儿童炎症性肠病治疗现状和进展

炎症性肠病是一种多因素的肠道慢性炎症性疾病,主要分为溃疡性结肠炎、克罗恩病和未定型炎症性肠病.炎症性肠病的发病率逐年增加,并且呈现低龄化的趋势,儿童炎症性肠病越来越普遍.由于儿童正处于生长发育较快的特殊时期,导致儿童炎症性肠病与成人在临床表现、疾病类型、治疗方案、并发症等问题上有很多不同.该文对炎症性肠病尤其是儿童炎症性肠病的治疗现状和进展进行阐述.     

儿童炎症性肠病预后预测模型研究进展

炎症性肠病主要包括克罗恩病和溃疡性结肠炎。部分炎症性肠病由单基因缺陷引起,起病年龄早,呈现出与上述疾病亚型不同的预后特点。对个体预后的精准预测将有助于风险分层,指导治疗。现从克罗恩病、溃疡性结肠炎和单基因炎症性肠病3个角度,对儿童炎症性肠病预后预测模型进行综述,以期指导儿童炎症性肠病的预后评估。     

炎症性肠病的诊断和治疗进展

世界胃肠组织于2010年提出新的炎症性肠病的诊疗指南,提出了规范化的及部分适合儿科的诊疗意见。炎症性肠病中溃疡性结肠炎及Crohn’s病的分类、活动度评估有助于治疗方案的选择,提出个性化治疗。通过了解近年国外对儿童炎症性肠病药物治疗短期、长期疗效进行的多中心前瞻性研究,为临床医师的选药及临床咨询提供参考。     

儿童炎症性肠病30例临床分析

儿童炎症性肠病(inflammatory bowel disease,IBD)指病因不明的一组非特异性肠道炎症性疾病。主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn′s disease,CD),UC和CD在儿童中发病率较低,国内相关病例报道较少。本文对自1993年6月至2006年12月本科收治的病例进行     

极早发型炎症性肠病的特点与治疗

炎症性肠病（IBD）是一种病因不明的慢性非特异性肠道炎症性疾病。该疾病包括3种主要类型：克罗恩病（CD）、溃疡性结肠炎（UC）和未分型IBD（IBD-U）。IBD在成人中发病率高，但近年来，IBD在儿童中发病率越来越高。极早发型IBD（VEO-IBD）是儿童IBD的一部分，有其独特的表型和遗传学特征，通常病情严重，并且对常规IBD治疗效果差。该文对VEO-IBD的临床特点、发病机制和治疗进行了综述。     

炎症性肠病患儿对英夫利昔单克隆抗体治疗失应答的影响因素研究进展

炎症性肠病(IBD)是包括克罗恩病、溃疡性结肠炎和未定型结肠炎在内的一组病因不明的慢性非特异性胃肠道炎症性疾病。近年来儿童IBD的发病率逐年增加, 对患儿、家庭及社会造成了相当大的疾病负担。英夫利昔单克隆抗体(IFX)作为一种有效的重要治疗方法, 近年来临床上对其出现失应答的IBD患儿逐渐增多, 其原因复杂且不明确。本文将对可能导致IBD患儿对IFX治疗出现失应答的因素进行讨论和归纳, 以期寻找合适的方法提高IFX对IBD患儿的治疗效果。     

炎症性肠病与claudin蛋白

炎症性肠病（inflammatory bowel disease,IBD）包括溃疡性结肠炎（ulcerative colitis,UC）、克罗思病(Crohn's disease,CD),儿童IBD的发病率为(2.2～6.8 )/100 000[1]。IBD病程迁延,反复腹泻以及吸收功能紊乱影响患儿生长发育,降低患儿的生活质量[2]。急性炎症和慢性肠黏膜病变导致肠黏膜屏障损伤,是腹泻发作的重要原因[3]。     

肠道菌群与儿科肠道炎症性疾病研究进展

新生儿坏死性小肠结肠炎(NEC)、儿童炎症性肠病(IBD)及先天性巨结肠合并小肠结肠炎(HAEC)等是儿科较常见的、严重影响患儿生活质量甚至威胁生命的肠道炎症性疾病。目前其发病机制尚不明确。研究表明,肠道炎症性疾病与肠道菌群紊乱有密切关系,但约85%的肠道细菌无法由培养得到。近年来高通量测序技术的迅速发展,使全面深入探究肠道微生物群落成为可能。文章综述近年来肠道菌群在儿科肠道炎症性疾病发病中的作用及益生菌应用的研究进展。     

