Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease.

BACKGROUND: There is growing support for a biopsy avoidant approach to diagnose coeliac disease in both children and adults, using a serological diagnosis instead. AIMS: To assess the diagnostic accuracy of serological tests for coeliac disease in adults and children. METHODS: Seven electronic databases were searched between January 1990 and August 2020. Eligible diagnostic studies evaluated the accuracy of serological tests for coeliac disease against duodenal biopsy. Risk of bias assessment was performed using QUADAS-2. Bivariate random-effects meta-analyses were used to estimate serology sensitivity and specificity at the most commonly reported thresholds. RESULTS: 113 studies (n = 28,338) were included, all in secondary care populations. A subset of studies were included in meta-analyses due to variations in diagnostic thresholds. Summary sensitivity and specificity of immunoglobulin A (IgA) anti-tissue transglutaminase were 90.7% (95% confidence interval: 87.3%, 93.2%) and 87.4% (84.4%, 90.0%) in adults (5 studies) and 97.7% (91.0%, 99.4%) and 70.2% (39.3%, 89.6%) in children (6 studies); and of IgA endomysial antibodies were 88.0% (75.2%, 94.7%) and 99.6% (92.3%, 100%) in adults (5 studies) and 94.5% (88.9%, 97.3%) and 93.8% (85.2%, 97.5%) in children (5 studies). CONCLUSIONS: Anti-tissue transglutaminase sensitivity appears to be sufficient to rule out coeliac disease in children. The high specificity of endomysial antibody in adults supports its use to rule in coeliac disease. This evidence underpins the current development of clinical guidelines for a serological diagnosis of coeliac disease. Studies in primary care are needed to evaluate serological testing strategies in this setting.

Prevalence of neurological problems in a community-based sample of paediatric coeliac disease: a cross-sectional study.

BACKGROUND: The prevalence of and risk factors for neurological problems in childhood coeliac disease (CD) are unclear. METHODS: We performed a cross-sectional, community-based audit of CD in children diagnosed from January 2010 to December 2016 in Lothian. RESULTS: 79 (28%) of 284 children with CD (201, 70.8% female) (mean age 8.3 years, range of 1-16) had neurological problems. Fifteen (5.3%) had headaches/migraine, 10 (3.5%) anxiety, 8 (2.8%) motor/co-ordination problems / ataxia (there were no patients with ataxia), 7 (2.5%) had behavioural issues, 5 (1.8 %) with ASD, 5 (1.8%) low mood, 4 (1.4%) ADD/ ADHD, 3 (1.1%) seizures and 2 (0.7%) had neuropathy. Neurological problems were more common with later age at CD diagnosis (OR 1.07, 95% CI 1.01 to 1.14) and male gender (OR 1.69, 95% CI 0.96 to 2.95). CONCLUSION: Prevalence of neurological problems in children with CD in Lothian is lower than published adult CD studies and similar or lower to the reported prevalence in the general childhood population.

Overview of the Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: Pediatric-specific quality standards for endoscopy are needed to define best practices, while measurement of associated indicators is critical to guide quality improvement. The international Pediatric Endoscopy Quality Improvement Network (PEnQuIN) working group was assembled to develop and define quality standards and indicators for pediatric gastrointestinal endoscopic procedures through a rigorous guideline consensus process. METHODS: The Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument guided PEnQuIN members, recruited from 31 centers of various practice types representing 11 countries, in generating and refining proposed quality standards and indicators. Consensus was sought via an iterative online Delphi process, and finalized at an in-person conference. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: Forty-nine quality standards and 47 indicators reached consensus, encompassing pediatric endoscopy facilities, procedures, endoscopists, and the patient experience. The evidence base for PEnQuIN standards and indicators was largely adult-based and observational, and downgraded for indirectness, imprecision, and study limitations to "very low" quality, resulting in "conditional" recommendations for most standards (45/49). CONCLUSIONS: The PEnQuIN guideline development process establishes international agreement on clinically meaningful metrics that can be used to promote safety and quality in endoscopic care for children. Through PEnQuIN, pediatric endoscopists and endoscopy services now have a framework for auditing, providing feedback, and ultimately, benchmarking performance. Expansion of evidence and prospective validation of PEnQuIN standards and indicators as predictors of clinically relevant outcomes and high-quality pediatric endoscopic care is now a research priority.

Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy Facilities: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: There is increasing international recognition of the impact of variability in endoscopy facilities on procedural quality and outcomes. There is also growing precedent for assessing the quality of endoscopy facilities at regional and national levels by using standardized rating scales to identify opportunities for improvement. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of facilities where endoscopic care is provided to children. Consensus was reached via an iterative online Delphi process and subsequent in-person meeting. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development and Evaluation) approach. RESULTS: The PEnQuIN working group achieved consensus on 27 standards for facilities supporting pediatric endoscopy, as well 10 indicators that can be used to identify high-quality endoscopic care in children. These standards were subcategorized into three subdomains: Quality of Clinical Operations (15 standards, 5 indicators); Patient and Caregiver Experience (9 standards, 5 indicators); and Workforce (3 standards). DISCUSSION: The rigorous PEnQuIN process successfully yielded standards and indicators that can be used to universally guide and measure high-quality facilities for procedures around the world where endoscopy is performed in children. It also underscores the current paucity of evidence for pediatric endoscopic care processes, and the need for research into this clinical area.

Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopic Procedures: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: High-quality pediatric gastrointestinal procedures are performed when clinically indicated and defined by their successful performance by skilled providers in a safe, comfortable, child-oriented, and expeditious manner. The process of pediatric endoscopy begins when a plan to perform the procedure is first made and ends when all appropriate patient follow-up has occurred. Procedure-related standards and indicators developed to date for endoscopy in adults emphasize cancer screening and are thus unsuitable for pediatric medicine. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopic procedures. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: The PEnQuIN working group achieved consensus on 14 standards for pediatric endoscopic procedures, as well as 30 indicators that can be used to identify high-quality procedures. These were subcategorized into three subdomains: Preprocedural (3 standards, 7 indicators), Intraprocedural (8 standards, 18 indicators), and Postprocedural (3 standards, 5 indicators). A minimum target for the key indicator, "rate of adequate bowel preparation," was set at ≥80%. DISCUSSION: It is recommended that all facilities and individual providers performing pediatric endoscopy worldwide initiate and engage with the procedure-related standards and indicators developed by PEnQuIN to identify gaps in quality and drive improvement.

Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopists and Endoscopists in Training: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: High-quality pediatric endoscopy requires reliable performance of procedures by competent individual providers who consistently uphold all standards determined to assure optimal patient outcomes. Establishing consensus expectations for ongoing monitoring and assessment of individual pediatric endoscopists is a method for confirming the highest possible quality of care for such procedures worldwide. We aim to provide guidance to define and measure quality of endoscopic care for children. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopists. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: The PEnQuIN working group achieved consensus on 6 standards that all providers who perform pediatric endoscopy should uphold and 2 standards for pediatric endoscopists in training, with 7 corresponding indicators that can be used to identify high-quality endoscopists. Additionally, these can inform continuous quality improvement at the provider level. Minimum targets for defining high-quality pediatric ileocolonoscopy were set for 2 key indicators: cecal intubation rate (≥90%) and terminal ileal intubation rate (≥85%). DISCUSSION: It is recommended that all individual providers performing or training to perform pediatric endoscopy initiate and engage with these international endoscopist-related standards and indicators developed by PEnQuIN.

