Narrow band imaging evaluation of duodenal villi in patients with and without celiac disease:A prospective study

BACKGROUND Duodenal biopsies are commonly obtained during esophagogastroduodenoscopy(EGD) but are very often histopathologically normal. Therefore, a more strategic method for evaluating the duodenal mucosa and avoiding unnecessary biopsies is needed.AIM To examine the clinical utility of narrow band imaging(NBI) for evaluating duodenal villous morphology.METHODS We performed a prospective cohort study of adult patients at Mayo Clinic Rochester from 2013-2014 who were referred for EGD with duodenal biopsies. A staff endoscopist scored, in real-time, the NBI-based appearance of duodenal villi into one of three categories(normal, partial villous atrophy, or complete villous atrophy), captured ≥ 2 representative duodenal NBI images, and obtained mucosal biopsies therein. Images were then scored by an advanced endoscopist and gastroenterology fellow, and biopsies(gold standard) by a pathologist, in a masked fashion using the same three-category classification. Performing endoscopist, advanced endoscopist, and fellow NBI scores were compared to histopathology to calculate performance characteristics [sensitivity, specificity,positive and negative, negative predictive value(NPV), and accuracy]. Inter-rater agreement was assessed with Cohen's kappa.RESULTS112 patients were included. The most common referring indications were dyspepsia(47%), nausea(23%), and suspected celiac disease(14%). Duodenal histopathology scores were: 84% normal, 11% partial atrophy, and 5% complete atrophy. Performing endoscopist NBI scores were 79% normal, 14% partial atrophy, and 6% complete atrophy compared to 91%, 5%, and 4% and 70%, 24%,and 6% for advanced endoscopist and fellow, respectively. NBI performed favorably for all raters, with a notably high(92%-100%) NPV. NBI score agreement was best between performing endoscopist and fellow(κ = 0.65).CONCLUSION NBI facilitates accurate, non-invasive evaluation of duodenal villi. Its high NPV renders it especially useful for foregoing biopsies of histopathologically normal duodenal mucosa.     

Genetic and flow cytometry analysis of seronegative celiac disease: a cohort study

Background: Seronegative celiac disease (CD) poses a diagnostic challenge.

Aims: Characterize and identify differences between seronegative and seropositive CD.

Patients and methods: Retrospective cohort study examining adult patients diagnosed with CD (1980–2017). Clinical, analytical, histological, genetic and immunophenotypic data were compiled. Seronegative CD was defined as a anti-tissue transglutaminase type 2 IgA and endomysial antibodies (EMA) negative and HLA-DQ2 and/or DQ8 positive, showing clinical signs of CD plus an abnormal duodenal biopsy, and responding to a gluten-free diet (GFD). Factors associated with seronegative CD were identified through binomial logistic regression.

Results: Of 315?CD patients, 289 were seropositive (91.7%) and 26 seronegative (8.3%). Among the seronegative patients, higher prevalence was observed for autoimmune thyroiditis (26.9% vs. 9.7%, p?=?.016), HLA-DQ8 heterozygosity (23.1% vs. 2.5%, p???.001) and Marsh I lesion (34.6% vs. 3.7%, p???.001). The two groups showed similar flow cytometry-determined duodenal immunophenotypes and rates of refractory CD.

Conclusions: Seronegative CD differs mostly in genetic (more HLA-DQ8) and histologic (milder atrophy) features as compared with seropositive. Intestinal intraepithelial immunophenotype by flow cytometry, similar in both modalities, is a useful tool to diagnose seronegative CD.     

