Survey of the initial management of celiac disease antibody tests by ordering physicians.

BACKGROUND: Appropriate interpretation of a positive celiac antibody test by an ordering physician is important in order to institute proper management. We evaluated why children with an initial positive celiac serology were not referred for diagnostic biopsy or followed with serial testing by the ordering physician. METHODS: Consecutive celiac serologies in all patients less than 18 years of age were evaluated over 3.5 years and 775 children with a positive tissue transglutaminase antibody (TTG) were identified. If no management of a positive TTG could be identified, a survey was sent to the ordering physician. Responses were categorized as appropriate or inappropriate management. RESULTS: Of the 775 patients with a positive TTG, 193 (24.9%, 95% CI 21.9-28.1%) received no follow-up management. We contacted 173 ordering physicians and 120 (69%) responded. Of the 120 responses, 55 patients (45.8%, 95% CI 36.8-55.1%) were managed appropriately and 46 (38.3%, 95% CI 29.7-47.7%) were considered to be inappropriately managed when no repeat TTG was obtained within 18 months. Reasons for inappropriate management included: screen considered to be false positive (44.7%), patient was not experiencing symptoms of celiac disease (31.6%), symptoms had resolved (15.8%), results were not indicative of celiac disease (26.3%) and patients started a gluten-free diet with no evaluation of response (15.8%). In 19 patients the TTG was not acted upon for technical reasons. CONCLUSIONS: Positive TTGs require appropriate interventions. These include: subspecialist referral for further evaluation and/or repeat testing to evaluate: 1) treatment response or 2) patients with minimal or no symptoms.

Management of bone health in patients with celiac disease: Practical guide for clinicians.

OBJECTIVE: To describe clinical issues related to bone health in patients with celiac disease (CD) and to provide guidance on monitoring bone health in these patients. SOURCES OF INFORMATION: A PubMed search was conducted to review literature relevant to CD and bone health, including guidelines published by professional gastroenterological organizations. MAIN MESSAGE: Bone health can be negatively affected in both adults and children with CD owing to the inflammatory process and malabsorption of calcium and vitamin D. Most adults with symptomatic CD at diagnosis have low bone mass. Bone mineral density should be tested at diagnosis and at follow-up, especially in adult patients. Vitamin D levels should be measured at diagnosis and annually until they are normal. In addition to a strict gluten-free diet, supplementation with calcium and vitamin D should be provided and weight-bearing exercises encouraged. CONCLUSION: Bone health can be adversely affected in patients with CD. These patients require adequate calcium and vitamin D supplementation, as well as monitoring of vitamin D levels and bone mineral density with regular follow-up to help prevent osteoporosis and fractures.

Prise en charge de la santé des os chez les patients atteints de la maladie cœliaque: Guide pratique à l'usage des cliniciens.

OBJECTIF: Décrire les enjeux cliniques liés à la santé des os chez les patients atteints de la maladie cœliaque (MC) et orienter la surveillance de la santé des os chez ces patients. SOURCES D'INFORMATION: Une recherche a été effectuée sur PubMed dans le but d'examiner les publications appropriées à la MC et la santé des os, y compris les lignes directrices publiées par des organisations professionnelles de gastro-entérologie. MESSAGE PRINCIPAL: Le processus inflammatoire et la malabsorption du calcium et de la vitamine D compromettent la santé des os chez les adultes et les enfants atteints de la MC. La masse osseuse est réduite chez la plupart des adultes dont la MC est symptomatique au diagnostic. Il faut mesurer la densité minérale osseuse au diagnostic et au suivi, surtout chez les adultes. Il faut mesurer le taux de vitamine D au diagnostic et tous les ans, jusqu'à ce qu'il soit normal. Outre un régime strict sans gluten, il faut assurer la supplémentation en calcium et en vitamine D, et encourager les exercices contre résistance. CONCLUSION: La santé des os peut être compromise chez les patients atteints de la MC. Ces patients ont besoin d'une supplémentation adéquate en calcium et en vitamine D, de même que de la surveillance du taux de vitamine D et de la densité minérale osseuse lors des suivis réguliers afin de prévenir l'ostéoporose et les fractures.

Normalization Time of Celiac Serology in Children on a Gluten-free Diet.

