Time to recognize atypical celiac disease in Indian children.

BACKGROUND/OBJECTIVE: There is scant information about atypical (non-diarrheal) presentation of celiac disease (CD) from India. We conducted this study to compare non-diarrheal and diarrheal presentations of CD in children. METHODS: From November 2003 to December 2005, we prospectively screened two groups of children for CD, group I with diarrhea and group II without diarrhea but with atypical presentations (unexplained growth retardation, refractory anemia, refractory rickets, chronic constipation and abdominal distension). Screening was done with IgA antiendomysial antibody (EMA) followed by duodenal biopsy if EMA was positive. Celiac disease was diagnosed according to modified ESPGHAN criteria. RESULTS: A total of 200 children were screened (103 in group I and 97 in group II) and CD was diagnosed in 42 (classical 24, atypical 18). Presentation of atypical CD were; short stature 6, anemia 4, abdominal distension 3, rickets 2, and constipation, diabetes mellitus, delayed puberty in 1 case each. Patients with atypical CD were older (median age 10.4 years vs 5.5 years, p< 0.007) than classical cases. On mean (SD) follow-up of 12.6 (7.5) months all showed response to gluten-free-diet, and median gain in weight, height and final hemoglobin levels were similar in the two groups. CONCLUSION: Atypical CD is not uncommon in India. Children with atypical CD present at an older age. Likelihood of finding CD is high in children with anemia, short stature and rickets.     

Prevalence of celiac disease in Indian children with type 1 diabetes

Background

Type 1 diabetes (T1D) patients are at an increased risk of having celiac disease (CD). We evaluated the prevalence and clinical profile of CD in children and adolescents with T1D and reviewed the Indian literature to determine prevalence and reasons for variability.

Methods

In this cross-sectional study, subjects with T1D were prospectively evaluated with a demographic and gastrointestinal (GI) questionnaire, human IgA-tissue transglutaminase (IgA-tTGA), and endoscopic duodenal biopsy in serology positive patients. Studies evaluating prevalence of CD in T1D from India were reviewed.

Results

Fourteen (13.6 %) of the 103 (52 boys, 13 years [2–20]) T1D patients were IgA-tTGA (182 U [47–300]) positive and 3.8 % (4/103) had villous atrophy on histology. Subjects with T1D and CD (n = 4) were younger at onset of T1D (32.5 ± 12.6 vs. 110.5 ± 53.8 months; p < 0.005) and more often had GI symptoms (pain abdomen [2/4 vs. 6/89; p = 0.01], stool frequency of 2–3/day [3/4 vs. 38/89; p = 0.004]) than screen negative T1D (n = 89). Growth and glycemic control were not different between the groups. In the 7 Indian studies involving 915 children and adults, 13.8 % (8 % to 17.8 %) T1D were serology positive. Prevalence of CD was reported as 6.9 % (2.3 % to 11.1 %), but only 3.1 % (2.3 % to 4.2 %) had villous atrophy on histology.

Conclusions

Potential CD and CD were present in 13.6 % and 3.8 % children with T1D respectively. T1D with CD have onset of diabetes at younger age and were more often symptomatic than screen negative T1D.

     

Cirrhosis in children with celiac disease

BACKGROUND: Liver involvement represents an extra-intestinal feature of celiac disease (CD) and shows a clinical spectrum varying from nonspecific reactive hepatitis to cirrhosis. Here we report the association of cirrhosis with CD in 5 children. PATIENTS AND METHODS: The mean age of the patients was 9.4 +/- 2.8 years. Viral, metabolic, and autoimmune etiology of liver disease was ruled out. Intestinal and liver biopsies were performed to confirm the histologic diagnosis in all subjects. RESULTS: Three of the patients had chronic diarrhea and hepatosplenomegaly in whom diagnoses of CD and cirrhosis were established at presentation simultaneously. In the other 2 patients, CD was diagnosed following an initial diagnosis of cirrhosis. At diagnosis, alanine aminotransferase (range, 64-271 IU/L) and aspartate aminotransferase (range, 90-225 IU/L) values were elevated. After 1 to 5 years of a gluten-free diet (GFD), normalization of serum aminotransferase levels and clinical improvement were observed in 3 patients with strict GFD. The other 2 patients without improvement of the liver disease had poor dietary compliance. CONCLUSION: CD may be associated with severe hepatic damage in children and strict GFD may have beneficial effect on the course of liver disease. Serologic screening of CD should be included in differential diagnosis of chronic liver disease of unknown origin.     