Prevalence of celiac disease in children with type 1 diabetes: A review

Background and aimsDiabetes mellitus is a chronic disease and a major health threat. Comorbidity of celiac disease and diabetes is associated with many complications in children, and if not diagnosed in time in diabetes children, caused complications, including gastrointestinal disorders, most importantly, growth disorders. Thus, this study aims to summarize the evidence about prevalence of celiac disease in children with type 1 diabetes through a systematic review approach.MethodsA literature review was conducted within databases. Observational studies that assessed the prevalence of celiac disease in diabetes children, were included. We assess the quality of included studies with STROBE checklist. Data extraction and assessment has guided by PRISMA checklist. Also, the data has reported by Garrard’s table.Results31 studies included that assessed 63,349 children with type 1 diabetes. Anemia, osteoporosis, and neurological disorders reported. Studies showed two main type of tests for diagnosis of CD included serological and intestinal biopsy. The prevalence of CD based serologic tests was higher than of intestine biopsy (1.4%–24.5% VS 1.1%–16.6%). In addition, the prevalence of celiac disease was different between populations.ConclusionsCeliac disease is an important comorbidity in children with type 1 diabetes, especially because of the similarity between CD symptoms and neuropathic and gastrointestinal symptoms of diabetes. Screening the diabetes children for celiac disease by serological tests and then intestinal biopsy is recommended.     

Prevalence of celiac disease in Germany:A prospective follow-up study

AIM:To determine the prevalence of celiac disease in a randomly selected population sample. METHODS:A total of 2157 subjects (1036 males; 1121 females) participating in a population-based cross-sectional study underwent laboratory testing for tissue transglutaminase and antibodies to immunoglobulin A, endomysium and antigliadin. In a second step, all subjects who had been examined serologically were surveyed using a questionnaire that included questions specific to celiac disease. Subjects with positive antibody titers and those with histories positive for celiac disease then underwent biopsy. At the first follow up, antibody titers were again determined in these subjects and subjects were questioned regarding symptoms specific for celiac disease and disorders associated with celiac disease. The second follow up consisted of a telephone interview with subjects positive for celiac disease.RESULTS:Antibody tests consistent with celiac disease were reported in eight subjects, corresponding to an overall prevalence of 1:270 (8/2157). The prevalence among women was 1:224 and 1:518 in men. Classical symptoms were observed in 62.5% of subjects. Atypical celiac disease was present in 25.0%, and transient celiac disease in 12.5%. False-negative test results were returned in three subjects. This yields a sensitivity and specificity of 62.5% and 50.0%, respectively, for tissue transglutaminase immunoglobulin-A antibody; of 62.5% and 71.4% respectively, for endomysium antibody; and of 62.5% and 71.4%, respectively, for antigliadin antibody.CONCLUSION:The prevalence rate in our collective lies within the middle tertile of comparable studies in Europe. The use of a single antibody test for screening purposes must be called into question.     

A Brazilian experience of the self transglutaminase-based test for celiac disease case finding and diet monitoring

AIM： To evaluate the effectiveness of a rapid and easy fingertip whole blood point-of-care test for celiac disease （CD） case finding and diet monitoring. METHODS： Three hundred individuals, 206 females （68.7%） and 94 males （31.3%）, were submitted to a rapid and easy immunoglobulin-A-dass fingertip whole blood point-of-care test in the doctor＇s office in order to make immediate clinical decisions： 13 healthy controls, 6 with CD suspicion, 46 treated celiacs, 84 relatives of the celiac patients, 69 patients with dyspepsia, 64 with irritable bowel syndrome （IBS）, 8 with Crohn＇s disease and 9 with other causes of diarrhea. RESULTS： Upper gastrointestinal endoscopy with duodenal biopsies was performed in patients with CD suspicion and in individuals with positive test outcome： in 83.3% （5/6） of the patients with CD suspicion, in 100% of the patients that admitted gluten-free diet transgressions （6/6）, in 3.8% of first-degree relatives （3/79） and in 2.9% of patients with dyspepsia （2/69）. In all these individuals duodenal biopsies confirmed CD （Marsh＇s histological classification）. The studied test showed good correlation with serologic antibodies, endoscopic and histological findings.CONCLUSION： The point-of-care test was as reliable as conventional serological tests in detecting CD cases and in CD diet monitoring.     