Pediatric Endoscopy Quality Improvement Network Pediatric Endoscopy Reporting Elements: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: High-quality procedure reports are a cornerstone of high-quality pediatric endoscopy as they ensure the clear communication of procedural events and outcomes, guide patient care and facilitate continuous quality improvement. The aim of this document is to outline standardized reporting elements that achieved international consensus as requirements for high-quality pediatric endoscopy procedure reports. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used Delphi methodology to identify key elements that should be found in all pediatric endoscopy reports. Item reduction was attained through iterative rounds of anonymized online voting using a 6-point scale. Responses were analyzed after each round and items were excluded from subsequent rounds if ≤50% of panelists rated them as 5 ("agree moderately") or 6 ("agree strongly"). Reporting elements that ≥70% of panelists rated as "agree moderately" or "agree strongly" were considered to have achieved consensus. RESULTS: Twenty-six PEnQuIN group members from 25 centers internationally rated 63 potential reporting elements that were generated from a systematic literature review and the Delphi panelists. The response rates were 100% for all three survey rounds. Thirty reporting elements reached consensus as essential for inclusion within a pediatric endoscopy report. DISCUSSION: It is recommended that the PEnQuIN Reporting Elements for pediatric endoscopy be universally employed across all endoscopists, procedures and facilities as a foundational means of ensuring high-quality endoscopy services, while facilitating quality improvement activities in pediatric endoscopy.

Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement.

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

The rising incidence of celiac disease in Scotland.

BACKGROUND AND OBJECTIVES: Although the incidence of pediatric celiac disease (CD) is increasing globally, it is uncertain whether this is attributed to improved case ascertainment or signifies a true rise. We aimed to identify all incident cases of childhood CD in southeast Scotland over the period 1990 to 2009 to assess trends in total incidence and cases diagnosed as a result of (1) a classic presentation, (2) a nonclassic presentation, or (3) targeted screening. METHODS: Twenty-year retrospective cohort study of case notes, pathology databases, endoscopy, and patient records for all children (<16 years of age) diagnosed with CD on biopsy in southeast Scotland (at-risk population of 225000-233000). Data were age-gender standardized and Poisson regression models used to calculate changes in incidence over time. RESULTS: A total of 266 children were diagnosed from 1990 to 2009 with an increase in incidence from 1.8/100000 (95% confidence interval [CI] 1.1-2.7) to 11.7/100000 (95% CI 9.8-13.9) between the epochs 1990 to 1994 and 2005 to 2009, respectively (P < .0001). The incidence of nonclassic presentation (children with a monosymptomatic presentation and those with extraintestinal symptoms) and actively screened cases increased by 1566% (P < .05) and 1170% (P < .001) from 1990 to 1999 to 2000 to 2009, respectively. However, a rise in the incidence of Oslo classic cases from 1.51/100000 (95% CI 0.91-2.38) in 1990 to 1994 to 5.22/100000 (95% CI 3.98-6.75) in 2005 to 2009 (P < .01) remained evident. CONCLUSIONS: The incidence of pediatric CD increased 6.4-fold over the 20 years. This study demonstrates that this rise is significant for classic CD, indicating a true rise in the incidence of pediatric CD.

Childhood coeliac disease diagnoses in Scotland 2009-2010: the SPSU project.

OBJECTIVES: To establish the incidence of childhood coeliac disease (CD) in Scotland between 1 September 2009 and 31 August 2010, to determine clinical features at presentation and reasons for diagnosis, and to identify any differences in incidence and practice between regions. DESIGN: Prospective data collection through the Scottish Paediatric Surveillance Unit (SPSU). Strategic contacts in each tertiary gastrointestinal region (East, West and North) were emailed monthly to report new cases of CD (<16 years). A clinical questionnaire was completed for each case. Additionally, regional laboratories were asked to report the number of diagnostic antibody tests for CD performed over the year. SETTING: This national study looked at the total cases within Scotland. Scotland has a population of 5.2 million, with the mid-year estimate in 2009 of 912 144 children under the age of 16. RESULTS: 91 new cases were reported, giving an overall adjusted incidence of 10.0/100 000/year. Incidence in the East was 16.3/100 000/year, West 8.1/100 000/year and North 7.7/100 000/year. Cases diagnosed due to active screening in the East (4.6/100 000/year) were more than twice the number observed in the West (2.0/100 000/year) and North (1.3/100 000/year), as was the incidence of classic cases. The most frequent symptoms reported were abdominal pain (50/91; 54.9%), failure to thrive (29/91; 31.9%), fatigue (29/91; 31.9%), diarrhoea (27/91; 29.7%) and bloating (19/91; 20.9%). Twenty-two children (24.2%) were diagnosed due to active screening, of which 14 had associated type 1 diabetes mellitus, one Down syndrome and seven had family history. Fifty-five per cent (12/22) of the patients diagnosed through active screening were asymptomatic. Significantly more CD diagnostic antibody tests were performed per head of population in the East compared with the West (OR 1.65, 95% CI 1.57 to 1.73) and North (OR 1.81, 95% CI 1.70 to 1.92). CONCLUSIONS: Approximately double the incidence of paediatric CD was observed in the East of Scotland. Evidence of more actively screened cases diagnosed and more antibody tests performed in the region suggests a lower threshold to test. An environmental influence cannot be dismissed since more classic cases were also captured. Further research is needed to highlight the role of any exogenous factors.