Small intestinal bacterial overgrowth in North Indian patients with celiac disease.

BACKGROUND: Occasionally celiac patients continue to experience gastro-intestinal symptoms even with a gluten free diet. In these cases, small intestinal bacterial overgrowth may be one of the causes of the lack of response. Therefore, this prospective study was planned to determine the prevalence of small intestinal bacterial overgrowth in celiac patients. MATERIALS AND METHODS: We studied 87 confirmed cases of celiac disease from North India and 87 age and sex matched controls. Celiac disease was confirmed by positive IgA antitissue transglutaminase on ELISA. 80 g glucose hydrogen breath test (non-invasive test) was performed to establish small intestinal bacterial overgrowth. Rise of more than 10 ppm in hydrogen concentration over baseline value within two hours was considered suggestive of small intestinal bacterial overgrowth. RESULTS: Out of 87 patients with celiac disease, 49 were male and 38 were female.The mean (+/-SD) age for male patients was 26.3 +/- 16.3 years (range 14-59 years) and for female patients was 28.4 +/- 15.6 years (range 16-58 years). Amongst the controls, 52 (59.8%) were male and 35 (40.2%) were female. The mean (+/- SD) age for male controls was 27.6 +/- 14.5 years (range 15-57 years) and for female controls was 29.3 +/- 16.5 years (range 18-59 years). Hydrogen breath test was suggestive of bacterial overgrowth in 18 of the 87 (20.7%) celiac disease patients but not in any of the apparently healthy controls. CONCLUSION: This study indicates that a large number of celiac patients from North India suffer from bacterial overgrowth which can be accordingly treated with antibiotics.     

Serological testing in screening for adult celiac disease.

Assays for celiac-related antibodies are becoming widely available, and the present review aims to clarify the use of these investigations in the diagnosis of, management of and screening for adult celiac disease. The sensitivities and specificities of various antibody tests are discussed, along with their clinical use as an adjunct to small bowel biopsy, and as a first-line investigation for patients with atypical symptoms of celiac disease or patients at high risk of developing sprue.     

Eosinophilic esophagitis in children with celiac disease

Background and Aims:  Eosinophilic esophagitis and celiac disease are distinct gastrointestinal disorders. The present study in children highlights the possible coexistence of these two conditions. This study also analyzes the epidemiological and clinical profiles of these patients.
Methods:  The medical records of patients diagnosed with celiac disease from 1 April 1999 to 31 March 2007 were reviewed. Patients with coincident histological diagnosis of eosinophilic esophagitis were retrospectively identified. The presenting symptoms, laboratory evaluations, endoscopic and histopathological findings, and treatment and follow-up outcomes of these patients were analyzed.
Results:  Of the 221 patients with celiac disease, seven (3.2%) were also diagnosed with eosinophilic esophagitis. A majority (6/7) presented with periumbilical pain and diarrhea. None had dysphagia. Each patient had abnormal celiac screening tests. Three patients had peripheral blood eosinophilia and elevated eosinophil cationic protein. Endoscopic changes of eosinophilic esophagitis and celiac disease were apparent in the majority of patients (6/7). A gluten-free diet was instituted in every patient. Topical corticosteroid therapy was started in one patient at diagnosis and in another patient after repeat endoscopic and histopathological evaluations.
Conclusions:  Awareness of the potential coexistence of eosinophilic esophagitis and celiac disease should promote optimal diagnosis of these conditions. Routine esophageal biopsies may be warranted when investigating for celiac disease.     

