Pornthep Tanpowpong

Predictors of Gluten Avoidance and Implementation of a Gluten-Free Diet in Children and Adolescents without Confirmed Celiac Disease

OBJECTIVES To determine independent predictors of gluten avoidance and of a physicians decision to initiate a gluten-free diet (GFD) in children and adolescents without confirmed celiac disease. STUDY DESIGN We performed a structured medical record review of 579 patients aged 1-19 years presenting for evaluation of celiac disease between January 2000 and December 2010 at a large Boston teaching hospital. We collected data including demographic information, medical history, serology, small intestinal biopsy, history of gluten avoidance, and the postworkup recommendation of implementation of a GFD. Predictors of gluten-related issues were identified by multivariate logistic regression. RESULTS Among 579 children without a previous diagnosis of celiac disease (mean age, 8.7 years), 43 (7.4%) had ever avoided gluten. Independent predictors of gluten avoidance were irritability or poor temper (OR, 3.2), diarrhea (OR, 2.5), weight issues (OR, 0.4), pervasive developmental disorder (OR, 5.3), and family history of celiac disease (OR, 2.2). Among 143 children without confirmed celiac disease who underwent diagnostic evaluation, several predictive factors were associated with a physician- recommended/parent-initiated GFD: irritability (OR, 6.4), diarrhea (OR, 3.4), pervasive developmental disorder (OR, 7.9), and positive serology before the referral (OR, 4.3). CONCLUSION Gluten avoidance among children and adolescents without a previous diagnosis of celiac disease is relatively common. The identified predictors suggest that gluten avoidance is associated with nonspecific behavioral and gastrointestinal complaints and perhaps with the perceived dietary responses in another family member thought to have celiac disease.

Age-related patterns in clinical presentations and gluten-related issues among children and adolescents with celiac disease.

OBJECTIVES:Celiac disease (CD) is common and often cited as an “iceberg” phenomenon (i.e., an assumed large number of undiagnosed cases). Recently, atypical or asymptomatic manifestations are becoming more commonly described in older children and adolescents. Moreover, CD diagnosis in children can be complicated by several factors, including its diverse clinical presentations, delay in recognizing CD signs and symptoms, and premature dietary gluten avoidance before the formal diagnosis of CD. To date, few studies have directly examined age-related differences in clinical characteristics and gluten-related issues among children with CD. The aim of this study was to determine age-related patterns in clinical characteristics and gluten-related issues among children with confirmed CD.METHODS:We performed a structured medical record review of biopsy-proven CD patients, aged 0–19 years, between 2000 and 2010 at a large Boston teaching hospital. Data collection included demographics, medical history, gluten-related issues, and diagnostic investigations (CD-specific serology, upper gastrointestinal endoscopy, and small intestinal biopsy). The first positive duodenal biopsy with Marsh III classification defined age of diagnosis. Patients were divided into three age groups for comparisons of the aforementioned characteristics: infant-preschool group (0–5 years), school-aged group (6–11 years), and adolescence group (12–19 years).RESULTS:Among 411 children with biopsy-proven CD, the mean age was 9.5 (s.d. 5.1) years. Most were female (63%) and white (96%). All children had positive CD-specific serology. Most children presented with either abdominal complaints or bowel movement changes. Overall, boys were more common among infant-preschool group compared with the other age groups. More distinct clinical manifestations (vomiting, bowel movement changes, and weight issues) were apparent in the youngest group, whereas school-aged children had more subjective abdominal complaints at the initial presentation. Conversely, the adolescents were most likely to present without any gastrointestinal (GI) symptoms, but not when this was combined with absence of weight issues. Age of diagnosis was not associated with atypical extraintestinal CD presentations. Regarding the gluten-related issues, 10% of school-aged children avoided dietary gluten before the formal CD diagnosis, and 27% of the adolescents reported dietary gluten transgression within the first 12 months of diagnosis, significantly higher than the other age groups. Age differences in histopathology were also found. Whereas the infant-preschool group had a higher proportion of total villous atrophy, the older children were more likely to have gross duodenal abnormalities and chronic duodenitis suggestive of CD at the time of diagnosis.CONCLUSIONS:Children and adolescents with CD have age-related patterns in both the clinical presentations and gluten-related issues. More pronounced clinical and histological features were determined in younger children, whereas older children more commonly presented with solely subjective abdominal complaints or even without any GI symptoms. However, silent and atypical extraintestinal CD presentations were comparable between age groups. In addition to the aforementioned presentations, the higher rates of dietary gluten avoidance and transgression in older children make CD diagnosis and management particularly challenging. These age-related patterns may further increase awareness, facilitate early diagnosis, and improve patient care of pediatric CD.