OBJECTIVES: Response to a gluten-free diet (GFD) in children with celiac disease is determined by symptom resolution and normalization of serology. We evaluated the rate of normalization of the transglutaminase (TTG) and antiendomysial (EMA) for children on a GFD after diagnosis. METHODS: Celiac serologies were obtained over 3.5 years after starting a GFD in 228 newly diagnosed children with biopsy-proven celiac disease. Patients were classified into categories based on serology (group A, TTG ≥10 × upper limit of normal [ULN] and EMA ≥ 1:80; group B, TTG ≥10 × ULN and EMA ≤ 1:40; and group C, TTG <10 × ULN) and by severity of histologic injury at diagnosis. RESULTS: In children with the highest serology at diagnosis (group A), 79.7% had an abnormal TTG at 12 months after diagnosis (mean TTG 12 months, 68.8 ±â€Š7.3, normal <20 kU/L). At 2 years, an abnormal TTG persisted in 41.7%. In contrast, only 35% of children with the lowest serology at diagnosis (group C) displayed an abnormal TTG at 12 months (mean TTG 14.3 ±â€Š1.9 kU/L). In those with the most severe mucosal injury, Marsh 3C, 74.2% and 33.2% had an abnormal TTG at 1 and 2 years. CONCLUSIONS: Normalization of celiac serology took >1 year in approximately 75% of GFD-compliant children with the highest celiac serology or most severe mucosal injury at diagnosis. Clinicians must consider serology and histology at diagnosis to properly evaluate response to GFD.

Evidence-Informed Expert Recommendations for the Management of Celiac Disease in Children.

Although the need for effective long-term follow-up for patients with celiac disease (CD) has been recognized by many expert groups, published practice guidelines have not provided a clear approach for the optimal management of these patients. In an attempt to provide a thoughtful and practical approach for managing these patients, a group of experts in pediatric CD performed a critical review of the available literature in 6 categories associated with CD to develop a set of best practices by using evidence-based data and expert opinion. The 6 categories included the following: bone health, hematologic issues, endocrine problems, liver disease, nutritional issues, and testing. Evidence was assessed by using standardized criteria for evaluating the quality of the data, grade of evidence, and strength of conclusions. Over 600 publications were reviewed, and 172 were chosen for inclusion. The thorough review of the results demonstrated that the quality of the data available was often insufficient to provide unequivocal best practices. However, using the available data and the clinical experience of the panel, a practical framework for the management of children with CD was created. These recommendations were developed by our expert panel and do not necessarily reflect the policy of the American Academy of Pediatrics. The potential usefulness of these best practices is underscored by the fact that consensus, measured by the outcome of anonymous voting, was reached by the panel for 24 of the 25 questions. We hope that these best practices may be useful to the pediatric gastroenterology and larger general pediatric communities.

Evaluation of the ESPGHAN Celiac Guidelines in a North American Pediatric Population.

OBJECTIVES: We retrospectively examined the performance of the tissue transglutaminase (TTG), endomysial antibody (EMA) tests, and the ESPGHAN (European Society of Paediatric Gastroenterology, Hepatology and Nutrition) nonbiopsy criteria in a pediatric population. METHODS: Consecutive celiac serologies and corresponding intestinal biopsy results were obtained on children <18 years old over 3.5 years. Patients were classified into three categories: positive TTG, negative TTG, and IgA deficiency. RESULTS: Of the 17,505 patients with celiac serology performed, 775 had a positive TTG, 574 with a negative TTG were biopsied, and 25 were IgA deficient. Of the patients with a TTG ≥10 × upper limit of normal (ULN), positive EMA, and symptoms, 98.2% had biopsies consistent with celiac disease (CD). Four human leukocyte antigen (HLA) DQ2/DQ8-positive patients who met the ESPGHAN nonbiopsy criteria did not have CD. In the group with a TTG 3-10 × ULN, 75.7% EMA-positive patients and only 40% EMA-negative patients had CD (P<0.001). Of those with a TTG 1-3 × ULN, 52.2% EMA-positive patients vs. only 13.3% EMA-negative patients had CD (P<0.01). Of the patients with bulbar and duodenal biopsies, 9.8% had CD confined only in the bulb, especially those with a low titer TTG (P<0.01). CD prevalence in our cohort was 34.6%. Sensitivity, specificity, and positive predictive value of the TTG were 98.7%, 86.4%, and 79.4%, respectively. CONCLUSIONS: The TTG is a very sensitive screen for CD, but positive predictive value improves with a positive EMA titer. To apply the new ESPGHAN guidelines, clinicians must understand the performance of their celiac serology tests.

Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology.

