Very early onset inflammatory bowel disease

Very early onset inflammatory bowel disease (VEO-IBD) represents a unique and growing subset of patients with inflammatory bowel disease (IBD). Some VEO-IBD patients present with immunodeficiency and possess loss of function genetic mutations involving immune pathways that cause their IBD. A search for Mendelian causes of IBD is likely most beneficial when the presentation involves extra-intestinal autoimmunity or involves intestinal histopathology that is atypical for IBD. While a subset of these young patients will have highly aggressive courses (and likely present with immunodeficiency), the majority of patients with VEO-IBD appear to have disease courses similar to that of their older counterparts. Most notably, many of these young children will require long courses of immunosuppression simply as a result of the profoundly early presentation—thus increasing their long-term risks of cancer and opportunistic infections.     

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。     

Clustering of (auto)immune diseases with early-onset and complicated inflammatory bowel disease

Studies in adult inflammatory bowel disease (IBD) patients have highlighted associations with genetic and serologic markers and suggest an association with disease location, behaviour and natural history. Data on patients with Crohn’s disease (CD, n = 80), ulcerative colitis (UC, n = 15) and indeterminate colitis (n = 4) were collected. All individuals were analysed for CARD15 R702W, G908R and L1007fs for toll-like receptor 4 (TLR4) Asp299Gly and for anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmatic antibodies (pANCA). After a mean of 10.7 years of follow up, the disease behaviour changed in 45% of CD patients, in contrast to disease location, where only 12.5% had a change (p < 0.001). The younger the age at diagnosis, the more patients presented with colonic disease (p = 0.021). Also, more TLR4 Asp299 Gly variants were found when the age at onset was younger (p = 0.018). A large number of concomitant diseases were observed. There was no difference in the prevalence of TLR4 variants nor ASCA or pANCA between the patients with or without concomitant diseases. Patients who progressed more often needed surgery as compared to patients who remained free of stenosing or fistulising disease (27/32 or 84% versus 3/35 or 8.6%, respectively, p < 0.0001) and more often had concomitant immune-mediated diseases and a trend for more seroreactivity towards ASCA.     

NOD2/CARD15 mutation analysis and genotype-phenotype correlation in Jewish pediatric patients compared with adults with Crohn's disease

OBJECTIVES: The allelic variants in the NOD2/CARD15 gene G908R, R702W, and 1007fs are strongly and independently associated with susceptibility to Crohn's disease (CD). Our aim was to compare the NOD2/CARD15 genotype and the genotype-phenotype correlation in Jewish pediatric patients with CD (相似文献   

儿童炎症性肠病病因及发病机制研究进展

<正>炎症性肠病(inflammatory bowel disease,IBD)是一种病因尚不明确的慢性非特异性肠道炎症性疾病,可累及回肠、直肠、结肠甚至全消化道,包括溃疡性结肠炎(ulcerative colitis,UC)、克罗恩病(Crohn disease,CD)和一类分类不明确的未确定型肠炎(IBD-unclassified,IBD-U)。近年来,儿童IBD发病率呈上升趋势[1-3]。儿童IBD不仅可引起腹痛、腹泻、便血及肠道外症状,甚至可引起生长发育障碍及精神状态改变。尽管IBD病因及发病机制暂未明     

IBD and IBD mimicking enterocolitis in children younger than 2 years of age

Inflammatory bowel disease (IBD) is uncommon in children younger than 2 years of age. The criteria for differentiating IBD from other diseases with similar clinical presentation is unclear. We describe 16 patients who, between 1984 and 2004, received a histological diagnosis of IBD during the first two years of life. Six patients presented with histological Crohn’s disease, eight with ulcerative colitis and two with indeterminate colitis. The median age at diagnosis was 125 days (range 1 day to 18 months) and the medium follow up was 89 months (range 65 days to 20 years). The disease appeared to be very severe: four children (25%) underwent total parenteral nutrition (TPN), two received colectomy (12.5%) and three patients died. Many of the patients required an aggressive, multidrug, immunosuppressive approach (azathioprine [AZA], Infliximab, thalidomide, cyclosporine A). One child presented with a hypogammaglobulinaemia without any specific immunodeficiency, while in the other patients, Wiskott-Aldrich syndrome (WAS) (4 cases) and chronic granulomatous disease (CGD) (2 cases) were identified. In 6/16 cases, allergic colitis was first considered; these cases initially underwent cow’s milk protein-free diet as the only therapy before IBD was finally diagnosed. In conclusion, early IBD has a severe prognosis and often needs an aggressive therapeutic approach. Furthermore, an improper diagnosis of allergic colitis might cause an important diagnostic delay. Some severe immunodeficiencies, such as WAS and CGD, may represent a problem in terms of differential diagnosis and might be wrongly diagnosed as very early onset IBD.     