Faecal high mobility group box 1 in children with celiac disease: A pilot study

BackgroundCeliac disease (CD) is a gluten-related immunological disorder resulting in inflammatory enteropathy.AimsWe assessed a stool marker of intestinal inflammation, the HMGB1 protein, in children with CD on a gluten free diet (GFD) at baseline and at follow up (FU).MethodsThirty-nine children were investigated at diagnosis and at FU. Traditional serum markers of CD (anti-transglutaminase and anti-endomysial antibodies) and faecal HMGB1 (by enzyme-linked immunosorbent assay and immunoblotting) were tested.ResultsThere was a marked increase at baseline in both serum anti-transglutaminase IgA (anti-tTGAs) and faecal HMGB1; the latter being undetectable in controls. A strong correlation occurred between the two markers. At 12-month FU in 24 patients on GFD, HMGB1 decreased in all subjects, yet still being detectable in six children: high anti-tTGAs where evident in three, while the three with normal anti-tTGAs were complaining of intestinal symptoms and reported a low GFD adherence.ConclusionsFaecal HMGB1 is a valuable marker of intestinal inflammation and may have a role in complementing serology in the management of CD children. Future studies including larger patient cohorts and small bowel mucosa histology will be designed to assess the relationship between faecal HMGB1 levels and duodeno-jejunal histopathology.     

Tissue transglutaminase levels above 100 U/mL and celiac disease: A prospective study

AIM: To investigate whether a tissue-transglutaminase antibody (tTGA) level ≥ 100 U/mL is sufficient for the diagnosis of celiac disease (CD).METHODS: Children suspected of having CD were prospectively included in our study between March 2009 and September 2011. All patients with immune globulin A deficiency and all patients on a gluten-free diet were excluded from the study. Anti-endomysium antibodies (EMA) were detected by means of immunofluorescence using sections of distal monkey esophagus (EUROIMMUN, Luebeck, Germany). Serum anti-tTGA were measured by means of enzyme-linked immunosorbent assay using human recombinant tissue transglutaminase (ELiA Celikey IgA kit Phadia AB, Uppsala, Sweden). The histological slides were graded by a single experienced pathologist using the Marsh classification as modified by Oberhuber. Marsh II and III lesions were considered to be diagnostic for the disease. The positive predictive values (PPVs), negative predictive values (NPVs), sensitivity and specificity of EMA and tTGA along with their 95% CI (for the cut off values > 10 and ≥ 100 U/mL) were calculated using histology as the gold standard for CD.RESULTS: A total of 183 children were included in the study. A total of 70 (38.3%) were male, while 113 (61.7%) were female. The age range was between 1.0 and 17.6 years, and the mean age was 6.2 years. One hundred twenty (65.6%) patients had a small intestinal biopsy diagnostic for the disease; 3 patients had a Marsh II lesion, and 117 patients had a Marsh III lesion. Of the patients without CD, only 4 patients had a Marsh I lesion. Of the 183 patients, 136 patients were positive for EMA, of whom 20 did not have CD, yielding a PPV for EMA of 85% (95% CI: 78%-90%) and a corresponding specificity of 68% (95% CI: 55%-79%). The NPV and specificity for EMA were 91% (95% CI: 79%-97%) and 97% (95% CI: 91%-99%), respectively. Increased levels of tTGA were found in 130 patients, although only 116 patients truly had histological evidence of the disease. The PPV for tTGA was 89% (95% CI: 82%-94%), and the corresponding specificity was 78% (95% CI: 65%-87%). The NPV and sensitivity were 92% (95% CI: 81%-98%) and 97% (95% CI: 91%-99%), respectively. A tTGA level ≥ 100 U/mL was found in 87 (47.5%) patients, all of whom were also positive for EMA. In all these 87 patients, epithelial lesions confirming CD were found, giving a PPV of 100% (95%CI: 95%-100%). The corresponding specificity for this cut-off value was also 100% (95% CI: 93%-100%). Within this group, a total of 83 patients had symptoms, at least gastrointestinal and/or growth retardation. Three patients were asymptomatic but were screened because they belonged to a group at risk for CD (diabetes mellitus type 1 or positive family history). The fourth patient who lacked CD-symptoms was detected by coincidence during an endoscopy performed for gastro-intestinal bleeding.CONCLUSION: This study confirms based on prospective data that a small intestinal biopsy is not necessary for the diagnosis of CD in symptomatic patients with tTGA ≥ 100 U/mL.     

Prevalence,treatments and outcomes of coronary artery disease in Indians: A systematic review

Aim

To conduct a systematic review on the prevalence, risk factors, treatments and outcomes of Coronary Artery Disease (CAD) in Indians.