The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease.

OBJECTIVES: Fecal calprotectin (FC) is elevated in patients with inflammatory bowel disease (IBD). Studies evaluating FC during the initial investigation of children with suspected IBD have been limited, especially with regard to their small patient groups. We aimed to evaluate the diagnostic accuracy of FC in a large regional cohort of children undergoing full upper and lower endoscopy for suspected IBD, comparing FC with six common blood parameters. METHODS: Using a retrospective case-control design all FC measurements carried out between 2005 and 2010 in children <18 years old were obtained. All IBD and non-IBD patients who had a FC measurement available before full endoscopic evaluation for suspected bowel inflammation were examined. FC was measured using the PhiCal Test. Multivariate analyzes and receiver operating characteristic curve generation were used to derive significance. RESULTS: A total of 190 patients (91 IBD and 99 non-IBD controls) met the inclusion criteria. Median FC at diagnosis for the IBD group was 1,265 µg/g (interquartile range (IQR) 734-2,024 µg/g), compared with 65 µg/g (IQR 20-235 µg/g) in controls (P<0.001). FC levels did not vary significantly between patients with Crohn's disease, ulcerative colitis, and IBD unclassified and were not influenced by age or disease location. FC was found to be far superior to commonly utilized blood parameters such as C-reactive protein and white cell count (both P<0.01), with an area under the curve of 0.93 (95% confidence interval 0.89-0.97). CONCLUSIONS: This study demonstrates that FC is an invaluable tool in determining those children who may require endoscopy for suspected IBD, and elevated values should prompt further investigation.

Long-term follow-up of children with 6-thioguanine-related chronic hepatoxicity following treatment for acute lymphoblastic leukaemia.

6-Thioguanine (6-TG) therapy in childhood acute lymphoblastic leukaemia results in chronic hepatotoxicity and portal hypertension. We report follow-up data in a cohort of 10 children with acute lymphoblastic leukaemia and 6-TG-related hepatotoxicity described initially in 2006. Clinically significant portal hypertension was present in the majority of patients several years after cessation of 6-TG treatment. These data reflect the natural history of noncirrhotic portal hypertension and emphasises the need to incorporate ongoing surveillance in the transition arrangement to adult services in this select group of patients.

Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis.

Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a gluten-free diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum samples from 23 acetylcholine receptor antibody positive myasthenia gravis patients with no intestinal symptoms were used to screen for celiac disease. Both endomysial and tissue transglutaminase antibodies were examined. One of 23 (or, about 4.3%) was positive for both IgA-endomysial and IgA tissue transglutaminase antibodies. Endoscopic studies subsequently showed duodenal mucosal scalloping and biopsies confirmed the histopathological changes of celiac disease. Celiac disease and myasthenia gravis may occur together more often than is currently appreciated. The presence of motor weakness in celiac disease may be a clue to occult myasthenia gravis, even in the absence of intestinal symptoms.

