Positive EMA Research Articles

Endomysial antibodies or anti-tissue transglutaminase type 2 IgA antibodies as a confirmatory test in children with celiac disease.

The no-biopsy approach to diagnose celiac disease (CD), introduced in the 2012 European Society for Gastroenterology and Hepatology and Nutrition guidelines, requires an anti-endomysial antibody (EMA) confirmatory serology test following a high-positive immunoglobulin A anti-tissue transglutaminase-2 (anti-TG2) antibody ≥10 times the upper limit of normal (ULN). The aim of this retrospective study is to compare EMA positivity and high-positive anti-TG2 in patients who had their confirmatory test within two month of their first high-positiveanti-TG2 test. Among 933 patients who had high-positive anti-TG2 serology more than 10 times the ULN in their first sample, all had both high-positive anti-TG2 and positive EMA, most of them with very high EMA titers (99.6%) in their confirmatory test. In conclusion, we suggest that a repeated anti-TG2 test can replace the EMA test as the confirmatory serology test for the confirmation of the diagnosis of CD in the no-biopsy approach.

A170 A RARE CASE OF CELIAC DISEASE WITH PULMONARY HEMOSIDEROSIS AND DILATED CARDIOMYOPATHY

Abstract Background Celiac disease (CD) is a primary disease of the intestine but patients also present with extra intestinal manifestations like iron deficiency anemia, dermatitis herpetiformis, selective IgA deficiency, thyroid disorders, diabetes mellitus and various connective tissue disorders but rarely with pulmonary hemosiderosis and dilated cardiomyopathy. Aims We present a rare case of CD associated with pulmonary hemosiderosis and dilated cardiomyopathy in a 10 year old child. Methods Patient interview and chart review was conducted. Literature reveiw was performed using pub med data base. Results A 10 year old presented with a 1 day of cough and hemoptysis. His past medical history includes Constipation and low percentile for weight and height. His first cousin is recently diagnosed with celiac disease, otherwise his family history is unremarkable. He is pale on exam and has a BMI of 13.64 which is ampersand:003C1% for age. He had fine crackles on bilateral lung fields but no signs of respiratory distress. His pericardium was active but no murmur or gallop. CXR showed cardiomegaly and Echo was suggestive of dilated cardiomyopathy. ECG was significant for LBBB. Chest CT showed bilateral confluent symmetric ground glass densities with possibility of pulmonary hemosiderosis. His blood work was significant for iron deficiency anemia, low selenium of 0.94umol/L and zinc 8.4umol/L. His antibody screen was positive for ANA, a tTGA of ampersand:003E4,965.5 and positive EMA. The cardiomyopathy and pulmonary hemosiderosis in this case are considered to be secondary findings as both have been reported in the context of celiac disease and patient was initiated on gluten free diet (GFD). Patient was blood transfused and kept on oral iron and multivitamins. He was also started on aldactazide 1 tab daily, 20mg twice daily enteresto and carvedilol 3.125mg twice daily as part of his heart failure management. At one month follow up, patient was having abdominal discomfort due to his constipation and follow up labs showed improvement of his anemia. Conclusions Patients with pulmonary hemosiderosis occuring with CD demonstrate improvement of their symptoms with GFD highlighting the importance of screening all pulmonary hemosiderosis patients for CD. Cardiomyopathy associated with celiac disease is also another very rare occurrence and only few studies have been reported so far. In conclusion, although a rare occurrence, the association of CD with pulmonary hemosiderosis and cardiomyopathy has huge therapeutic implications emphasizing the need to have high index of suspicion and routine screening for CD among patients with pulmonary hemosiderosis and dilated cardiomyopathy. Funding Agencies The hospital for sick children/sick kids hospital

Papillary renal neoplasm with reverse polarity: a clinicopathologic study of 43 cases with a focus on the expression of KRAS signaling pathway downstream effectors