Methods and results

We conducted a systematic review of studies in Indians with CAD from Jan 1969 to Oct 2012.Initial search yielded 3885 studies and after review 288 observational studies were included. The prevalence of CAD in urban areas was 2.5%–12.6% and in rural areas, 1.4%–4.6%. The prevalence of risk factors was: smoking (8.9–40.5%), hypertension (13.1–36.9%) and diabetes mellitus (0.2–24.0%). The median time to reach hospital after an MI was 360 min. In hospital rates of drug use were: antiplatelets 68%–97.9%, beta blockers 47.3%–65.8% and ACEIs 27.8–56.8%.

Conclusions

In this first systematic review of CAD in India, prevalence of risk factors is high, treatments delayed and use of evidence based treatments variable.     

L-Carnitine in the treatment of fatigue in adult celiac disease patients: A pilot study

BACKGROUND: Fatigue is common in celiac disease. L-Carnitine blood levels are low in untreated celiac disease. L-Carnitine therapy was shown to improve muscular fatigue in several diseases. AIM: To evaluate the effect of L-carnitine treatment in fatigue in adult celiac patients. METHODS: Randomised double-blind versus placebo parallel study. Thirty celiac disease patients received 2 g daily, 180 days (L-carnitine group) and 30 were assigned to the placebo group (P group). The patients underwent clinical investigation and questionnaires (Scott-Huskisson Visual Analogue Scale for Asthenia, Verbal Scale for Asthenia, Zung Depression Scale, SF-36 Health Status Survey, EuroQoL). OCTN2 levels, the specific carnitine transporter, were detected in intestinal tissue. RESULTS: Fatigue measured by Scott-Huskisson Visual Analogue Scale for Asthenia was significantly reduced in the L-carnitine group compared with the placebo group (p=0.0021). OCTN2 was decreased in celiac patients when compared to normal subjects (-134.67% in jejunum), and increased after diet in both celiac disease treatments. The other scales used did not show any significant difference between the two celiac disease treatment groups. CONCLUSION: L-Carnitine therapy is safe and effective in ameliorating fatigue in celiac disease. Since L-carnitine is involved in muscle energy production its decreased absorption due to OCTN2 reduction might explain muscular symptoms in celiac disease patients. The diet-induced OCTN2 increase, improving carnitine absorption, might explain the L-carnitine treatment efficacy.     

Hepatitis B vaccine in celiac disease:Yesterday,today and tomorrow

Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV).The non-responsiveness to HBV vaccine has also been described in healthy people,nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls.Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described,such as the genetic hypothesis,according with CD patients carrying the disease-specific haplotype HLA-B8,DR3,and DQ2,show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype.On the other hand,it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine.Moreover,it has been demonstrated a possible genetic predisposition to hepatitis B vaccine nonresponsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokinereceptors and toll like receptors,but the pathogenic mechanism responsible for this low responsiveness still remains unclear.The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients.     

Systemic lupus erythematosus,celiac disease and antiphospholipid antibody syndrome: a rare association

Association of celiac disease with systemic lupus erythematosus is rare, even though HLA B8 and DR3 are commonly associated with these diseases. We read with great interest a similar case reported by Hrycek and Siekiera in this journal and wish to highlight another case of ours, which had celiac disease, systemic lupus erythematosus and antiphospholipid antibody syndrome, an association which has never been described before.     

Quality of life of Moroccan patients with celiac disease: Arabic translation,cross-cultural adaptation,and validation of the celiac disease questionnaire

Background and study aimsCeliac disease (CD) management is based on a lifelong gluten-free diet (GFD) that affects the quality of life (QoL) of patients with CD. Specific instruments have been used to evaluate this QoL, such as the CD-Questionnaire (CD-Q). This study aimed to translate, validate, and cross-culturally adapt the CD-Q in an Arabic version and then apply it to evaluate the QoL of Moroccan adult patients with CD.Patients and methodsThe Moroccan version of the CD-Q (M?CD?Q) was administered to 150 patients with CD, and 112 of them completed it. The reproducibility and reliability of the M?CD?Q were studied by the intraclass coefficient (ICC) and Cronbach’s α, respectively. Parametric and nonparametric tests, confirmatory factor analysis, and Spearman correlation were used for the statistical analysis performed by SPSS, and the goodness-of-fit test was determined using SPSS AMOS.ResultsNo difficulties were found during the translation and cultural adaptation of the CD-Q. Cronbach’s α showed good internal consistency. The retest showed excellent reproducibility (ICC > 0.4). The study of the psychometric properties of the M?CD?Q showed good acceptance, zero ceiling effect, and floor effect. The model fit was good [(root mean square error of approximation = 0.075 (<0.08) and χ2 = 509.04, p < 0.001]. The total scores showed a neutral QoL. This QoL was worse in the worries subscale, which is related to gluten-free products. The GFD did not improve the QoL of the examined samples.ConclusionThe M?CD?Q is the first reliable and adapted instrument in an Arab country for the evaluation of QoL in patients with CD. CD negatively influences this QoL, especially items related to gluten-free products.     