肠内营养治疗儿童炎症性肠病机制研究进展

正炎症性肠病(inflammatory bowel disease,IBD)是一种主要累及消化道的慢性肠道非特异性炎症性疾病,临床常见溃疡性结肠炎(ulcerative colitis,UC)、克罗恩病(Crohn’s disease,CD)及未定型结肠炎。IBD在我国的年总发病率为1.96/100 000~([1]),儿童群体年发病率为0.55/100 000~([2]),有逐年增加趋势,尤以早发型UC为主。肠内营养(enteral nutrition,EN)作为IBD的新兴治疗方案,其疗效已被     

肠内营养在儿童炎症性肠病中的应用

<正>炎症性肠病(inflammatory bowel diseases,IBD)是一种主要累及消化道的病因不明的慢性肠道非特异性炎症性疾病,临床常见溃疡性结肠炎(ul-cerative colitis,UC)、克罗恩病(Crohn’s disease,CD)及未定型结肠炎。儿童IBD发病率最高的是欧洲23/10万人年,亚洲、中东和大洋洲发病率为11.4/10万人年~([1]),而国内儿童IBD的发病率也在逐年上升,已引起了临床医生的高度关注。     

Incidence, clinical presentation and location at diagnosis of pediatric inflammatory bowel disease: a prospective population-based study in northern France (1988-1999)

OBJECTIVE: To assess the incidence and location at diagnosis of inflammatory bowel disease in children and adolescents in northern France between 1988 and 1999. METHODS: A 12-year prospective population-based study was conducted by gastroenterologists and pediatric gastroenterologists of northern France (1,312,141 children <17 years of age). RESULTS: From 1988 to 1999, 509 cases of childhood inflammatory bowel disease were recorded (7.2% of all inflammatory bowel disease cases in Northern France): 367 Crohn disease, 122 ulcerative colitis and 20 indeterminate colitis. The mean standardized incidence was 3.1/10(5) for inflammatory bowel disease as a whole (2.3 for Crohn disease, 0.8 for ulcerative colitis and 0.12 for indeterminate colitis). Crohn disease location at diagnosis was: small bowel and colon (71%), colon only (10%) and small bowel only (19%). Location of initial ulcerative colitis was: proctitis (11%), left colitis (57%) and pancolitis (32%). Although ulcerative colitis incidence remained stable (0.8), Crohn disease incidence increased from 2.1 in 1988 to 1990 to 2.6 in 1997 to 1999 (P = 0.2). CONCLUSIONS: The incidence of Crohn disease in the children of northern France showed an increasing trend (20%; not significant) during the 12-year period while the incidence of ulcerative colitis remained stable. In the entire population(children and adults)the incidence of Crohn disease increased significantly (+23%; P < 0.001), while the incidence of ulcerative colitis decreased (-17%; P < 0.0001).     

Incidence and prevalence of inflammatory bowel disease in children in South-Western Sweden

Hildebrand H, Brydolf M, Holmquist L, Krantz I, Kristiansson B. Incidence and prevalence of inflammatory bowel disease in children in South-Western Sweden Acta PEdiatr 1994;83:640–5. Stockholm. ISSN 0803–5253
The incidence and prevalence of inflammatory bowel disease were estimated in all children less than 16 years of age living in the city of Göteborg and in three counties in South-Western Sweden, from 1983 to 1987. One hundred and thirty-two patients were classified according to set criteria into one of four diagnostic categories: ulcerative colitis, Crohn's disease, probable Crohn's disease and indeterminate colitis. The crude incidence of inflammatory bowel disease was 5.3 per 100 000 children per year and the prevalence 21.5 per 100000 children. This study lends support to the hypothesis that Crohn's disease has increased among Swedish children. Crohn's disease now appears to be at least as common as ulcerative colitis. Thirty-five of 55 patients first classified as indeterminate colitis or probable Crohn's disease later fulfilled the criteria of ulcerative colitis or Crohn's disease during a mean follow-up period of 4.6 years. This study emphasizes the importance, in epidemiological studies of inflammatory bowel disease, of inciuding those cases where a definite diagnosis of ulcerative colitis or Crohn's disease cannot be established initially and of re-evaluating the initial diagnosis regularly.     