Papillary renal neoplasm with reverse polarity (PRNRP) is a renal tumor with frequent KRAS mutations. In this study, we aimed to report the clinical, histological, and immunohistochemical characteristics of PRNRP and the protein expression of various KRAS signaling pathway downstream effectors in PRNRP. PRNRP samples from patients who underwent surgical resection at Seoul National University Hospital over an 11-year period (January 2011 to December 2021) were analyzed. We identified 43 PRNRPs, defined as papillary renal tumors with a thin papillary architecture, eosinophilic finely granular cytoplasm, and apical nuclear position. Immunohistochemistry revealed typical characteristics of PRNRP, including exclusively positive GATA3 (43/43); highly positive L1CAM (43/43), PAX8 (43/43), and EMA (43/43); and low positive AMACR (4/43), RCC (1/43), and vimentin (1/43). KRAS signaling pathway effectors, such as p-ERK, RalA, and RalB, were highly expressed in PRNRP compared to papillary renal cell carcinoma (pRCC) with low or high nuclear grade (P<.001, all). Compared to pRCC with high nuclear grade, patients with PRNRP exhibited significantly longer progression-free survival (P<.001). PRNRP showed the best clinical outcome, with no disease progression in any of the cases. Our study analyzed the largest number of PRNRP cases and is the first to analyze the association between PRNRP and the KRAS downstream signaling pathway. PRNRP was found at a high frequency among all papillary renal tumors (43/207) and demonstrated a very good prognosis. PRNRP showed high GATA3, L1CAM, PAX8, and EMA protein expression as well as high p-ERK, RalA, and RalB protein expression.

P6-4 Case report: Malignant priapism secondary to adrenal sarcoma

A 68-year-old man with history of DM type II, and BPH. In Mar 2019, he presented with right-sided abdominal mass. Abdominal CT scans showed right multiple internal septate cystic adrenal mass with 15.2 cm in sized. Right adrenalectomy and nephrectomy were done. Pathology reports showed a malignant epithelioid neoplasm with free margin, found tumor necrosis and mitosis 5/50 HPF. IHC showed positive CD56, NSE, CAM5.2, EMA, Vimentin, SMA, CD31, ERG, FLI-1, MDM2 and negative for synaptophysin, chromogranin, GFAP, S100, AE1/AE3, PAX8, Inhibin, MelanA, HMB45, Desmin, and Calponin.

Clinical Characteristics and Outcomes of Patients with Positive Celiac Serology and Cancer Therapy Exposure.

Objectives: The prevalence of celiac disease (CD) among cancer patients is unknown, yet new cases of CD occur after cancer therapy exposure. The aim of this study was to describe the clinical course and endoscopic features of patients with positive celiac serology (PCS) post-cancer therapy exposure (PCTE) as compared to those with no cancer therapy exposure (NCTE).Methods: A retrospective study of adult patients with PCS at MD Anderson Cancer Center between March 2009 and May 2020. Patients with positive tTG IgA, tTG IgG, and/or EMA IgA were categorized into cases with NCTE and PCTE. Clinical course, endoscopic and histologic features, and treatments were compared between the two groups.Results: Of the 4,345 patients screened for celiac serology, 21 (0.5%) met inclusion criteria. 12 were PCTE, with a median time of 258 days (173-930 days) from initiation of the last cancer therapy. Those PCTE had a higher rate of diarrhea (75% vs 22%, p = 0.030), malnutrition and death. A gluten-free diet was initiated in 82% PCTE vs 89% NCTE, with the majority experiencing symptom resolution. There were no significant differences in endoscopic and histologic features. 17 patients met criteria for CD diagnosis.Conclusions: Our findings suggest that CD may be under-diagnosed in cancer patients. Patients with PCS after cancer therapy may present with diarrhea, nutritional deficiencies, and malnutrition, yet a gluten-free diet may be efficacious in treatment management. Therefore, CD should be considered when treating cancer patients. Given the relative proximity of PCS to cancer therapy exposure, future studies should investigate the association of cancer and cancer therapy with the development of CD.

