George Alex

Consensus for Managing Acute Severe Ulcerative Colitis in Children: A Systematic Review and Joint Statement From ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN

OBJECTIVES:Acute severe ulcerative colitis (ASC) is a potentially life-threatening disease. We aimed to formulate guidelines for managing ASC in children based on systematic review of the literature and robust consensus process. This manuscript is a product of a joint effort of the ECCO (European Crohns and Colitis Organization), the Pediatric Porto Inflammatory Bowel Disease (IBD) Working group of ESPGHAN (European Society of Pediatric Gastroenterology, Hepatology, and Nutrition) and ESPGHAN.METHODS:A group of 19 experts in pediatric IBD participated in an iterative consensus process including two face-to-face meetings. A total of 17 predefined questions were addressed by working subgroups based on a systematic review of the literature.RESULTS:The recommendations and practice points were eventually endorsed with a consensus rate of at least 95% regarding: definitions, initial evaluation, standard therapy, timing of second-line therapy, the role of endoscopic evaluation and heparin prophylaxis, how to administer second-line medical therapy, how to assess response, surgical considerations, and discharge recommendations. A management flowchart is presented based on daily scoring of the Pediatric Ulcerative Colitis Activity Index (PUCAI), along with 28 formal recommendations and 34 practice points.CONCLUSIONS:These guidelines provide clinically useful points to guide the management of ASC in children. Taken together, the recommendations offer a standardized protocol that allows effective monitoring of disease progress and timely treatment escalation when needed.

Sixty-year study of incidence of childhood ulcerative colitis finds eleven-fold increase beginning in 1990s.

Background:We sought to define the point at which a recently noted marked increase in the incidence of ulcerative colitis (UC) had occurred in children in Victoria, Australia. Methods:A 60-year retrospective review (1950-2009) of children age 16 years or less diagnosed with UC in the state’s major pediatric centers was performed. Results:In all, 342 children were diagnosed with UC (male to female ratio of 1.25:1.0, median age 10.9 years, interquartile range [IQR] 7.0, 13.2). The overall median annual incidence of UC was 0.36/105 children ⩽16 years of age (IQR 0.18, 0.66). The number of reported cases increased by 11-fold during the study period (P < 0.001). This marked increase appeared to occur from the early 1990s and has yet to plateau. Children diagnosed during the last two decades were older at diagnosis (median 10 years vs. 11.6, P < 0.0001), and had higher weight- and height-for-age z scores than those diagnosed during the first 40 years (mean weight-for-age [standard deviation] 1950−1989: −0.80 [1.56] vs. 1990–2009: −0.11 [1.17], P < 0.001; mean height-for-age 1950–1989: −0.50 [1.15] vs. 1990–2009: –0.13 [1.12], P < 0.05). More recently diagnosed children also had more extensive disease (1950–1989: 52% vs. 1990–2009: 71%, P < 0.01). Conclusions:The incidence of UC has increased markedly in Victorian children since 1990. Although some of this change may be attributable to earlier diagnosis, it is unlikely that this can provide a complete explanation for this still-increasing condition.

Perspectives of paediatric and adult gastroenterologists on transfer and transition care of adolescents with inflammatory bowel disease

Programmes specific to inflammatory bowel disease (IBD) that facilitate transition from paediatric to adult care are currently lacking.

Can Celiac Serology Alone be Used as a Marker of Duodenal Mucosal Recovery in Children with Celiac Disease on a Gluten-Free Diet?