Early-life vitamin D deficiency and childhood-onset coeliac disease

Many studies have investigated the aetiological roles of genetic and environmental factors in coeliac disease (CD) with the long-term goal of developing an effective primary prevention strategy. CD is a condition with dysregulated systemic and intestinal mucosal immune responses to dietary gluten proteins among genetically predisposed individuals. We recently described spring birth as a novel risk factor for CD in children. We believe that the association between season of birth and CD is due to seasonal differences in sunlight exposure and subsequent vitamin D status. Concomitant with global increases in CD prevalence, vitamin D deficiency also is increasingly recognized in children worldwide. Recent studies have shown that vitamin D deficiency can cause improper immune responses, abnormal intestinal mucosal integrity and impaired local defence to pathogenic microbial agents. In conjunction with other potential aetiological factors, we propose a hypothesis model of early-life vitamin D deficiency in the pathogenesis of childhood-onset CD.

Predictors of duodenal bulb biopsy performance in the evaluation of coeliac disease in children.

Aims Studies on the role of duodenal bulb biopsy (DBB) in coeliac disease (CD) evaluation have increased in recent years; growing evidence suggests that the disease can present solely in the duodenal bulb. Moreover, recent CD guidelines recommend obtaining a DBB. The study aim was to examine DBB performance in children undergoing CD evaluation and to identify independent predictors of DBB performance. Methods The authors performed a structured chart review of children aged <18 years who underwent CD evaluation between 2000 and 2010 at a large teaching hospital. The authors collected data including demographics, serology, endoscopy and histopathological findings. Predictors of DBB performance (obtained vs not obtained) were determined using multivariable logistic regression. Results Among 616 children who underwent endoscopy, DBB was performed in 103 children (17%, 95% CI 14% to 20%) with an increasing trend in the more recent years (2008–2010, 25%; 2004–2007, 16%; and 2000–2003, 5%, p<0.001). Three independent predictors of DBB performance were older age at endoscopy (OR 1.05 per year of age), gross gastric antral abnormalities (OR 2.81) and gross duodenal abnormalities (OR 5.55). Regarding the DBB histological findings, patchiness of CD was found in 15%. Positive Marsh III biopsy presented solely on the DBB in 6/103 (6%, 95% CI 2% to 12%) children. Conclusions The authors found a significant increase in DBB performance over time, but the overall performance remains suboptimal. Improving education on obtaining a DBB for CD evaluation is crucial, especially among those children in whom DBB is more likely to be omitted.

Characteristics of children with positive coeliac serology and normal villous morphology: potential coeliac disease

Positive coeliac serology with normal villous morphology (NVM) indicates potential coeliac disease (CD). Few studies have compared characteristics of NVM vs villous atrophy in patients with positive serology. Our aim was to determine the independent clinical predictors of NVM in children with positive CD serology. We performed a structured medical record review of patients aged 1–19 years who presented for an initial CD evaluation between 2000 and 2010 at a large teaching hospital. Data collection included demographics, medical history, prior history of gluten avoidance, CD‐specific serology, oesophagogastroduodenoscopy and histopathology. Predictors of NVM (vs Marsh III) were determined using multivariable logistic regression. Among 320 patients with positive serology, we identified 62 patients (19%, 95% CI 15–24) with NVM (i.e. potential CD). Younger children may have been more likely to exhibit NVM (p = 0.06). Three significant predictors of NVM were prior gluten avoidance (OR 4.17, 95% CI 1.02–17.13), positive tissue transglutaminase antibody but <100 U/mL (OR 14.75, 95% CI 3.33–65.30), and absence of gross duodenal abnormalities (OR 3.48, 95% CI 1.51–8.03). Among children with positive CD serology, prior gluten avoidance predicts NVM. Future studies are warranted on the impact of gluten intake and CD testing in children without prior established CD diagnosis.

Predictors of dietary gluten avoidance in adults without a prior diagnosis of celiac disease

OBJECTIVE Prior studies have shown that dietary gluten avoidance (DGA) is relatively common in children without previously diagnosed celiac disease (CD), and several clinical predictors of DGA have been found. However, available data on predictors of DGA in adults without diagnosed CD are limited. The aim of this study was to determine the independent predictors of DGA in this population. METHODS We performed a structured medical record review of 376 patients, ages ≥ 20 y, who had never been formally diagnosed with CD, presenting for an initial CD evaluation (ICD-9-CM 579.0) between January 2000 and December 2010 at two large Boston teaching hospitals. We collected data including demographic characteristics, medical history, history of CD serology before referral, and self-reported DGA. Predictors of DGA were determined using multivariable logistic regression. RESULTS Mean age was 47 (SD = 17) years. We found that 41 patients (10.9%; 95% confidence interval [CI], 7.9-14.5) had avoided gluten at some time in their lives. Most patients had subjective abdominal complaints or bowel movement changes. History of CD seropositivity before referral was noted in 14%. Independent predictors of DGA (P < 0.05) were lactose intolerance (odds ratio [OR], 2.8; 95% CI, 1.1-7.5), food allergy (OR, 3.8; 95% CI, 1.04-13.7), and history of positive serology of less-specific CD markers before the referral (OR, 3.2; 95% CI, 1.3-7.9). CONCLUSIONS Gluten avoidance is common in a clinic population of adults without prior CD diagnosis. The recognized predictors suggest that DGA may associate with conditions presenting with nonspecific gastrointestinal complaints and perhaps with the perceived benefits of DGA among patients with prior history of positive CD serology.