PNS139 Single Arm Trials: Route to Success Despite Increasing Demands for Evidence – an Analysis Based on the Prismaccess Database

Despite increasing demand from regulators and payers to increase the evidence quality in submissions, assessments lacking comparative trial data remain common at the regulatory and HTA level. This research identifies the HTA outcome success across the EU5 (TC, G-BA, NICE, AIFA, AEMPS) following EMA marketing approval using only non-comparative data. Using Prismaccess, EMA approvals from 1st Jan 2015 to 24th Apr 2020 were extracted with their EU5 outcomes. Submissions were excluded if the EPAR was not available or the NCT number of phase II or III trials could not be identified. In the case of HTA resubmissions, the latest decision was considered in the analysis. The highest rating was considered if an HTA body assessed several sub-populations. Between 2015-2019, 49 positive EMA assessments using only single arm trials were identified from 46 different products. At the EMA, 22/49 (44.9%) assessments were for the first indication of a product, 21/49 (42.9%) assessments were for oncological indications, and 21/49 (42.9%) assessments were for orphan products (at the time of EMA assessment). Cancer and orphan therapies proportionally received a more favorable outcome at each of the EU5 HTA bodies than non-cancer and non-orphan products. A majority (10/12; 83.3%) of orphan assessments completed at the G-BA were awarded non-quantifiable added benefit. These results show that cancer and orphan products submitted at the EMA with single arm trials tend to receive better HTA outcomes than non-cancer and non-orphan products. This could be due to a greater unmet need in cancer and orphan indications, resulting in greater flexibility from HTA bodies. The large proportion of orphan assessments awarded non-quantifiable added benefit at the G-BA is likely to be influenced by the automatic legal provision of additional benefit when the annual turnover is less than €50m.

Should we worry about the eyes of celiac patients?

In this article, we evaluate subfoveal choroidal thickness in celiac patients with respect to adherence to the gluten-free diet and nonadherence to the gluten-free diet, comparing with age and sex matched healthy controls using spectral-domain optical coherence tomography. A case-control study among 42 celiac patients and 42 healthy participants was conducted in the Department of Pediatric Gastroenterology. Celiac patients of our policlinics compliant with spectral-domain optical coherence tomography examination enrolled in the study. Celiac patients had been asked verbally about their adherence to gluten-free diet, were evaluated according to negative or positive EmA and anti-TG2 for defining adherence, and were divided into two groups (adherence to gluten-free diet and nonadherence to gluten-free diet). Subfoveal choroidal thickness was thinner in EmA (+) or anti-TG2 (+) eyes than EmA(-) or anti-TG2 (-) eyes in celiac patients, but it was not statistically significant. The mean subfoveal choroidal thickness values in eyes with celiac disease, whose diagnosis time was longer than 60 months, were thinner than shorter group. Longer duration of gluten-free diet was associated with adherence difficulty and thinner choroidal thickness (r = -0.15, p = 0.34). Adherence to gluten-free diet was 88.2% for children below the age of 60 months and 57.1% for children older than 60 months. In conclusion, in addition to other extraintestinal manifestations of celiac disease, diagnosis time longer than 60 months in pediatric celiac patients, nonadherence to the gluten-free diet, and antibody positivity should be focused on during ophthalmologic examination and choroid measurement.

Serological screening for coeliac disease in patients with juvenile idiopathic arthritis