OBJECTIVES:Assessment of treatment response in children with celiac disease (CD) after commencing a strict gluten-free diet (GFD) is generally based on the resolution of clinical features and normalization of serology. Recent adult studies have shown that serologic markers do not correlate with mucosal recovery. We aimed (i) to determine whether anti-tissue transglutaminase immunoglobulin (Ig)A (tTG) and anti-deamidated gliadin peptide IgG (DGP) antibodies are sensitive and specific markers of mucosal recovery in children with CD on a GFD for at least 12 months, and (ii) to determine whether a validated dietary questionnaire of compliance can identify patients with mucosal recovery.METHODS:A total of 150 children with biopsy-proven CD were prospectively evaluated with duodenal biopsies at ≥12 months on GFD, paired with repeat tTG and DGP serology. The biopsies were reviewed in a blinded manner by two histopathologists and graded by Marsh criteria. A validated questionnaire of dietary compliance was also administered.RESULTS:Of 150 children recruited, 27 (18%) had positive serology, 97 (65%) had negative serology, and 26 (17%) had equivocal serology. Of the 97 children with negative serology, none had Marsh type 3 enteropathy. Of the 27 patients with positive serology, only 6 had Marsh type 3 changes. The sensitivity and specificity of serology as a marker of significant mucosal pathology was 75 and 85%, respectively, with a positive predictive value of 22% but a negative predictive value of 98%. Of the 129 (86%) questionnaires completed, 88% reported good or excellent compliance with a GFD (negative predictive value 97%).CONCLUSIONS:This study suggests that follow-up using two serological tests in children with CD on a GFD may obviate the need for repeat mucosal biopsy in the majority of patients. A standardized dietary questionnaire may be useful in identifying patients who require further evaluation.

The use of biologic agents in pediatric inflammatory bowel disease.

Purpose of review Therapeutic options and approaches in inflammatory bowel disease (IBD) continue to evolve. This review will summarize the recent studies of treatment strategies, efficacy, safety and outcome of biological agents in the treatment of children with Crohns disease and ulcerative colitis. Recent findings Although there has been little recent change in the number of biologicals easily available for the treatment of children, usage has broadened in pediatric IBD and new treatment strategies have emerged. The use of biologicals in refractory pediatric ulcerative colitis is now accepted, with evidence supporting their potential for maintenance therapy. In pediatric Crohns disease, scheduled treatment regimens have shown superiority to episodic treatment. Although the ‘top-down’ approach with early use of biologicals produces superior remission rates in adults, there is still little evidence in children. Concomitant immunosuppression appears to reduce immunogenicity and improve therapeutic control, but there are added risks for infection and malignancy. Summary Biologicals now form an integral part of the treatment algorithm in childhood IBD and their use is likely to increase. Treatment regimens, particularly those involving concomitant immunosuppressants, need to take account of the perceptions of risk.

Mesenteric Castleman's disease in childhood

and rarely occurs in children. In 70% of cases, it occurs in the mediastinum. 3–5 The neck, retroperitoneum, pancreas, pelvic cavity and the axillary and inguinal lymph nodes are uncommon sites of involvement. 4,6 Furthermore the mesenteric Castleman’s disease is very rare. To our knowledge only 12 cases have been reported. 4,7–9 Surgical excision of the affected lymph node plays an important role in treatment of this disease. We encountered a case of the mesenteric Castleman’s disease in a paediatric surgical patient. Information from the literature research on this entity and the pathological findings are included in this report. An 8-year-old boy with no underlying health problems presented to his local doctor with symptoms of tonsillitis. Routine blood tests showed: hypochromic microcystic anaemia (haemoglobin level of 90 g/L), thrombocytosis (platelets count of 558 × 10 9 /L) and elevated erythrocyte sedimentation rate (ESR of 118 mm/h). His white cell count was normal. His iron study was difficult to interpret in the context of high acute inflammatory markers. The stool and the urine microscopy and culture were negative. His chest X-ray was normal. The patient did not have any symptoms or signs of chronic systemic infections, malignancy, gastrointestinal blood loss or malabsorption. His dietary history was satisfactory. He had a trial of 6 weeks iron replacement therapy in which he had no response to the treatment. Further investigations showed the presence of hypergammaglobulinaemia. However, tests for Coeliac disease were negative. He had a normal Meckels’ scan, and normal endoscopic studies of upper and lower gastrointestinal tracts. A small bowel barium series did not reveal Crohn’s disease of the small bowel or a duplication cyst. However, it revealed a mass of 4 × 5 cm displacing between the loops of bowel. Subsequent ultrasound imaging showed a well circumscribed 5-cm mass with heterogeneous echogenicity at the level of the bifurcation of the aorta. He was referred to the paediatric surgical clinic for the evaluation of this mass. The patient underwent laparotomy and a 4 × 5cm irregular yellow-tan ovoid solid mass arising from ileal mesentery was resected. Histology of the mass showed a lymph node consisting of a large number of lymphoid follicles with germinal centres separated by bands of dense hyaline connective tissue. Numerous plasma cells were present (Fig. 1). Only occasional vessels with a thick hyaline wall are seen in the germinal centres. The features are consistent with Castleman’s disease of the plasma cell type. The patient had an unremarkable recovery postoperatively. His anaemia, platelets count, inflammatory markers and immunoglobulin level improved at the 3-month follow up.