BACKGROUND & AIMS: Guidelines for the management of venous thromboembolism (VTE) from the American College of Chest Physicians do not address patients with inflammatory bowel disease (IBD), a group with a high risk of both VTE and gastrointestinal bleeding. We present recommendations for the prevention and treatment of VTE in patients with IBD. METHODS: A systematic literature search was performed to identify studies on VTE in IBD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Statements were developed through an iterative online platform, then finalized and voted on by a working group of adult and pediatric gastroenterologists and thrombosis specialists. RESULTS: IBD patients have an approximately 3-fold higher risk of VTE compared with individuals without IBD, and disease flares further increase this risk. Anticoagulant thromboprophylaxis is recommended for IBD patients who are hospitalized with IBD flares without active bleeding and is suggested when bleeding is nonsevere. Anticoagulant thromboprophylaxis is suggested during moderate-severe IBD flares in outpatients with a history of VTE provoked by an IBD flare or an unprovoked VTE, but not otherwise. The recommended duration of anticoagulation after a first VTE is based on the presence of provoking factors. Specific suggestions are made for the prevention and treatment of VTE in pediatric and pregnant IBD patients. CONCLUSIONS: Using the American College of Chest Physicians' guidelines as a foundation, we have integrated evidence from IBD studies to develop specific recommendations for the management of VTE in this high-risk population.

Incidence and prevalence of eosinophilic esophagitis in children.

OBJECTIVES: The aim of the present study was to conduct a systematic review with meta-analysis on the epidemiology of eosinophilic esophagitis (EoE) in children. METHODS: Studies investigating incidence and prevalence of EoE in children (≤ 18 years) were identified in a systematic review of MEDLINE (1950-2011) and Embase (1980-2011). Meta-analyses were performed for incidence and subgroups with ≥ 5 studies: esophagogastroduodenoscopy (EGD) for any indication, histologic esophageal disease, and celiac disease, and EGD for abdominal pain. We used a random effects model, Q statistic to assess heterogeneity, and joinpoint analysis to assess time trends. RESULTS: We included 25 studies. The incidence of EoE varied from 0.7 to 10/100,000 per person-year and the prevalence ranged from 0.2 to 43/100,000. The incidence and prevalence increased over time. Prevalence was highest in children with food impaction or dysphagia (63%-88%). The pooled prevalence was 3.7% (95% confidence interval [CI] 2.4-5.1) in EGD for any indication, 24% (95% CI 19-28) in histologic esophageal disease, 2.3% (95% CI 1.0-3.6) in celiac disease, and 2.6% (95% CI 1.2-4.1) in EGD for abdominal pain. CONCLUSIONS: During the last 2 decades, the incidence and prevalence of EoE in children have increased significantly; however, the population-based incidence and prevalence of EoE vary widely across geographic variations, potentially because of variations in case of ascertainment between centers. Because EoE is common among children with food impaction and dysphagia, children with this presenting complaint should be rapidly identified at triage for timely endoscopic assessment.

The changing face of childhood celiac disease in north america: impact of serological testing.

OBJECTIVE: The goal was to evaluate the impact of immunoglobulin A endomysial antibody testing on the incidence and clinical presentation of childhood celiac disease. METHODS: The incidence and clinical presentation of celiac disease in patients <18 years of age in 1990-1996 (pretesting group) versus 2000-2006 (testing group) were compared. RESULTS: The median age at diagnosis was 2 years (95% confidence interval: 2-4 years) in the pretesting group (N = 36), compared with 9 years (95% confidence interval: 8-10 years) in the testing group (N = 199; P < .001); the female/male ratios (1.6:1) were similar (P = .982). The incidence of celiac disease increased from 2.0 cases per 100000 children (pretesting group) to 7.3 cases per 100000 children (testing group; P = .0256). The frequency of classic celiac disease presentations decreased from 67% (pretesting group) to 19% (testing group; P < .001), but the incidence of classic celiac disease did not differ (0.8 vs 1.6 cases per 100000; P = .154). In the testing group, 13 previously unrecognized clinical presentations were observed in 98 children, including 35 with family history, 18 with abdominal pain, and 14 with type 1 diabetes mellitus. The frequency of Marsh IIIc lesions decreased from 64% (pretesting group) to 44% (testing group; P = .0403). In the testing group, classic celiac disease remained predominant (67%) in young children (<3 years), whereas atypical gastrointestinal and silent presentations predominated in older children. CONCLUSIONS: Antibody testing for celiac disease tripled the incidence of celiac disease and quadrupled the median age at diagnosis.

Home blood testing for celiac disease: recommendations for management.