Background and study aimsJuvenile idiopathic arthritis (JIA) is characterized by autoimmune aetiology. A gene locus 4q27 related to rheumatoid arthritis, psoriatic arthritis, and coeliac disease is associated with susceptibility to JIA. There are reports indicating several patients with JIA had been diagnosed with CD. We aimed to assess the frequency of coeliac disease (CD) in patients with juvenile idiopathic arthritis (JIA). Patients and methodsThis prospective study was carried out from October 2015 to August 2016 and included 96 patients with JIA. All patients were evaluated in terms of clinical and laboratory findings of CD. Levels of total IgA and tissue transglutaminase antibody (tTG) IgA were measured in all patients. Those with increased level of tTG IgA were further tested for anti-endomysium IgA antibodies (EMA). Gastroduodenoscopy were planned for a definite diagnosis of CD in patients with positive EMA. ResultsOf the 96 patients in our study, 34 (35.4%) had oligoarticular form of JIA, 29 (30.2%) had polyarticular form, 12 (12.5%) had ERA form, 11 (11.5%) had systemic form, and 10 (10.4%) had psoriatic form. Sixteen of our patients (16.6%) were not using any drugs during the study. Neither EMA IgA antibodies were analysed nor gastro-duodenoscopy was performed because no patients were positive for tTG IgA. There was no difference in terms of tTG levels between the patients using NSAIDs or other drugs. ConclusionWe did not find CD in children with JIA. Long term studies with more JIA patients are needed to provide more precise interpretation.

SEROLOGICAL SCREENING FOR CELIAC DISEASE IN CHILDREN WITH COLCHICINE-RESISTANT FAMILIAL MEDITERRANEAN FEVER

Familial Mediterranean fever and celiac disease share some common clinical features such as abdominal pain, diarrhea, arthralgia and arthritis. Also, both of the diseases are associated with many inflammatory and autoimmune diseases. Previous studies have shown the association between familial Mediterranean fever (FMF) and different clinical conditions. We aimed to investigate the relationship between celiac disease and colchicine-resistant familial Mediterranean fever (crFMF) disease. This prospective study was conducted at the Department of Pediatric Gastroenterology and Pediatric Rheumatology from October 2015 to August 2016. A total of 24 patients with crFMF were included in the study. We used 60 sex- and age-matched healthy subjects as a control group. Levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in both groups. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Gastroduodenoscopy and intestinal biopsy were planned for a definite diagnosis of celiac disease in patients with positive EMA. Of the 24 patients in this study, 18 (75.0%) were female. Only 4 (16.6%) of 24 patients were positive for tTG IgA. Patients with positive tTG IgA were then tested for EMA IgA antibodies and none of them had a positive result. Only one (1.6%) subject from the control group was positive for tTG IgA but EMA positivity was not detected. We did not found celiac disease in 24 children with crFMF. Since crFMF disease is rarely seen in general population, further studies with more patients are needed to provide more precise interpretation.

The association between coeliac disease and periodontitis: Results from NHANES 2009-2012.

To investigate whether coeliac disease (CD) was associated with periodontitis among a nationally representative sample of US adults. The National Health and Nutrition Examination Survey (NHANES) 2009-2012 enrolled 6,661 subjects with full-mouth periodontal examination and serological testing for antitissue transglutaminase (tTg) and antiendomysial (EMA) antibodies. CD was defined as (i) self-reported physician diagnosis while on a gluten-free diet; or (ii) tTg levels >10.0U/ml and positive EMA results. Positive serology without self-reported diagnosis was defined as undiagnosed CD (UdxCD). Periodontitis was defined according to the CDC/AAP definition. Multivariable linear and logistic models were used to regress the mean probing depth (PD) or attachment loss (AL) outcomes across CD categories (none, diagnosed and undiagnosed). The prevalence of moderate/severe periodontitis and diagnosed/undiagnosed CD was 40% and 0.74%, respectively. Mean AL was lower among those with CD although results were not statistically significant (p=.67). The odds of periodontitis among individuals with diagnosed and undiagnosed CD were: 0.5(0.22, 1.16) and 0.62(0.1, 3.75), respectively. Mean PD levels among those without CD or with diagnosed or undiagnosed CD were 1.49±0.02, 1.36±0.11 and 1.31±0.11 (p=.03). CD is associated with modestly lower levels of mean PD but was not associated with mean AL or periodontitis. Larger studies are necessary to enhance precision and strengthen conclusions.