Intraoperative upper GI endoscopy ensures an adequate laparoscopic Heller's myotomy.

INTRODUCTION: In this article, we present our case series of laparoscopic Heller's myotomies. These were all performed with the aid of intraoperative upper gastrointestinal (GI) endoscopy. MATERIALS AND METHODS: During a 7-year period, 5 patients underwent a laparoscopic Heller's myotomy. There were 4 male patients and 1 female, with an average age of 12.1 years at operation (range, 9.3-14.9). One 14-year-old boy had had a laparoscopic Heller's procedure performed elsewhere and presented with severe dysphagia while undergoing orthopedic surgery in our hospital. His myotomy had been inadequate, and an intraoperative endoscopy had not been performed. All patients had preoperative upper GI contrast studies performed to confirm the diagnosis of achalasia. Two patients had manometry in addition to the contrast study. One patient had been treated with balloon dilatation preoperatively and another with botox injections. Endoscopy was performed pre- and postmyotomy to ensure adequacy. RESULTS: There were no cases of intraoperative mucosal perforation or conversions to an open procedure. Sixty percent of patients required extension of the myotomy after intraoperative endoscopy. All patients had an uneventful, complication-free postoperative recovery. CONCLUSION: We feel that the addition of endoscopy during laparoscopic Heller's myotomy confers a significant advantage in ensuring that the myotomy is adequate. In our experience, the outcome has been excellent even after previous balloon dilatation or submucosal botox injections.

Seronegative autoimmune hepatitis presenting after diagnosis of coeliac disease: a case report.

The relationship between liver dysfunction and coeliac disease is well established, ranging from transaminitis to chronic liver disease. In this report, we describe for the first time the development of a 'seronegative' autoimmune hepatitis in a teenager previously diagnosed with coeliac disease. He had normal liver function tests (LFTs) at diagnosis and was strictly compliant with a gluten-free diet. On screening blood tests at 1 year post diagnosis, he presented with raised LFTs leading to a diagnosis of autoimmune hepatitis on liver biopsy, successfully treated with mycophenolate mofetil. By using screening LFTs, we may well have prevented this patient from developing disease complications.

Fecal calprotectin complements routine laboratory investigations in diagnosing childhood inflammatory bowel disease.

BACKGROUND: We aimed to study fecal calprotectin in Scottish children with inflammatory bowel disease (IBD) and compare its diagnostic accuracy with blood parameters. METHODS: Stool samples from 48 Scottish children (29 males, 19 females) had calprotectin measured at IBD diagnosis. The median age at diagnosis was 11.2 years (interquartile range [IQR] 8.7-13.0 years). There were 33 patients with Crohn's disease, 5 with ulcerative colitis, and 10 with IBD type unspecified. IBD was diagnosed by standard criteria. Calprotectin was measured using a commercially available kit (PhiCal Test) and 47/48 patients had comparative blood results available at diagnosis. RESULTS: The fecal calprotectin concentrations were raised in 96% (46/48) of patients studied. The median calprotectin value was 750 microg/g (IQR 235.8-1251 microug/g). In comparison with standard blood tests, 32/45 (71.1%) had abnormal erythrocyte sedimentation rate, 19/38 (50.0%) had abnormal C-reactive protein, 29/46 (63.0%) had raised platelets, 12/45 (26.7%) had hypoalbuminemia, and 38/46 (82.6%) had abnormal hemoglobin. We identified 7/47 (14.9%) patients with raised calprotectin at diagnosis who did not have any abnormalities detected in the blood tests performed. All 48 patients (100%) had at least 1 abnormal blood test and/or raised calprotectin at diagnosis. CONCLUSIONS: Calprotectin is significantly more likely to be raised than any commonly employed blood tests at IBD diagnosis. When used in combination with these bloods tests an abnormality was demonstrated in 1 or both tests in all patients at diagnosis in this study. Fecal calprotectin measurement is a significant advance when used contemporaneously and in addition to a routine panel of blood tests in the diagnosis of pediatric IBD.

Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease.

BACKGROUND & AIMS: Childhood-onset inflammatory bowel disease (IBD) might be etiologically different from adult-onset IBD. We analyzed disease phenotypes and progression of childhood-onset disease and compared them with characteristics of adult-onset disease in patients in Scotland. METHODS: Anatomic locations and behaviors were assessed in 416 patients with childhood-onset (276 Crohn's disease [CD], 99 ulcerative colitis [UC], 41 IBD type unclassified [IBDU] diagnosed before seventeenth birthday) and 1297 patients with adult-onset (596 CD, 701 UC) IBD using the Montreal classification. RESULTS: At the time of diagnosis in children, CD involved small bowel and colon (L3) in 51% (138/273), colon (L2) in 36%, and ileum (L1) in 6%; the upper gastrointestinal (GI) tract (L4) was also affected in 51%. In 39%, the anatomic extent increased within 2 years. Behavioral characteristics progressed; 24% of children developed stricturing or penetrating complications within 4 years (vs 9% at diagnosis; P < .0001; odds ratio [OR], 3.32; 95% confidence interval [CI], 1.86-5.92). Compared with adults, childhood-onset disease was characterized by a "panenteric" phenotype (ileocolonic plus upper GI [L3+L4]; 43% vs 3%; P < .0001; OR, 23.36; 95% CI, 13.45-40.59) with less isolated ileal (L1; 2% vs 31%; P < .0001; OR, 0.06; 95% CI, 0.03-0.12) or colonic disease (L2; 15% vs 36%; P < .0001; OR, 0.31; 95% CI, 0.21-0.46). UC was extensive in 82% of the children at diagnosis, versus 48% of adults (P < .0001; OR, 5.08; 95% CI, 2.73-9.45); 46% of the children progressed to develop extensive colitis during follow-up. Forty-six percent of children with CD and 35% with UC required immunomodulatory therapy within 12 months of diagnosis. The median time to first surgery was longer in childhood-onset than adult-onset patients with CD (13.7 vs 7.8 years; P < .001); the reverse was true for UC. CONCLUSIONS: Childhood-onset IBD is characterized by extensive intestinal involvement and rapid early progression.

6-Thioguanine-related chronic hepatotoxicity and variceal haemorrhage in children treated for acute lymphoblastic leukaemia--a dual-centre experience.

BACKGROUND: 6-Thioguanine treatment in childhood acute lymphoblastic leukaemia (ALL) has been shown to cause hepatic veno-occlusive disease, but this usually resolved with drug withdrawal. Recent reports suggested that treatment of ALL with 6-thioguanine can lead to chronic hepatotoxicity and portal hypertension. We describe our experience from 2 UK centres of chronic hepatotoxicity in children receiving maintenance 6-thioguanine for ALL in the national leukaemia protocol ALL 97/99. METHODS: Retrospective review of children who were referred with liver disease secondary to 6-thioguanine treatment of ALL was performed. A paediatric pathologist blinded to the clinical features reviewed liver histology slides. RESULTS: Ten of 75 children (13%) treated with 6-thioguanine in both centres were referred at a median of 6 months (range, 2-29) after discontinuation of chemotherapy. In 8 cases, referral was due to persistent thrombocytopenia and splenomegaly. Two children presented with acute variceal bleeding. All had thrombocytopenia at referral, and ultrasonography showed coarse hepatic echo texture and splenomegaly in all. Endoscopy showed oesophageal varices in 7 and gastric varices in 1. Nine underwent liver biopsy that showed features compatible with nodular regenerative hyperplasia in 5 cases. After a median follow-up of 36 months, a further child has had a variceal haemorrhage and all but 2 children remain thrombocytopenic. CONCLUSIONS: 6-Thioguanine-induced chronic hepatotoxicity is a significant complication in children treated with this agent for ALL. Children may present several months to years after discontinuation of 6-thioguanine. All children given maintenance treatment of ALL with this agent should be screened, and affected children require long-term surveillance.