OBJECTIVE: To provide recommendations for the management of patients who inquire about the Health Canada-approved, self-administered home blood tests for celiac disease or who present with positive test results after using the self-testing kit SOURCES OF INFORMATION: PubMed and the Cochrane Database of Systematic Reviews were searched from January 1985 to April 2008, using the subject headings diagnosis of celiac disease and management or treatment of celiac disease. Guidelines for serologic testing and confirmation of diagnosis of celiac disease by the American Gastroenterological Association and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition are used in this review. Level 1 evidence was used. MAIN MESSAGE: Although blood tests are helpful for screening purposes, the confirmatory test for celiac disease is a small intestinal biopsy. CONCLUSION: Patients whose blood tests for celiac disease provide positive results should have endoscopic small intestinal biopsies to confirm the diagnosis before starting a gluten-free diet.

Celiac disease and IgA deficiency: complications of serological testing approaches encountered in the clinic.

BACKGROUND: IgA deficiency causes false-negative IgA-based celiac serology results in patients with celiac disease. Using a case-finding strategy, we examined the prevalence of IgA deficiency, physician evaluation, and management of IgA deficiency during serological testing for celiac disease. METHODS: We reviewed consecutive IgA-endomysial antibody (EMA) and serum IgA results from the laboratory database over 17 months. We cross-referenced seronegative patients with IgA deficiency (IgA <0.06 g/L) to the pathology database to evaluate intestinal biopsy results. Ordering physicians received a questionnaire regarding the management of seronegative patients with IgA deficiency who had no biopsy record. RESULTS: Among the 9533 patients tested for IgA-EMA, 4698 (49%) were tested for IgA deficiency. IgA deficiency occurred in 35 of 4698 (0.75%) patients screened for IgA deficiency. Only 19 of 35 (54%) IgA-deficient patients were diagnosed appropriately with either intestinal biopsy (17 patients) or measurement of IgG-tissue transglutaminase (2 patients). Thirteen (76%) of the 17 IgA-deficient patients who underwent upper endoscopy with or without colonoscopy displayed gastrointestinal pathology on biopsies, including 3 (18%) with celiac disease. No further evaluation to exclude celiac disease was performed for the remaining 16 of 35 (46%) IgA-deficient, EMA-negative patients because of inappropriate management (6 patients), administrative error (7 patients), or patient/physician refusal (3 patients). CONCLUSIONS: IgA deficiency occurred in 1:131 patients tested for celiac disease, and celiac disease occurred in 1:6 of those properly evaluated. Inadequate evaluation of IgA deficiency while testing for celiac disease occurred frequently and resulted in the underdiagnosis of both. Changes in testing algorithms and reporting of results were made to improve testing for celiac disease and IgA deficiency.

Biliary atresia: the Canadian experience.

OBJECTIVE: To determine the outcomes of Canadian children with biliary atresia. STUDY DESIGN: Health records of infants born in Canada between January 1, 1985 and December 31, 1995 (ERA I) and between January 1, 1996 and December 31, 2002 (ERA II) who were diagnosed with biliary atresia at a university center were reviewed. RESULTS: 349 patients were identified. Median patient age at time of the Kasai operation was 55 days. Median age at last follow-up was 70 months. The 4-year patient survival rate was 81% (ERA I = 74%; ERA II = 82%; P = not significant [NS]). Kaplan-Meier survival curves for patients undergoing the Kasai operation at age < or = 30, 31 to 90, and > 90 days showed 49%, 36%, and 23%, respectively, were alive with their native liver at 4 years (P < .0001). This difference continued through 10 years. The 2- and 4-year post-Kasai operation native liver survival rates were 47% and 35% for ERA I and 46% and 39% for ERA II (P = NS). A total of 210 patients (60%) underwent liver transplantation; the 4-year transplantation survival rate was 82% (ERA I = 83%, ERA II = 82%; P = NS). CONCLUSIONS: This is the largest outcome series of North American children with biliary atresia at a time when liver transplantation was available. Results in each era were similar. Late referral remains problematic; policies to ensure timely diagnosis are required. Nevertheless, outcomes in Canada are comparable to those reported elsewhere.

Celiac disease: are endomysial antibody test results being used appropriately?