First pediatric case of Chromobacterium haemolyticum causing proctocolitis.

Bloody diarrhea in children is usually due to either infectious or inflammatory etiology, but infection is far more common than inflammatory bowel disease in children worldwide. If, however, the patient has unfavorable response to antibiotics and a definite infectious agent has yet to be identified; colonoscopy should be performed. The current patient presented with acute onset of mucous bloody diarrhea. Stool culture was initially identified as Vibrio mimicus and later identified as Aeromonas schubertii but the biochemistry did not fit well with either organism. After a prolonged course of hematochezia despite i.v. antibiotics, colonoscopy was performed that showed inflammation in the rectosigmoid area. Meanwhile, the final biochemistry tests and 16s rRNA sequencing of the organism confirmed Chromobacterium haemolyticum infection. Twelve weeks after the initial colonoscopy, repeat colonoscopy showed post‐infectious colitis. Herein we report on the first pediatric case of C. haemolyticum infection causing proctocolitis.

Use of the i2b2 research query tool to conduct a matched case–control clinical research study: advantages, disadvantages and methodological considerations

BackgroundA major aim of the i2b2 (informatics for integrating biology and the bedside) clinical data informatics framework aims to create an efficient structure within which patients can be identified for clinical and translational research projects.Our objective was to describe the respective roles of the i2b2 research query tool and the electronic medical record (EMR) in conducting a case-controlled clinical study at our institution.MethodsWe analyzed the process of using i2b2 and the EMR together to generate a complete research database for a case–control study that sought to examine risk factors for kidney stones among gastrostomy tube (G-tube) fed children.ResultsOur final case cohort consisted of 41/177 (23%) of potential cases initially identified by i2b2, who were matched with 80/486 (17%) of potential controls. Cases were 10 times more likely to be excluded for inaccurate coding regarding stones vs. inaccurate coding regarding G-tubes. A majority (67%) of cases were excluded due to not meeting clinical inclusion criteria, whereas a majority of control exclusions (72%) occurred due to inadequate clinical data necessary for study completion. Full dataset assembly required complementary information from i2b2 and the EMR.Conclusionsi2b2 was critical as a query analysis tool for patient identification in our case–control study. Patient identification via procedural coding appeared more accurate compared with diagnosis coding. Completion of our investigation required iterative interplay of i2b2 and the EMR to assemble the study cohort.

A rare cause of multiple small bowel ulcers and strictures in a 10-year-old child

Enteritis and small bowel ulcers can be caused by inflammatory bowel disease, drug-induced enteritis, cytomegalovirus, tuberculosis, or intestinal lymphoma. Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is an uncommon idiopathic cause of ulceration and stricture of the small bowel. CMUSE can occur in adults, but only few pediatric cases have been reported. Inflammatory bowel disease and other causes should be carefully sought first before the diagnosis of CMUSE can be made. Previous reports demonstrated that surgical intervention may be necessary for both diagnostic and therapeutic purposes. With regard to the management, systemic corticosteroids may help, and surgery plays a role in patients present with signs of intestinal obstruction. We report a young girl who presented with a prolonged history of refractory iron deficiency anemia with protein-losing enteropathy without other obvious gastrointestinal symptoms. She underwent several laboratory and endoscopic investigations as well as histopathology of the resected full-thickness small bowel area before a proposed diagnosis of CMUSE was made. A trial of immunosuppression (both prednisolone and azathioprine) was initiated that provided a relatively satisfactory result.

Short article: Stool cytomegalovirus polymerase chain reaction for the diagnosis of cytomegalovirus-related gastrointestinal disease

Objectives The diagnosis of cytomegalovirus-related gastrointestinal disease (CMV-GI disease) still requires histopathology, but biopsy is considered invasive. Stool CMV PCR has been reported in adults as an alternative method to diagnose this condition; hence, the results between studies are discrepant. Moreover, no pediatric studies on stool CMV real-time PCR in CMV-GI disease have been carried out. Here, we evaluate the value of stool CMV real-time PCR in detecting CMV-GI disease among immunocompromised children. Methods We enrolled immunocompromised patients aged younger than 20 years who presented with gastrointestinal symptoms at a teaching hospital during January 2015–March 2016. Stool samples were analyzed for CMV real-time PCR. All patients underwent esophagogastroduodenoscopy and colonoscopy with mucosal biopsy. Results We performed stool CMV real-time PCR in 31 patients, but two could not undergo endoscopy. Therefore, 29 patients were analyzed. Two additional stool samples showed inhibitors that interfere with the PCR testing and were precluded from the final analysis. Among 27 patients, we found CMV-GI disease in seven (26%) patients. The sensitivity, specificity, and accuracy of stool CMV real-time PCR were 71, 85, and 82%, respectively. We also found that all patients with CMV-GI disease had positive plasma CMV real-time PCR (>150 copies/ml). A significant association between stool and plasma CMV real-time PCR was also noted (P<0.001). Conclusion Stool CMV real-time PCR may be used as a noninvasive tool in the diagnosis of CMV-GI disease. Plasma CMV real-time PCR shows a significant correlation with stool CMV real-time PCR and also represents high diagnostic values.