Fecal calprotectin: validation as a noninvasive measure of bowel inflammation in childhood inflammatory bowel disease

BACKGROUND: Calprotectin is an abundant neutrophil protein, which is extremely stable in feces. This study aimed to validate fecal calprotectin as a marker of bowel inflammation against invasive measures in children with inflammatory bowel disease (IBD), including colitis and small bowel Crohn disease. METHODS: Fecal calprotectin was measured using a simple enzyme-linked immunosorbent assay in 36 spot stool samples from 22 children before colonoscopy and from 14 children before technetium-99 (99Tc) scanning. Using standard scoring systems, the severity of inflammation was assessed macroscopically and histologically at six standard sites in those who underwent colonoscopy and also at six standard sites in those who underwent 99Tc scanning. The subscores from each site were summated to give combined severity and extent scores for macroscopic and for histologic inflammation in the group undergoing colonoscopy and total inflammation in the group undergoing 99Tc scanning. RESULTS: In the 22 children who underwent colonoscopy, median fecal calprotectin was 4.9 mg/L (0.1-272.5 mg/L) (range). Disease groups included six normal cases, nine ulcerative colitis cases, two isolated Crohn colitis cases, two indeterminate colitis cases, and three allergic colitis cases. Fecal calprotectin correlated closely with colonic macroscopic inflammation (r = 0.75, P < 0.001) and histologic inflammation (r = 0.85, P < 0.001). Of the 14 children undergoing 99Tc scanning, 10 had Crohn disease, 3 had ulcerative colitis, and 1 had allergic colitis. Median fecal calprotectin was 9.1 mg/L (0.3-141.7 mg/L), and this correlated closely with the 99Tc scanning score (r = 0.80, P = 0.001). CONCLUSION: Fecal calprotectin correlates closely with the best invasive measures of colonic and small bowel inflammation in childhood inflammatory bowel disease. As a sensitive objective measure of bowel inflammation that is risk-free and noninvasive, fecal calprotectin lends itself particularly to the monitoring of and assessment of therapeutic interventions in children with inflammatory bowel disease.     

Tumor necrosis factor-alpha is not elevated in children with inflammatory bowel disease

Chronic undernutrition and high-dose daily corticosteroid therapy are well-accepted causes of growth failure in children with inflammatory bowel disease. Occasionally, children are seen with minimal gastrointestinal symptoms but in whom severe anorexia and profound growth impairment are evident. Recent observations that elevated serum levels of tumor necrosis factor-alpha (TNF) in cachexia associated with a number of disease states have suggested a similar possible role in inflammatory bowel disease. Accordingly, we determined TNF levels in 45 children and adolescents with inflammatory bowel disease (18 ulcerative colitis, 27 Crohn's disease) at varying times during their clinical course and compared them to values obtained from a group of 25 children with functional bowel disease. No differences were noted in serum TNF levels between the children with inflammatory bowel disease and the control population. Values were generally within the range of the lower limit of detection of the assay. In the children with inflammatory bowel disease, there was no significant correlation between TNF levels and disease activity or growth parameters. Our observations suggest that elevated TNF levels are not associated with inflammatory bowel disease in children.     

Long-term outcome of inflammatory bowel disease—Unclassified in children

Objectives

To document the frequency at diagnosis and evolution over time of inflammatory bowel disease-unclassified in children.

Methods

Analysis of case records (2004–2011) of patients diagnosed with inflammatory bowel disease-unclassified following uppergastrointestinal endoscopy, ileocolonoscopy and small bowel imaging. Any subsequent diagnostic reclassification by 2016 was recorded.

Results

344 children diagnosed as inflammatory bowel disease: 58% Crohn’s disease, 34.5% ulcerative colitis, and 7.5% (n=26) inflammatory bowel disease-unclassified. 25/26 inflammatory bowel disease-unclassified patients were followed for 4.5–11.5 years. 17 of these patients needed endoscopic reevaluation leading to changed diagnosis in ten (Crohn’s disease 7, ulcerative colitis 3).

Conclusion

7.5% (25/344) of inflammatory bowel disease children had inflammatory bowel disease-unclassified at diagnosis; 10 (40%) evolved into Crohn’s disease or ulcerative colitis.

     

Asymptomatic transient uveitis in children with inflammatory bowel disease.