BACKGROUND: The aim of this study was to retrospectively examine how positive IgA-endomysial antibody (EMA) test results for celiac disease were being interpreted and acted on by physicians in the Calgary Health Region. METHODS: We reviewed consecutive EMA test results, with or without a serum IgA, obtained during a 17-month period. Seropositive tests were cross-referenced to the surgical database to determine the number of patients who underwent intestinal biopsy and the results of the biopsy. We sent questionnaires to the ordering physicians of positive tests with no record of intestinal biopsy. RESULTS: Among 11,716 EMA tests in 9533 patients, 349 results were positive in 313 patients (3%). Intestinal biopsies were performed in 218 (70%) of the seropositive patients; 194 of them were diagnostic of celiac disease. Celiac disease was also found in 10 EMA-negative patients. Of the 109 positive tests performed in 95 patients with no subsequent biopsy, 28 had appropriate indications to not perform a biopsy; the most common reason being that the test had been ordered to follow up on a previous biopsy-proven diagnosis of celiac disease (n = 21). For 33 other positive test results without a subsequent biopsy, management appeared to be inappropriate, most commonly (n = 21) because of a recommendation to follow a gluten-free diet despite lack of a tissue diagnosis of celiac disease. For the remaining 48 positive EMA results, administrative issues prevented evaluation (n = 19), the patients refused further evaluation (n = 11), or physician surveys were not returned (n = 18). CONCLUSIONS: Celiac disease affected 2% of patients, with a similar prevalence in male and female patients. Most positive EMA tests (77%) were appropriately managed by physicians. Beginning a gluten-free diet without biopsy or failing to follow up on a positive EMA test remain common errors of management.

The Canadian Celiac Health Survey.

The purpose of this study was to characterize the diagnostic process, frequency of associated disorders, family history, and impact of a gluten-free diet in individuals with celiac disease. All members of the Canadian Celiac Association (n=5240) were surveyed with a questionnaire. Respondents included 2681 adults with biopsy-proven celiac disease. The mean age was 56 years. Most common presenting symptoms included abdominal pain (83%), diarrhea (76%), and weight loss (69%). The mean delay in diagnosis was 11.7 years. Diagnoses made prior to celiac disease included anemia (40%), stress (31%), and irritable bowel syndrome (29%). Osteoporosis was common. Prior to diagnosis, 27% of respondents consulted three or more doctors about their symptoms. Delays in diagnosis of celiac disease remain a problem. Associated medical conditions occur frequently. More accurate food labeling is needed. Improved awareness of celiac disease and greater use of serological screening tests may result in earlier diagnosis and reduced risk of associated conditions.

Celiac disease: evaluation of the diagnosis and dietary compliance in Canadian children.

OBJECTIVES: We sought to characterize the clinical features at presentation as well as the associated disorders, family history, and evaluation of compliance with a gluten-free diet in children with celiac disease from across Canada. STUDY DESIGN: All members (n = 5240) of the Canadian Celiac Association were surveyed with a questionnaire. Of the 2849 respondents with biopsy-confirmed celiac disease, 168 who were < 16 years old provided the data reported here. RESULTS: The mean age when surveyed was 9.1 +/- 4.1 years, and 58% were female. Median age at diagnosis was 3.0 years with a range of 1 to 15 years. Presenting symptoms included abdominal pain (90%), weight loss (71%), diarrhea (65%), weakness (64%), nausea/vomiting (53%), anemia (40%), mood swings (37%), and constipation (30%). Almost one third of families consulted > or = 2 pediatricians before confirmation of the diagnosis. Before the recognition of celiac disease, other diagnoses received by these children included anemia (15%), irritable bowel syndrome (11%), gastroesophageal reflux (8%), stress (8%), and peptic ulcer disease (4%). A serological test was performed to screen for celiac disease in 70% of those in this population. Eight percent had either type 1 diabetes mellitus or a first-degree relative with celiac disease. Almost all respondents (95%) reported strict adherence to a gluten-free diet, and 89% noted improved health. Reactions after accidental gluten ingestion developed in 54% of the children between 0.5 and 60 hours after ingestion with a median of 2.0 hours. Reactions included abdominal discomfort (87%), diarrhea (64%), bloating (57%), fatigue (37%), headache (24%), and constipation (8%), and most displayed > 1 symptom. Although most adjusted well to their disease and diet, 10% to 20% reported major disruptions in lifestyle. Twenty-three percent felt angry all or most of the time about following a gluten-free diet. Only 15% avoided traveling all or most of the time, and during travel, 83% brought gluten-free food with them all of the time. More than half of the families avoided restaurants all or most of the time. Twenty-eight percent of the respondents found it extremely difficult to locate stores with gluten-free foods, and 27% reported extreme difficulty in finding gluten-free foods or determining if foods were free of gluten. Sixty-three percent of the respondents felt that the information supplied by the Canadian Celiac Association was excellent. Gastroenterologists provided excellent information to 44%, dietitians to 36%, and the family physician to 11.5%. When asked to select 2 items that would improve their quality of life, better labeling of gluten-containing ingredients was selected by 63%, more gluten-free foods in the supermarket by 49%, gluten-free choices on restaurant menus by 49%, earlier diagnosis of celiac disease by 34%, and better dietary counseling by 7%. CONCLUSIONS: In Canada, children with celiac disease present at all ages with a variety of symptoms and associated conditions. Delays in diagnosis are common. Most children are compliant with a gluten-free diet. A minority of these children experience difficulties in modifying their lifestyles, and gluten-free foods remain difficult to obtain.