Vitamin E supplementation improves neutropenia and reduces the frequency of infections in patients with glycogen storage disease type 1b

Background  Neutropenia and/or neutrophil dysfunction are part of glycogen storage disease type 1b (GSD1b) phenotype. Recent studies indicated that activation of apoptosis and increased reactive oxygen species are implicated in the pathogenesis of neutropenia in GSD1b. Methods  We studied seven GSD1b patients over a 2-year-period to evaluate the efficacy of vitamin E, a known antioxidant, in preventing or improving the clinical manifestations associated with neutropenia and neutrophil dysfunction. Frequency and severity of infections, neutrophil counts and function, ileocolonoscopy and intestinal histology, were monitored. During the first year, patients did not assume vitamin E; during the second year of the study, vitamin E supplementation was added to their therapeutic regimens. Results  During vitamin E supplementation, the mean values of neutrophil counts were significantly higher (p < 0.05) and neutrophil counts lower than 500/mm³ were found less frequently (p < 0.05); the frequency and severity of infections, mouth ulcers and perianal lesions, was reduced (p < 0.05); ileocolonoscopy and histology showed a mild improvement. Vitamin E supplementation did not result in changes in neutrophil function. Conclusions  These results suggest that vitamin E supplementation might be beneficial in GSD1b patients and may alleviate disease manifestations associated with neutropenia.     

Epstein-Barr virus-associated post-transplant lymphoproliferative disease after bone marrow transplantation mimicking graft-versus-host disease

In contrast to solid organ transplantation (Tx), the incidence of post-transplant lymphoproliferative disease (PTLD) after hematopoietic stem cell Tx (HSCT) is generally low. This risk, however, is significantly elevated in patients receiving human leukocyte antigen (HLA) mis-matched or T-cell-depleted grafts, or after treatment for severe graft-versus-host disease (GvHD). An 18-yr-old patient with positive Epstein-Barr virus (EBV) serology received a fully matched, unmanipulated bone marrow graft from an unrelated EBV-positive donor for treatment of acute myeloid leukemia (AML) in second complete remission. GvHD prophylaxis was performed with cyclosporin A (CsA) and a short course of methotrexate. Four months after Tx, the patient developed ulcerative tonsillitis that was unresponsive to antibiotic treatment. Diarrhea appearing simultaneously was interpreted as gastrointestinal GvHD and steroids were added to CsA. A few days later the patient was admitted to hospital because of generalized seizure and pneumonia. Despite reduction of immunosuppression, intensification of anti-viral treatment, and subsequent mechanical ventilation, the patient died of acute respiratory distress 6 days later. Autopsy demonstrated disseminated EBV-induced, multi-nodular lymphoma infiltration of the entire colon but no signs of GvHD. Moreover, both lungs, paratracheal lymph nodes, kidneys, thyroid gland, and liver were infiltrated with large B-cell non-Hodgkin's lymphomas. This case underlines the rapid and aggressive course of EBV-induced disseminated PTLD after HSCT, initially mimicking intestinal GvHD because of massive colonic lymphoma infiltration. Tissue biopsies should be performed early for establishing correct diagnosis, thus enabling specific therapy, e.g. infusion of donor leukocytes with cytotoxic T-lymphocytes.     

Castleman disease in a child with short stature

We report a 14‐year‐old boy with Castleman disease in this article. He complained of short stature, and his body height was 133.8 cm (<3rd percentile; z score ?4.5). There was marked delay in the appearance of secondary sexual characteristics. He was found to have a remittent fever and a lower mid‐abdominal tumor. Blood test revealed microcytic hypochromic anemia, thrombocytosis, polyclonal hypergammaglobulinemia, hyperfibrinogenemia, and elevated erythrocyte sedimentation rate. The serum IL‐6 and C‐reactive protein levels were increased. The mass was found to be mixed hyaline vascular and plasma cell type of Castleman disease through a pathological examination. Lymph nodes affected by Castleman disease cause overproduction of IL‐6. It decreases IGF‐1, IGFBP‐3 and serum testosterone levels. As a result of tumorectomy, his short stature and delay in the development of secondary sexual characteristics were improved.     

Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study

OBJECTIVE: To define epidemiologic and clinical characteristics of newly diagnosed pediatric inflammatory bowel disease (IBD) in a large population-based model. STUDY DESIGN: All pediatric gastroenterologists providing care for Wisconsin children voluntarily identified all new cases of IBD during a 2-year period. Demographic and clinical data were sent to a central registry prospectively for analysis. RESULTS: The incidence of IBD in Wisconsin children was 7.05 per 100,000, whereas the incidence for Crohn's disease was 4.56, more than twice the rate of ulcerative colitis (2.14). An equal IBD incidence occurred among all ethnic groups, and children from sparsely and densely populated counties were equally affected. The majority (89%) of new IBD diagnoses were nonfamilial. CONCLUSIONS: This study provides novel, prospective, and comprehensive information on pediatric IBD incidence within the United States. The surprisingly high incidence of pediatric IBD, the predominance of Crohn's disease over ulcerative colitis, the low frequency of patients with a family history, the equal distribution of IBD among all racial and ethnic groups, and the lack of a modulatory effect of urbanization on IBD incidence collectively suggest that the clinical spectrum of IBD is still evolving and point to environmental factors contributing to the pathogenesis.     

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.     

Acute lymphoblastic leukemia in a girl with Wilson's disease

Wilson's disease (WD) is an autosomal recessive defect in cellular copper transportation. Although acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy, only two cases of ALL associated with WD have been reported to date. One patient died of relapse and infection, and the other died of neutropenic sepsis during the treatment. We here describe the case of a 10‐year‐old girl with WD and ALL. Adverse events of chemotherapy, including liver toxicity and severe myelosuppression, necessitated adjustments in the chemotherapy doses. After completion of the treatment, the patient has remained in remission from ALL without progression of liver damage for 2 years. Severe treatment‐related toxicity should be considered in chemotherapy for patients with WD.     

Acute graft-versus-host disease of the heart

Graft-versus-host disease (GVHD) is a frequent cause of morbidity and mortality after bone marrow transplantation. Acute GVHD most commonly involves the skin, gastrointestinal tract, and liver. Involvement of other organ systems is rare and remains controversial. We report a patient with GVHD who suffered a fatal ventricular arrhythmia shortly after bone marrow transplantation. Autopsy of the heart showed lymphocyte infiltration. Investigations for cardiotrophic viruses were negative, and chimerism analysis of the heart showed both donor and recipient DNA. We conclude that the cause of death was possibly graft-versus-host disease of the heart. A review of the literature revealed a total of 14 cases of possible cardiac GVHD. All but one of the reported cases have occurred in pediatric patients and six of those patients died, suggesting that this may be a rare but frequently fatal complication of pediatric allogeneic stem cell transplant.     

Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry

OBJECTIVE: To determine the characteristics of inflammatory bowel disease (IBD) in young patients. STUDY DESIGN: Uniform data were collected from a cohort of patients with IBD who were enrolled from January 2000 to November 2002 at six pediatric centers (Pediatric IBD Consortium). RESULTS: Of 1370 children in the registry, the mean age at IBD diagnosis was 10.3 +/- 4.4 years; 54% were male, and 86% were white. Diagnosis was confirmed in 87 (6.1%) under 3 years of age, 211 (15.4%) before 6 years, 654 (47.7%) at 6 to 12 years, and 505 (36.9%) at 13 to 17 years. More than 63% of children younger than 8 years of age had isolated colonic disease, whether Crohn disease, ulcerative colitis (UC), or indeterminate colitis. Conversely, only 35% of those 8 years of age or older had isolated colonic disease ( P < .0001). Overall, 29% had one or more family members with IBD. The subgroup of children younger than 3 years of age with UC had the highest prevalence of first-degree relatives with IBD (44%). CONCLUSIONS: This demographically diverse pediatric IBD cohort revealed age-related variation in the distribution of IBD phenotype, with a high prevalence of isolated colonic disease in young children. Positive family history was especially common in young patients with UC.