Low incidence but poor prognosis of complicated coeliac disease: A retrospective multicentre study

BackgroundCoeliac disease is a chronic enteropathy characterized by an increased mortality caused by its complications, mainly refractory coeliac disease, small bowel carcinoma and abdominal lymphoma. Aim of the study was to study the epidemiology of complications in patients with coeliac disease.MethodsRetrospective multicenter case–control study based on collection of clinical and laboratory data. The incidence of complicated coeliac disease was studied among coeliac patients directly diagnosed in four Italian centres. Patients referred to these centres after a diagnosis of coeliac disease and/or complicated coeliac disease in other hospitals were therefore excluded.ResultsBetween 1/1999 and 10/2011, 1840 adult coeliac patients were followed up for 7364.3 person-years. Fourteen developed complications. Since five patients died, at the end of the observation period (10/2011), the prevalence of complicated coeliac disease was 9/1835 (1/204, 0.49%, 95% CI 0.2–0.9%). The annual incidence of complicated coeliac disease in the study period was 14/7364 (0.2%, 95% CI 0.1–0.31%). Although complications tend to occur soon after the diagnosis of coeliac disease, Kaplan–Meier curve analysis showed that they can actually occur at any time after the diagnosis of coeliac disease.ConclusionsComplications of coeliac disease in our cohort were quite rare, though characterised by a very high mortality.     

Holmes-Adie syndrome, autoimmune hepatitis and celiac disease： A case report

A 35-year-old female patient presented with the following symptoms of Holmes-Adie syndrome: photophobia, enlargement of the left pupil unresponsive to light, Achilles areflexia. The pilocarpine test was positive. No tumor or other neurological abnormality was found. She had a 19-year history of autoimmune hepatitis. Flares up were observed following each 3 deliveries. At age of 31 she presented with diarrhea and weight loss. Abdominal tumor was detected by ultrasound. The surgically removed tumor was histologically a benign mesenteric multicystic lymphangioma. Simultaneously, celiac disease was diagnosed. Gluten-free diet resulted in a significant improvement of celiac disease, but not of autoimmune hepatitis. Autonomic neuropathy was proven by standard cardiovascular tests. The patient was a homozygous carrier for HLA DQ2 antigen characteristic for celiac disease and heterozygous for HLA DR3 B8 frequent in autoimmune liver diseases. Our novel observation on association of Holmes-Adie syndrome with autoimmune hepatitis and celiac disease is suggestive for a common immunological background for all three entities present in a patient with mesenteric multicystic lymphangioma.     

Celiac disease: Prevalence, diagnosis, pathogenesis and treatment

Celiac disease(CD) is one of the most common diseases,resulting from both environmental(gluten) and genetic factors [human leukocyte antigen(HLA) and nonHLA genes].The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world.However,the population with diabetes,autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD,at least in part,because of shared HLA typing.Gliadin gains access to the basal surface of the epithelium,and interact directly with the immune system,via both trans-and para-cellular routes.From a diagnostic perspective,symptoms may be viewed as either "typical" or "atypical".In both positive serological screening results suggestive of CD,should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet(GFD) to confirm the diagnosis.Positive anti-tissue transglutaminase antibody or antiendomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy.Currently,the only treatment available for CD individuals is a strict life-long GFD.A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide,prevent toxic gliadin peptide absorption,blockage of selective deamidation of specific glutamine residues by tissue,restore immune tolerance towards gluten,modulation of immune response to dietary gliadin,and restoration of intestinal architecture.