A pilot study of the use of epidermal growth factor in pediatric short bowel syndrome.

BACKGROUND: This study examined the effects of enterally administered epidermal growth factor (EGF) on nutrient absorption and tolerance of enteral feeds in pediatric patients with short bowel syndrome (SBS). METHODS: Patients identified with severe SBS (<25% bowel length predicted for age) were prospectively enrolled in treatment using human recombinant EGF (1-53); 100 microg/kg per day given mixed with enteral feeds and patients were treated for 6 weeks. End points followed were patient weight, tolerance of enteral feeds, nutrient absorption, and intestinal permeability as determined using carbohydrate probes and hematologic values for liver function parameters. RESULTS: Five patients were treated with EGF; all showed a significant improvement in carbohydrate absorption (3-0 methylglucose): absorption 24.7% +/- 9.7% pretreatment vs 34.1% +/- 13.8% posttreatment and improved tolerance of enteral feeds (enteral energy as % of total energy, 25% +/- 28% pretreatment vs 36% +/- 24% posttreatment; mean +/- SD; P < .05 by Wilcoxon's signed rank test). Epidermal growth factor treatment was not associated with significant changes in intestinal permeability, the rate of weight gain, or liver function tests. During the treatment phase, no patients developed episodes of sepsis; however, within 2 weeks of discontinuation of EGF treatment, 3 patients developed septic episodes. No adverse effects of EGF administration were noted. CONCLUSIONS: These results suggest that enteral treatment with EGF in pediatric SBS improves nutrient absorption, increases tolerance with enteral feeds, and may improve the infection rate. Further studies exploring treatment strategies including the timing and duration of EGF administration are indicated.

Crohn's disease and cheilitis.

A five-year-old boy presented to his family physician with painless swelling of both lips. One year later he developed abdominal pain, nonbloody diarrhea, weight loss and joint pains. Colonoscopic examination demonstrated patchy erythema, friability and multiple aph-thous ulcers consistent with the appearance of Crohn's colitis, and treatment with prednisone was initiated. Colonic biopsies displayed a chronic inflammatory cell infiltrate, focal cryptitis and fissure formation. The patient's lip swelling relapsed on multiple occasions when steroids were tapered, despite minimal intestinal symptoms of Crohn's disease. The objective of the present report is to alert physicians to this unusual presentation of Crohn's disease and that cheilitis may run a protracted course.

Arginine supplementation prevents necrotizing enterocolitis in the premature infant.

OBJECTIVES: To determine whether supplementation with L -arginine reduces the incidence of all stages of necrotizing enterocolitis (NEC) in premature infants with birth weight < or =1250 g and gestational age < or =32 weeks. STUDY DESIGN: In a randomized, double-blind, placebo-controlled study, 152 premature infants were prospectively, randomly assigned to receive either supplemental L -arginine (1.5 mmol/kg per day; n =75 [group A]) or placebo (control group; n = 77 [group B]) with oral feeds/parenteral nutrition during the first 28 days of life. Nutrient intake, plasma ammonia, arginine, and amino acid concentrations were measured in all infants at days 3, 14, and 28 and at the time of diagnosis of NEC. RESULTS: NEC developed in 5 infants in group A compared with 21 infants in group B (P <.001). Arginine intake and plasma arginine concentrations were similar in both groups at study entry and (as expected) increased in group A at days 14 and 28. Plasma arginine concentrations were lower in both groups at time of diagnosis of NEC. No significant differences in maternal and neonatal demographics, nutrient intake, plasma ammonia and total and essential amino acid concentrations were present between the two groups. CONCLUSIONS: Arginine supplementation (1.5 mmol/kg per day) in premature infants reduces the incidence of all stages of NEC.