J. Decker Butzner

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 ≥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.

Plasma L-arginine concentrations in premature infants with necrotizing enterocolitis

OBJECTIVE To determine whether L-arginine concentrations (the substrate for nitric oxide synthesis) are lower in premature infants in whom necrotizing enterocolitis (NEC) develops than in unaffected infants. METHODS We measured arginine and nutritional intake, plasma arginine, glutamine, total amino acids, and ammonia concentrations in 53 premature infants (mean gestational age +/- SD: 27 +/- 1.7 weeks) at risk of NEC. Measurements were done on days 3, 7, 14 and 21 and just before treatment in infants with NEC. RESULTS Necrotizing enterocolitis developed in 11 infants between postnatal days 1 and 26. On day 3, plasma arginine concentrations were decreased compared with normal published values (mean +/- SE, 41 mumol/L +/- 4). Arginine concentrations increased with day of life of measurement (p < 0.001) and arginine intake (p < 0.001). Plasma arginine concentrations were significantly lower at the time of diagnosis in infants with NEC compared with control subjects, even after adjusting for arginine intake and day of life (p = 0.032). Plasma glutamine and total amino acid concentrations were not significantly different in infants with NEC compared with control subjects. Plasma ammonia concentrations were elevated on day 3 (mean +/- SE, 72 +/- 3.3 mumol/L) and decreased with postnatal age (p < 0.001) and increasing plasma arginine concentrations (p < 0.001). CONCLUSION Plasma arginine concentrations are decreased at the time of diagnosis in premature infants with NEC. The potential benefit of arginine supplementation in the prevention of the disease deserves evaluation.

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 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.

Oral rehydration solution in the year 2000: pathophysiology, efficacy and effectiveness.

The use of oral rehydration solution (ORS) with early refeeding forms the basis of therapy for dehydration secondary to diarrhoea ORS has produced such positive results in dehydrated patients that no further scientific demonstration is needed to confirm its efficacy. This review presents several issues that remain unsettled or controversial. They include the following. 1. The mechanism of water handling by the intestine is discussed; this is more complex than initially thought, at the epithelial, cellular and molecular level. 2. The composition of ORS which has been successfully adapted for the most frequent conditions, except for severely malnourished children, is described. 3. In contrast to the strong scientific basis and obvious efficacy in rehydration of ORS, its consequences for growth, nutrition and mortality are difficult to demonstrate, unless adequate long-term nutritional support is also provided in addition to ORS. 4. Finally, discrepancies between the recommendations and the practice of oral rehydration therapy are now well documented. Analysis of the causes of these discrepancies may participate in improving public health campaigns.

Inhibition of short-chain fatty acid absorption and Na+ absorption during acute colitis in the rabbit

BACKGROUND/AIMS Short-chain fatty acids (SCFAs) provide energy for colonocytes and stimulate colonic fluid and electrolyte absorption. The impact of acute colitis on SCFA-stimulated Na+ absorption and SCFA absorption was examined. METHODS Proximal colon from rabbits infected with Yersinia entercolitica, a pair-fed group, and controls was mounted in Ussing chambers, and Na+ transport, short-circuit current, and tissue conductance were examined during a basal period and after stimulation with the SCFAs, butyrate, or propionate. Propionate transport and luminal SCFA concentration were evaluated. RESULTS Butyrate and propionate stimulated electroneutral Na+ absorption above basal levels in the control and pair-fed groups, as evidenced by significant increases in mucosal-to-serosal and net Na+ fluxes with no change in serosal-to-mucosal flux, short-circuit current, or conductance. Butyrate-stimulated Na+ absorption and propionate absorption were blocked by amiloride, an inhibitor of Na(+)-H+ exchange. In the infected group, both butyrate and propionate failed to stimulate colonic Na+ absorption above basal levels. Propionate absorption was inhibited, and epinephrine failed to stimulate Na+ or propionate absorption. Luminal SCFA concentrations were increased in acute colitis. CONCLUSIONS Inhibition of SCFA-stimulated Na(+)-H+ exchange and SCFA absorption contribute to the diarrheal fluid loses observed in acute colitis and may reduce colonocyte energy supply.

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.

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 ± 7.3, 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 ± 1.9 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.

Crohn-like enteritis presenting as hypoglycemia in a patient with glycogen storage disease type 1b, treated with granulocyte colony-stimulating factor and splenectomy.

Glycogen storage disease type 1b (GSD 1b) results from a defect in the microsomal membrane translocase system for glucose-6-phosphate. Glycogen storage disease type 1a (GSD 1a) differs from GSD 1b in that it results from a defect in the enzyme glucose-6phosphatase (1,2). This defect associated with GSD 1b inhibits the hydrolysis of glucose-6-phosphate by the microsome for transport into the lumen of the endoplasmic reticulum of hepatocytes (1). Features associated with GSD 1b, as in GSD 1a, include hypoglycemia, hepatomegaly, growth failure, lactic acidosis, hyperuricemia, and hyperlipidemia. Recurrent infection secondary to neutropenia and neutrophil dysfunction is a distinctive feature of GSD type 1b (3). Impaired neutrophil chemotaxis, mobilization, decreased superoxide production, and maturational arrest at various stages of myeloid development all contribute to the abnormal neutrophil function observed in this condition (3–5). Other associations include Crohn-like enteritis (6,7), oral and anal ulcerations (4), esophagitis (7), and iron deficiency anemia (5). Neutropenia and neutrophil dysfunction are probable causes of Crohn-like enteritis in GSD 1b. Crohn-like enteritis also has been reported in patients with neutropenia and other diseases characterized by neutrophil dysfunction, such as chronic granulomatous disease (8,9). Treatment with granulocyte colony-stimulating factor (G-CSF) improves neutropenia, neutrophil function, and Crohn-like enteritis in patients with GSD 1b (5,10,11). The purpose of this report is to increase awareness that hypoglycemia may be a sign of Crohn-like enteritis in patients with GSD 1b who have responded previously to G-CSF. Furthermore, as a consequence of G-CSF therapy, splenomegaly developed in the patient described in this case report. Splenectomy was performed to treat this side effect. CASE REPORT

PLASMA ARGININE LEVELS DECREASE WITH INCREASING SEVERITY OF RESPIRATORY DISTRESS SYNDROME (RDS) IN PREMATURE BABIES. 1516

PLASMA ARGININE LEVELS DECREASE WITH INCREASING SEVERITY OF RESPIRATORY DISTRESS SYNDROME (RDS) IN PREMATURE BABIES. 1516