儿童溃疡性结肠炎的内镜检查和临床研究

目的 分析儿童溃疡性结肠炎的临床特征及其诊断。方法 对４０例儿童ＵＣ的内镜表现、组织学特点以及临床特征进行分析。结果 儿童ＵＣ占结肠镜检查总数的４％,２个月－１２岁,最小发病年龄生后７ｄ,中度＋重度占７５％（１８＋１２／４０）,临床表现慢性腹泻６８％（２７／４０）,粘液或粘液血便５３％（２１／４０）,反复便血４８％）１９／４０）,腹痛呕吐等不明显,营养不良有３０％（１２／４０）,贫血２８％（１１＝     

Incidence of inflammatory bowel disease in children in Brittany (1994-1997). Breton association of study and research on digestive system diseases (Abermad)]

BACKGROUND: The aim of this work was to determine in Brittany the incidence and main clinical pattern of inflammatory bowel disease (IBD) occurring during childhood. These data are compared to the previous epidemiologic data available from the Northern France registry or around the world. METHODS: Private and public Brittany gastroenterologists (2,836,418 inhabitants including 618,049 children under 17 years of age) referred all patients consulting for inflammatory bowel disease from January 1994 to December 1997. An interviewer-practitioner completed at the gastroenterologist's office a standard questionnaire for each patient. Each case was independently reviewed by four experts in a blind manner and made a final diagnosis of Crohn's disease (CD), ulcerative colitis (UC), or ulcerative proctitis and acute colitis (onset of symptoms < 6 weeks) or unclassified chronic colitis. RESULTS: Among 1,309 cases recorded, 88 were under 17 years of age (6.7%): 43 (49%) had CD (including three possible cases), 14 (16%) had UC (including three proctitis), 24 (27%) acute colitis and 7 (8%) unclassified chronic colitis. The crude mean annual incidence (per 100,000 children) based on definite and probable cases only was 2.5 for IBD, 1.6 for CD and 0.57 for UC, without variation between 1994 and 1997. The male/female ratio was 2.3 for CD and 1.3 for UC. The mean time between onset of disease and diagnosis was equal to 7.2 and 8.6 months for CD and UC respectively (median: 3 and 5 months). A familial history of IBD was present in 5 cases (8%). In CD, the small and large bowel were involved in 58% of patients, whereas an isolated involvement of small or large bowel occurred in 15% and 23% of cases. Among the 14 UC, there were three proctitis and four pancolitis. Among 43 CD, a granuloma was present in 48% of cases. CONCLUSIONS: In Brittany the incidence of CD and UC in childhood was similar to the published data from Northern France. Clinical presentation and symptoms were not different. However, the rate of acute colitis was higher and the accurate incidence of IBD could be underestimated, requiring a follow-up to classify these cases.     

Acute fulminant ulcerative colitis with toxic megacolon

An 11-year-old boy with acute fulminant ulcerative colitis (UC) is presented. He had systemic deterioration with frequent diarrhea and lethargy. Acute fulminant UC associated with toxic megacolon was diagnosed by rectal endoscopy and biopsied specimen. He was treated with intensive intravenous administration of prednisolone and total parenteral nutrition. He recovered completely without any surgical intervention.     

Infliximab is effective in acute but not chronic childhood ulcerative colitis

PURPOSE: The authors report their experience with infliximab in pediatric patients with ulcerative colitis (UC). METHODS: Fourteen patients were reviewed. Group 1 included five patients with newly diagnosed, fulminant colitis refractory to 7 to 10 days of intravenous steroids. Group 2 included four patients with ulcerative colitis in remission off steroid therapy who experienced relapse and were hospitalized with fulminant colitis refractory to intravenous steroids for 7 to 10 days. Group 3 included five patients chronically dependent on steroids with colitis refractory to medical management. All patients were treated on an open-label basis with infliximab infusions of 5 mg/kg/dose at 0, 2, and 6 weeks and every 6 to 8 weeks thereafter. Follow-up was maintained for at least 6 weeks. Clinical status was scored with the Lichtiger Colitis Activity Index (LCAI) at each visit. LCAI >or=10 was considered treatment failure. We defined success as LCAI or=11 before infliximab treatment. All group 1 patients experienced response to infliximab. All but one (75%) patient in group 2 had a response. Only one (20%) group 3 patient had a response to infliximab. CONCLUSION: Infliximab was an effective agent in the treatment of acute UC in our patients. Long-term steroid use and emergency colectomy were avoided. Infliximab was less effective in patients who were dependent on steroids.     

Infliximab in pediatric ulcerative colitis: two-year follow-up

OBJECTIVES: The role of infliximab in treating pediatric ulcerative colitis (UC) is not defined. The authors previously have described their experience with the open label use of infliximab in nine children with moderate to severe UC. The aim of this study was to describe the outcome of these patients after a minimum 2-year follow-up and to describe the responses of eight additional patients to this medication. METHODS: The authors reviewed all pediatric patients with UC who received infliximab at The Children's Hospital of Philadelphia from its first use until February 2003. Tolerance of the infusions and adverse events were recorded. RESULTS: Follow-up information for a minimum of 2 years was reviewed for the nine initial patients. A total of 73 infliximab infusions were administered to these patients. Seven of nine (78%) patients were considered to be responders to the initial dose of infliximab. Two of these patients became nonresponders within 9 months of the first dose of infliximab and underwent colectomy. Of the remaining five (56%) patients with sustained response, two continue to receive infliximab infusions and three are doing well without infliximab. One patient experienced an infusion reaction, and one experienced herpes zoster infection. We have treated eight additional UC patients with infliximab. Seven (88%) patients were considered responders. One responder experienced relapse within 2 months. Overall, a short-term improvement was seen in 14 of 17 (82%) patients, and sustained improvement in 10 of 16 (63%) patients followed up for more than 9 months. All five patients with severe or fulminant UC, unresponsive to 2 weeks of intravenous corticosteroid therapy, experienced improvement with infliximab. Infliximab was well tolerated. CONCLUSION: Infliximab is associated with short- and long-term clinical improvement in children and adolescents with moderate to severe UC.     

Sibling psychological status and style as related to the disease of their chronically ill brothers and sisters: implications for models of biopsychosocial interaction

This study explores the relationship between disease type and disease activity, and the psychological status of siblings of chronically ill children. Closest-age siblings of children with Crohn's disease (CD) (n = 41) and ulcerative colitis (UC) (n = 24) were assessed for psychological disorder and psychological style, using reliable and standardized measures. The disease activity of the patients was also evaluated. Assessment occurred during outpatient visits to a pediatric gastroenterology division. Results indicated that CD siblings had more psychological disorder than UC siblings. This was not due to greater acute disease activity in the CD patients. However, as a group, siblings of the sickest CD patients displayed more "internalizing" behaviors, whereas siblings of the healthiest CD patients displayed more "externalizing" behaviors. UC siblings, who were psychologically healthier, displayed "externalizing" behaviors regardless of the patient's disease activity. These results are in accord with our previous findings on family functioning, which, together, yield a heuristic model representing the different patterns of biopsychosocial interaction for CD in contrast to UC.