Mass Screening for Celiac Disease Among School-aged Children: Toward Exploring Celiac Iceberg in Saudi Arabia

We conducted this mass screening study to determine the prevalence of celiac disease (CD) and characterize the celiac iceberg among Saudi pediatric population in Riyadh, the capital city of Saudi Arabia. During the study period (January 2014-June 2016), we have conducted a cross-sectional, mass screening, immunoglobulin A-tissue transglutaminase (TTG-IgA)-based study on 7930 Saudi students from primary and intermediate schools in Riyadh. Students with positive TTG-IgA (>20 U/L) were called in the hospital to undergo a repeat of TTG-IgA; in those with borderline positive TTG-IgA (20-60 U/L), IgA-endomyseal antibody (EMA-IgA) test was performed. Children with TTG-IgA >60 U/L and children with borderline positive TTG-IgA and positive EMA-IgA were advised to undergo upper endoscopy and intestinal biopsies. We identified 221 students with positive TTG-IgA (2.8%). CD was diagnosed in 119 cases (1.5%, 1:67 Saudi children) (mean age 11.5 ± 2.62 years; girls 81 [68%]). Another 51 children had persistently borderline positive TTG-IgA but negative EMA (0.64%) and the remaining 51 had transiently positive TTG-IgA. We have identified 3 clinical patterns in the screening-identified cases with CD: a silent form (37%), a mild symptomatic form characterized by gastrointestinal symptoms in presence of normal growth or overweight/obesity (48%), and gastrointestinal symptoms associated with impaired growth in 15%. Our study provided evidence of a high prevalence of CD among Saudi children (1.5%), a rate that is at least twice the average prevalence rate in Europe and North America.

The Role of Serological Testing and HLA Genotyping in the Diagnosis of Celiac Disease in Slovak Cohort. Can Duodenal Biopsies be Omitted

Presented analysis focuses on usefulness of consecutive celiac disease antibodies testing anti-TG2 and EMA, and HLA-DQ2/DQ8 genotyping in symptomatic children and adolescents with suspected celiac disease refered to the latest ESPGHAN guidelines (2012), that permit confirmation of celiac disease without previous duodenal biopsy. A total of 258 children and adolescents (86 male and 172 girls), aged 2 to 18 years, were retrospectively examined performance of celiac disease testing according national guidelines from 2009 included duodenal sampling and the ESPGHAN nonbiopsy criteria in a pediatric population. In applying nonbiopsy criteria to our cohort, 33,3 % (86) of symptomatic children and adolescents with such high anti-TG2 titers and positive EMA could have been initially diagnosed without an intestinal biopsy. All of them presented with advanced intestinal atrophy Marsh 2-3. Part of the rational of the study was to determine sensitivity and specificity, positive and negative predictive values of the final laboratory tests and diagnostic accuracy of the combined tests for antibodies.

Omitting duodenal biopsy in children with suspected celiac disease and extra-intestinal symptoms

BackgroundThe aim of our study is to evaluate if in children with highly positive serology and HLA-DQ2/DQ8 (triple test, TT) and only extra-intestinal symptoms, it is possible to omit performing an intestinal biopsy for celiac disease (CD) diagnosis, as suggested by the new European Society for Pediatric Gastroenterology, Hepatology and Nutrition ESPGHAN guidelines.MethodsIn this retrospective study a total of 105 patients, suspected of having CD because of extra-intestinal symptoms and showing serum tissue transglutaminase antibody (anti-tTG) and anti-endomysial antibody (EMA) measurements and HLA genotyping, were considered for the final analysis (33 boys and 72 girls; age range 1.5–17.6 years).ResultsHistological findings confirmed diagnosis of CD in 97 (92.4%) patients. Forty-one patients (39%) showed anti-tTG >10 times normal values, positive EMA and positive HLA-DQ2/DQ8 (positive TT). All of them had a diagnosis of CD, therefore there were no false positive cases. Sixty-four patients were negative for the TT. In eight cases, CD was ruled out and these were considered true negative cases. In the remaining 56 negative TT patients, intestinal biopsy confirmed CD diagnosis and they were considered false negatives. Based on these results, specificity for the TT was 100% and sensitivity was 42.3%.ConclusionsOn the basis of the present study, diagnosis of CD can be reliably performed without a duodenal biopsy in children with only extra-intestinal symptoms.