Prevalence of associated disorders in Indian patients with celiac disease

Celiac disease (CD) is an immune-mediated disorder that may be associated with various diseases that share a similar pathogenic immune mechanism. This study reports on the prevalence of various diseases in a cohort of CD patients in northern India. Patients diagnosed with CD based on modified ESPGHAN criteria were prospectively evaluated for associated concomitant diseases. Of the 363 patients evaluated, 207 (57.0 %) were male. The mean age was 19 years. Seventy-one percent of patients presented with typical diarrheal disease, while 29 % presented with atypical nondiarrheal disease. One or more associated diseases were noted in 70 (19.2 %) patients. Liver diseases were the most common association. Portal hypertension was present in 33 (9 %) patients; chronic liver disease was the underlying cause in 17 patients, while noncirrhotic causes were noted in 16 patients. Type 1 diabetes was seen in 13 and hypothyroidism in 11 patients. Other unreported or rarely reported associated diseases were also found in some of the patients. Associated comorbid diseases are common, and may need to be actively screened, in Indian CD patients.     

Endoscopic features of celiac disease in children.

BACKGROUND: Endoscopic abnormalities have been described in adult patients with celiac disease that may suggest the diagnosis, especially when the presentation is atypical. METHODS: The duodenum of 140 children undergoing EGD for various different indications was evaluated macroscopically and histologically. RESULTS: Histology revealed total villous atrophy in 80 patients, 79 of whom had celiac disease. Among these, 100% had a mucosal mosaic pattern in the duodenum (sensitivity 98.7%, specificity 96.7%, positive predictive value 97.5%, negative predictive value 98.3%), 70% had scalloped duodenal folds (sensitivity 68.7%, specificity 98.3%, positive predictive value 98.2%, negative predictive value 70.2%), 15% had visible vasculature, and 6% had reduction of duodenal folds. Sensitivity and specificity of endoscopic findings were not modified by chromoendoscopy. Except for the mosaic pattern, the frequency of endoscopic abnormalities increased with age; reduction of duodenal folds was never seen in children with celiac disease who were less than 5 years of age. CONCLUSIONS: The frequency and diagnostic value of endoscopic abnormalities are different in children with celiac disease compared with adults with this disease. Because indications for endoscopy, such as abdominal pain, dyspepsia, and unexplained anemia, can be manifestations of celiac disease, and villous atrophy may have a patchy distribution, awareness of these endoscopic abnormalities is important in the diagnosis of celiac disease in children.     

Serum ghrelin levels in children with celiac disease

OBJECTIVES: Ghrelin, a gastrointestinal hormone, has effects on nutrient intake and growth. Because celiac disease (CD) has intestinal histopathologic alterations and subsequent malnutrition and/or growth failure, we hypothesized that there would be alterations in serum ghrelin levels of those patients. In this study, we aimed to determine serum ghrelin levels in childhood CD, to observe probable alterations under gluten-free diet (GFD), and to see whether there is a relationship between ghrelin levels and the presentation of the disease and/or diet compliance. METHODS: Thirty-six children with CD and 10 healthy children were included. Serum fasting ghrelin level was measured using radioimmunoassay method. After 6 months under GFD, sera of 19 patients were retested for ghrelin level. RESULTS: Mean serum ghrelin levels in children with CD and in controls were 478.2+/-154.6 and 108.3+/-49.1 pg/mL, respectively (P<0.001). Serum ghrelin level was not different in different clinical presentations. Ghrelin was negatively correlated with body mass index, both in healthy children and in children with CD on admission (P<0.01). Ghrelin level was lower after 6 months under GFDcompared with the level detected on admission (P<0.001), but was still higher compared with that of healthy children (P<0.001). Strict diet compliance lowered ghrelin level, although not statistically. CONCLUSIONS: Ghrelin is increased in childhood CD and is responsive to GFD. Further studies are needed to clarify the mechanism underlying its action in CD.     