Clinical Patterns and Outcome of Early-Onset Inflammatory Bowel Disease

ABSTRACT We sought to determine whether extremely-early-onset childhood inflammatory bowel disease (age <6 years; 20 ulcerative colitis [UC], 8 Crohn disease [CD], 2 indeterminate, sequentially diagnosed) was clinically more severe than in older children (6–17 years; 19 UC, 39 CD, 2 indeterminate). Early-onset UC was marked by less abdominal pain at presentation, but an aggressive course with a significant reduction in weight-for-age, increased use of immunosuppressants, and more surgery. Children with early-onset CD were more likely to have bloody stools at presentation and an isolated colitis. This study supports the suggestion that inflammatory bowel disease phenotype differs in early-onset disease.

Drug rash with eosinophilia and systemic symptoms secondary to sulfasalazine

A severe cutaneous eruption in an unwell patient can be a major cause of physician anxiety. With numerous differential diagnoses, an early accurate diagnosis can be challenging. infectious causes are the most important to exclude in a timely manner and drug rash and eosinophilia with systemic symptoms (DRESS) is another differential diagnosis that should be considered in children. This hypersensitivity reaction is associated with multisystem involvement. Children with underlying chronic diseases may have impairment of normal metabolic pathways and are also often on multiple medications. Therefore, drugs should always be considered in the aetiopathology of any new symptoms and signs. This case report informs readers of the association of sulfasalazine and DRESS in an 11‐year‐old with inflammatory bowel disease and discusses its pathogenesis and treatment. Increased awareness of this disorder will hopefully lead to increased reporting and consequently illuminate the syndrome more clearly and help guide its prevention and treatment.

Hepatitis C infection in children: a Melbourne perspective.

Objective: To examine the clinical spectrum of hepatitis C virus (HCV) infected children in our care by determining presentation, mode of acquisition, degree of co‐infection, biochemical evidence of persisting hepatitis and treatment outcome.

Immune response to pandemic H1N1 2009 influenza a vaccination in pediatric liver transplant recipients.

After the announcement of a worldwide pandemic in June 2009, a single dose of a monovalent pandemic H1N1 2009 influenza A (pH1N1/09) vaccine was advocated for all Australians who were 10 years and older because of excellent immunogenicity trial results for healthy children and adults. Immunocompromised patients have previously been shown to have lower seroconversion rates after routine vaccinations. There is a lack of data concerning the immune response of this patient group after pH1N1/09 vaccination. The aim of this study was to assess the immunogenicity of a pH1N1/09 vaccine in pediatric liver transplant recipients 10 years of age or older. Liver transplant recipients ≥ 10 years were prospectively recruited. All participants were administered a single intramuscular injection of the pH1N1/09 vaccine (15 μg). Serum antibody levels were determined by hemagglutination immediately before and ≥ 6 weeks after vaccination. Clinical and laboratory data (age, time since transplantation, immunosuppression, and lymphocyte counts) were analyzed comparing seroconverters and nonconverters with the Students t test. A second dose of the vaccine was offered to all those who displayed no seroprotective titers after the first vaccination. Antibody levels were again determined 6 weeks later. Twenty‐one of 28 liver transplant patients completed the study. The seroconversion rate was 62% after the first dose and 89.5% after the second dose. At baseline, 7 of 21 patients (33.4%) were already seropositive. Increasing time since transplantation positively correlated with successful seroconversion. In conclusion, a single dose of a pandemic influenza A vaccine does not elicit a reliable immune response in adolescent pediatric liver transplant patients. A second dose of the vaccine is warranted in this group of patients, at least in a pandemic scenario. There is an urgent need to further assess vaccine strategies in this high‐risk group. Liver Transpl 17:914–920, 2011.