Screening for celiac disease, by endomysial antibodies, in patients with unexplained hypertransaminasaemia

Objective: To do a serological screening for celiac disease in patients with unexplained liver cytolysis.Materials and methods: Fifty-six patients with liver cytolysis without known aetiology were studied. Endomysial antibodies were determined by indirect immunofluorescence on human umbilical cord. Two thousand and five hundred blood donors served as control group. For statistical analysis, we used Chi-square or Fisher’s exact test.Results: The frequency of IgA endomysial antibodies in our patients was significantly higher than in the control group (8.92% vs. 0.28%, p < .001). In female, endomysial antibodies were significantly more frequent in patients than in healthy subjects (12.12% vs. 0.4%; p < .001). In male, endomysial antibodies were significantly more frequent in patients than in healthy subjects (4.34% vs. 0.22%; p = .006). The frequency of positive EMA in female patients was higher than in male, but the difference was not statistically significant (12.12% vs. 4.43%; p = .6). Two patients were non-compliant with the gluten-free diet. One patient was out of touch. For the two other patients, transaminase levels reverted to normal level within six months of strict gluten withdrawal.Conclusions: A screening for celiac disease should be included within the diagnosis protocol of liver cytolysis.

The effects of modified versus unmodified wheat gluten administration in patients with celiac disease

Celiac disease (CD) treatment requires a gluten-free diet (GFD), although alternative approaches have been proposed. Modification of gliadin peptides using microbial transglutaminase (mTG) inhibits their ability to induce immune response in vitro. Our aim was to evaluate the safety of mTG-modified wheat flour ingestion in CD patients. Twenty-one CD patients in remission were randomized to receive mTG-modified (n=11) or unmodified (n=10) wheat flour rusks, in double-blind fashion. Monthly, patients completed a symptom questionnaire. Serum anti-tTG, EMA and creatinine levels were monitored. At baseline and after 90days, serum anti-actin antibodies (AAA) were measured and upper endoscopy was performed. Data were analyzed by non-parametric tests. 7/11 patients eating modified rusks and 7/10 patients receiving unmodified rusks completed the study. At baseline, all patients showed negative serum anti-tTG and EMA results. At the end, 2/7 (28.6%) patients ingesting modified and 4/7 (57.1%) patients taking unmodified rusks presented positive serum anti-tTG and EMA results. Creatinine results were unmodified. Moreover, 1/7 (14.3%) patients ingesting modified and 4/7 (57.1%) patients taking unmodified rusks presented villous atrophy. In patients who received unmodified rusks, the AAA levels increased significantly and duodenal anti-tTG levels appeared higher than those measured in patients who ate modified rusks. Abdominal swelling, bloating and nausea were more severe in patients ingesting unmodified rusks than those taking modified rusks. Our results may support larger clinical trials to confirm the enzymatic treatment of wheat flour as an alternative to GFD.Clinicaltrials.gov registration no: NCT02472119.