Update on serologic testing in celiac disease

Contemporary serologic testing has revolutionized the field of celiac disease (CD). Highly accurate serologic assays have shown the prevalence of CD to be nearly 1:100 in many populations. These mostly ELISA (enzyme-linked immunosorbent assay)-based tests allow noninvasive screening and detection. However, the growing number of available serologic tests necessitates reevaluation of their predictive power as a single test or in combination. We review the available tests for CD, including antibodies against gliadin, endomysium, tissue transglutaminase, and deamidated gliadin, and the evidence for preferential use of specific tests in different settings. Despite several novel developments, standardized ELISA-based assays for IgA autoantibodies against tissue transglutaminase remain the test of choice for most populations. We discuss the need to develop tests for CD activity in order to assess the efficacy of upcoming nondietary therapies.     

Gut microflora associated characteristics in children with celiac disease

OBJECTIVES: The aim of the study was to investigate the metabolic function of intestinal microflora in children with celiac disease (CD) in order to find out if there is a deviant gut flora in CD patients compared to healthy controls. METHODS: The study group comprised children with CD, consecutively diagnosed according to current criteria given by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. Thirty-six children were studied at presentation, i.e., on a normal gluten-containing diet, with clinical symptoms and signs indicative of CD, positive celiac serology markers, and a small bowel biopsy showing severe enteropathy. Forty-seven patients were studied when they had been on a gluten-free diet (GFD) for at least 3 months. For comparison, a group of 42 healthy controls (HC) were studied. The functional status of the intestinal microflora was evaluated by gas-liquid chromatography of short chain fatty acids (SCFAs) in fecal samples. RESULTS: There was a significant difference between untreated CD children and HC as well as between treated CD children and HC regarding acetic, i-butyric, i-valeric acid, and total SCFAs. The propionic and n-valeric acids differed significantly between CD children on GFD and HC. Moreover, there was a strong correlation between i-butyric and i-valeric acids in all study groups. CONCLUSIONS: This is the first study of the SCFA pattern in fecal samples from children with CD. The results indicate that there is a difference in the metabolic activity of intestinal microbial flora in children with CD compared to that in HC. The finding of a different pattern of some SCFAs in celiacs both at presentation and during treatment with GFD indicates that it is a genuine phenomenon of CD not affected by either the diet, the inflammation, or the autoimmune status of the patient.     

Serum nitric oxide levels in children with celiac disease

OBJECTIVES: To determine serum nitric oxide levels in pediatric patients with celiac disease and to compare them with the results obtained after 1 year of gluten-free diet. METHODS: We studied serum nitric oxide levels in 41 newly diagnosed patients with celiac disease. Serum levels of nitric oxide were reevaluated after 1 year of gluten-free diet in 23 of them. Mean age was 10.4 +/- 3.4 years (range 2-17 years). RESULTS: The levels of nitric oxide in pretreatment 41 patients with celiac disease and healthy children were detected as 198.33 +/- 20.22 micromol/L and 135.63 +/- 21.17 micromol/L, respectively (P = 0.0001). Serum nitric oxide level, measured in the blood samples 1 year after gluten-free diet, was 148.27 +/- 27.25 micromol/L (P = 0.001). Serum nitric oxide levels were statistically correlated with the degree of histologic changes in celiac disease. In the patients with celiac disease, pretreatment level of nitric oxide was not correlated with the levels of triglyceride, cholesterol, albumin, aspartate aminotransferase, alanine aminotransferase, or creatine kinase. We found correlations with the level of nitric oxide and Hb, mean corpuscular volume, and ferritin. CONCLUSION: Higher serum nitric oxide levels found in children who had not compliance with gluten-free diet suggested the role of serum nitric oxide as an indicator of diet compliance. Because determination of serum nitric oxide is a simple, rapid, cheap, noninvasive, and highly sensitive method for celiac disease, we think that this parameter can be used in the evaluation of diet compliance in children with celiac disease or even instead of gluten challenge, due to more noninvasive property.