Although acute anterior uveitis has been noted in children with inflammatory bowel disease, it has not been appreciated in the absence of ocular symptoms. To determine the presence of asymptomatic uveitis, slit-lamp examinations were performed in 19 children with granulomatous bowel disease and seven with ulcerative colitis. In the former group, six had uveitis, while no abnormalities were noted in those with ulcerative colitis. Abnormalities consisted of cells and flare in the anterior chamber. In the group with asymptomatic uveitis, all were male, three were black, and all had colonic involvement. No positive correlations were noted between the presence of uveitis and bowel symptoms, duration of illness, extraintestinal manifestations, or specific treatment regimens. None of the six children with uveitis had evidence of spondylitis, and five were HLA-B27-negative. Repeated eye examinations six to 12 months later disclosed no evidence of uveitis in four of five children and improvement in the remaining child. These data suggest that asymptomatic transient uveitis is common in children with granulomatous bowel disease, but progression to severe adult uveal disease remains unclear.     

Magnetic resonance imaging to distinguish the type and severity of pediatric inflammatory bowel diseases

BACKGROUND: The distinction between ulcerative colitis and Crohn's disease is important, because treatment options and clinical course may vary. Magnetic resonance imaging (MRI) allows noninvasive transmural assessment of the intestine and may facilitate differentiation of ulcerative colitis from Crohn's disease. The objective of this prospective study was to determine whether MRI differentiates Crohn's disease from ulcerative colitis in children as effectively as colonoscopy with mucosal biopsies. METHODS: Fifteen patients underwent colonoscopy with biopsies followed by abdominal MRI. The MRI diagnosis, determined by two radiologists independently completing a standardized form was compared with the gastroenterologic diagnosis. RESULTS: After colonoscopy and review of histology, Crohn's disease was diagnosed in nine patients, ulcerative colitis in five, and indeterminate colitis in one, who was excluded from study. Agreement of the MRI diagnosis with the gastroenterologic diagnosis was 4 of 4 (100%) for ulcerative colitis, 4 of 10 (40%) for Crohn's disease considering both radiologists, and 5 of 10 (50%) for Crohn's disease for each radiologist individually. Percentage of enhancement by MRI did not correlate with the severity of inflammation determined at endoscopy among the patients with Crohn's disease (r = -0.3, P = 0.366). There was agreement on severity of inflammation in three of four patients with ulcerative colitis. CONCLUSIONS: Current MRI interpretation of inflammatory bowel disease did not adequately recognize Crohn's disease in children. Therefore, colonoscopy with biopsy remains the most accurate tool for determining the type and severity of inflammatory bowel disease in children and adolescents.     

The role of esophagogastroduodenoscopy in the initial evaluation of childhood inflammatory bowel disease: a 7-year study

OBJECTIVES: To assess the role of esophagogastroduodenoscopy in the evaluation of children with suspected inflammatory bowel disease. METHODS: All children with inflammatory bowel disease who underwent esophagogastroduodenoscopy during their initial evaluation at our institution during a 7-year period (December 1993 to November 2000) were included in the study. RESULTS: The study included 115 patients: 81 with Crohn disease (mean age, 11.34 years; 42 males) and 34 with ulcerative colitis (mean age, 11.79 years; 20 males). Abnormal findings on esophagogastroduodenoscopy were noted in 64% of patients with Crohn disease and 50% of children with ulcerative colitis; histologic abnormalities were found in 81.6% and 70.6% of the patients, respectively. Granulomas were found in the upper gastrointestinal tracts of 23 of 81 patients (28.4%), with the most common site being the gastric mucosa. Nine of these 23 patients had granulomas solely in the upper gastrointestinal tract. Additional unsuspected pathology noted included: candidiasis, hiatal hernia, Helicobacter pylori infection, and giardiasis. CONCLUSIONS: Endoscopic and histologic abnormalities were found in the upper gastrointestinal tracts of a significant number of children with inflammatory bowel disease. While the mechanism(s) underlying these abnormalities in patients with ulcerative colitis is unclear, the pathology can contribute to the patient's clinical condition. Pathology in the upper gastrointestinal tract should not exclude a diagnosis of ulcerative colitis. Granulomas, confirming the diagnosis of Crohn disease, were found in the upper gastrointestinal tracts of 28% of our patients with Crohn disease. In some cases, granulomas were found solely in the upper gastrointestinal tracts. Based on our data, esophagogastroduodenoscopy with biopsy should be performed in all pediatric patients with suspected inflammatory bowel disease.     

Use of C-reactive protein in children with newly diagnosed inflammatory bowel disease

C-reactive protein (CRP), a marker for inflammation, was evaluated with other routine blood tests in children with newly diagnosed inflammatory bowel disease. Evaluation of CRP level helped identify additional patients found to have inflammatory bowel disease at endoscopy, although a sizeable number of patients with mild ulcerative colitis had a normal CRP level.