The great imitator - EMA positive glioblastoma multiforme

Introduction: Glioblastoma multiforme (GBM) has always been a diagnostic challenge for pathologists. As a rare oncological entry, originating from the astrocytic glia, can manifest itself in a variety of histomorphological forms, mimic other tumors and often gives a varying immunohistochemical (IHC) profile further challenging the process of its verification. Material and Methods: Four pathologically verified cases of GBM, registered at the “St. Marina” University Hospital, Varna, Bulgaria were retrieved from the central pathological archive. The cases were tested and reviewed based on their hematoxylin and eosin (H&E) profiles and immunohistochemical reactions with GFAP used a glial differenciation marker, Vimentin used as a positive IHC control and EMA, an epithelial marker, non-reactive in healthy brain tissue. Results: As expected all GBM cases had the histomorphological hallmarks of the tumor on the H&E stain and were diagnostically positive for GFAP and gave a strong positive IHC reaction with Vimentin. Three out of the four cases also revealed a varying in intensity reaction with EMA, with one case giving a weak reaction in individual cells that could not be considered diagnostic and the other two cases giving a diffuse positive reaction in most of the tumor cells. Conclusion: In the age of immunohistochemistry, GBM continues to expand the set of IHC markers that give a reaction with it, although several them such as Cytokeratin AE1/AE3 and EMA, as demonstrated in this study, should be non-reacting as they react with proteins normally present only in epithelial cells and absent in healthy brain tissue. This can often be misleading and in certain cases, lead to histopathological misdiagnosis.

The frequency of the celiac disease among children with familial Mediterranean fever

We aimed to assess the frequency of celiac disease (CD) in patients with Familial Mediterranean Fever (FMF). This prospective study was carried out from October 2015 to March 2016 and included 303 patients with FMF. We used 98 sex- and age-matched healthy subjects as a control group. Levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in all groups. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Patients with positive EMA underwent gastro-duodenoscopy and intestinal biopsy for a definite diagnosis of CD. Only 9 of 303 patients (2.9%) were positive for tTG IgA. Patients positive for tTG IgA were then tested for EMA and only one of them (0.3%) had a positive result. This patient underwent gastro-duodenoscopy. The pathological report was compatible with Marsh 0 classification score for the diagnosis of CD. Two subjects from the control group were positive for tTG IgA but none of them had positive EMA antibodies. We did not find CD in the large cohort of childhood FMF patients. The prevalence of CD did not show association with presence of childhood FMF in this study and CD would not be a considerable complication of childhood FMF.

PWE-052 Auditing The Diagnostic Process of Coeliac Disease in Paediatrics

Introduction The management of coeliac disease (CD) is clear, however agreement on paediatric diagnosis is debated. NICE dictates that TTG testing should be used front line, with EMA added if TTG is borderline, and referral to a specialist for a final diagnosis. ESPGHAN states that symptomatic patients with TTG > 10 times the upper limit (ULN) will most likely have villous atrophy and recommends the use of HLA DQ2/DQ8 as a rule in test to obviate the need for a biopsy. This audit reviewed our adherence to these guidelines over 4 years and investigated the reliability of serological and genetic testing as indicators of CD. Methods TTG positive data (>7.0 kU/L) in those Results Of the 34 patients, 28 were diagnosed with CD. 13 underwent a biopsy; 12 were positive and 1 was negative, most likely due to a GFD. 11 nonbiopsied patients underwent HLA testing; all 11 were positive. 4 had neither biopsy or HLA testing; 2 were diagnosed on positive TTG and EMA results, 1 was diagnosed on symptoms and a high TTG, and 1 was diagnosed on TTG alone, due to a biopsy refusal. The average dietician referral time post initial TTG was 164 days; 122 days for those undergoing HLA testing and 220 days for those undergoing a biopsy. Of the remaining patients, 4 were not diagnosed with CD and their average TTG = 13.4 kU/L; 2 had normal EMA results, 1 had a negative biopsy, and 1 had a normal repeat TTG. Of all patients, 24 had TTG > 10 ULN; 22 were diagnosed with CD, and 2 had early CD, but a GFD was not instigated. 1 was asymptomatic and did not consent to a biopsy, and 1 had a positive EMA and was awaiting HLA testing. 10 patients had TTG Conclusion TTG was always used front line, but EMA was not assessed in all borderline cases. Symptomatic patients with TTG > 10 ULN, regardless of biopsy or HLA testing, were diagnosed with CD or early CD. HLA testing was not always utilised, with 46% of cases having a biopsy, however in all instances of HLA testing this occurred to obviate a biopsy. There is no indication of a minimum referral time to a dietician in the guidelines, but referral times are longer in those who underwent a biopsy, with the need to maintain a normal diet. The diagnostic process of CD is becoming streamlined as more consultants opt for serological and genetic testing, allowing for quicker management. Disclosure of Interest None Declared

Screening for Coeliac Disease: Are We Good at It?

Department of Paediatrics, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland Coeliac disease (CD) is an immune reaction to gluten in genetically predisposed subjects. CD is likely to affect approximately 1% of the population of England [1]. The age of presentation is influenced by the age of introduction of gluten into the diet. CD may present as a large variety of non-specific signs and symptoms. Children with CD may experience unexplained poor growth following the introduction of gluten, delay puberty, abnormal stools and constipation. General irritability, chronic abdominal pain, abnormal liver biochemistry, abdominal distension and buttock wasting have been reported. CD should be considered in children presented with iron deficiency anaemia, growth failure with or without gastrointestinal symptoms. Patients with CD may experience low bone mineral density [2], but similar health-related quality of life as their peers without CD [3]. However individuals with CD may exhibit no symptoms. Certain individuals are at an increased risk; such as patients with type 1 diabetes mellitus, Down’s syndrome and Turner’s syndrome, for example, and presymptomatic screening is advised [4]. Diagnosis can be confirmed by flat mucosa on jejunal biopsy followed by the resolution of symptoms and catch up growth upon gluten withdrawal. Diagnostic serological tests have been developed. These’s include IgA anti-tissue transglutaminase (IgA-tTG) and antiendomysium antibody (EMA) values. It is important to measure serum IgA level and IgG-tTG values should be considered in those with low IgA levels. In previous study, biopsyproven CD and positive EMA were reported in 60% of those with elevated IgA-tTG levels above the reference range, whereas biopsy-proven CD was reported in all patients with positive EMA [5]. European Society for Paediatric Gastroenterology, Hepatology and Nutrition working group suggested that typing for HLA-DQ2 and HLA-DQ8 can be helpful where there is uncertain diagnosis of CD; such as cases with negative CD antibodies and mild changes on biopsy or with strong clinical suspicion, highly specific CD antibodies and biopsies are not going to be performed, for example [4]. Monitoring for CD is required in children with unexplained poor growth, delayed puberty or unexplained gastrointestinal symptoms and screening in asymptomatic individuals who are at an increased risk is advised.

ESPGHAN 2012 Guidelines for Coeliac Disease Diagnosis: Validation Through a Retrospective Spanish Multicentric Study.

A large retrospective multicentre study was conducted in Spain to evaluate the efficiency of the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria for the diagnosis of coeliac disease (CD). The study protocol was approved by the ethics committee of Hospital Universitari i Politècnic La Fe (Valencia, Spain). The present study included 2177 children (ages 0.6-15.9 years) with small bowel biopsy (SBB) performed for diagnostic purposes (from 2000 to 2009) and with a minimum 2-year follow-up after biopsy. CD was diagnosed in 2126 patients (97.5%) and excluded in 51 (2.5%). Tissue transglutaminase antibodies (TG2A), anti-endomysial antibodies (EMA), and human leukocyte antigen (HLA) were reported in 751 patients, 640 symptomatic and 111 asymptomatic. TG2A levels >10 times the upper limit of normal, plus positive EMA and HLA DQ2 and/or DQ8 haplotypes, were found in 336 symptomatic patients, all of them with final diagnosis of CD. In 65 of 69 asymptomatic patients, 65 had confirmed CD and 4 did not have CD. According to the 2012 ESPGHAN guidelines, SBB may have been omitted in 52% of the symptomatic patients with CD with serologic and HLA available data. Gluten challenge was performed in 158 children, 75 of them <2 years at first biopsy. Only 1 patient in whom according to the new proposed diagnostic criteria gluten challenge would not have been mandatory did not relapse. Our results support the new ESPGHAN 2012 guidelines for diagnosis of CD can be safely used without the risk of overdiagnosis. A prospective multicentre study is needed to confirm our results.