Total Villous Atrophy Research Articles

New Onset Villous Atrophy in a Patient With Celiac Disease

New Onset Villous Atrophy in a Patient With Celiac Disease

Evidence Supporting Serology-based Pathway for Diagnosing Celiac Disease in Asymptomatic Children From High-risk Groups.

The European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines for diagnosing celiac disease (CD) in children were modified in 2012. They recommend that in symptomatic children with anti-tissue transglutaminase antibody (anti-tTG) titer of >10 times upper limit of normal (>10× ULN) and who have positive anti-endomysial antibody and HLA-DQ2/DQ8 haplotype, the diagnosis of CD can be based on serology. The aim of this study is to establish whether serology-based pathway of the ESPGHAN guidelines could also be reliably applied to asymptomatic children from high-risk groups. From March 2007 to February 2017, prospective data on anti-tTG titer, age, sex, and reason for screening were collected at diagnostic endoscopy on all asymptomatic children being diagnosed as having CD. The relationship between modified Marsh-Oberhuber classification histological grading and contemporaneous anti-tTG titers was analyzed. A total of 157 asymptomatic children were diagnosed as having CD. Eighty-four of 157 (53.5%) had antitTG >10× ULN (normal <10 IU/mL) and 75 of 84 were from high-risk groups. All 75 had definitive histological evidence (Marsh-Oberhuber 3a-3c) of small bowel enteropathy. Fifty-three of 84 children had anti-tTG >200 IU/mL and total villous atrophy was present in 29 of 53 (55%). Main reasons for serological screening were: type-1 diabetes mellitus (n = 36) and first-degree relatives with CD (n = 24). Mean age at diagnosis was 8.8 years. Serology-based diagnosis is cost-beneficial by around £1275 per child in the United Kingdom. All 75 asymptomatic children from high-risk groups with anti-tTG >10× ULN had histology-proven CD. This study provides further evidence that the guidelines for diagnosing CD by the serology-based pathway should be extended to these children.

Is celiac disease misdiagnosed in children with functional constipation?

Functional constipation is one of the common problems in childhood, and it comprises approximately 5% of the pediatric outpatient clinical applications. On the other hand, celiac disease (CD) is an immune enteropathy with the prevalence between 1/150 and 1/200. In addition to the classical symptoms of the disease such as diarrhea and weight loss, the incidence of atypical symptoms is increasing. This study aims to determine the prevalence of CD in patients with chronic constipation. The study was conducted between 2010 and 2012 and included 1046 children (range, 2-18 y; median, 11.4 y) diagnosed with chronic constipation according to the Rome III criteria. Serum immunoglobulin A, tissue transglutaminase, and/or anti-endomysial antibodies were examined. The patients with serological positive results were subjected to upper gastrointestinal system endoscopy and duodenal biopsy to confirm the diagnosis of CD. Blood tests were positive in 36 patients (3.25%). One of the patients had Hashimoto's thyroiditis, and 4 patients had short stature. Endoscopic findings included nodularity in bulbus and duodenal mucosa (n=16), scalloping fold (n=13), and normal mucosa (n=5). Histopathologic findings revealed that 10 patients had total villous atrophy, 24 patients had subtotal and partial villous atrophy, and 34 patients had intraepithelial lymphocyte infiltration. All patients followed a gluten-free diet, resulting in a resolution of symptoms. In the present study, a CD ratio of 1:28 was diagnosed in chronically constipated children. The use of screening tests for CD should be considered in children with conventional treatment-resistant constipation.

Histologic recovery among children with celiac disease on a gluten-free diet. A long-term follow-up single-center experience.

IntroductionCeliac disease (CD) is defined by gluten-induced immune-mediated enteropathy, affecting approximately 1% of the genetically predisposed population. The immunologic response to gluten causes characteristic intestinal alterations with gradual development. Histologic recovery of intestinal architecture was reported to occur within 6–12 months after starting a gluten-free diet, simultaneously with clinical remission. The aim of this study was to assess the rate and timing of histologic recovery among children with CD on a gluten-free diet, diagnosed and followed in an academic referral pediatric center during a 10-year period.Material and methods105 biopsy-confirmed CD children underwent follow-up small intestinal biopsies within at least 1 year after dietary gluten withdrawal. Further biopsies were performed if villous alterations were persistent. The Marsh classification modified by Oberhuber was used to score the histologic injuries. ResultsIn all 19 cases with Marsh type II at diagnosis, villous alterations normalized to Marsh type 0 within the first year. From 86 children enrolled with Marsh type III lesions, histologic remission was observed in 81.4% after 1 year, 91.8% within 2–3 years and 97.6% in long-term follow up (≥ 3 years). Two (2.3%) patients with concomitant selective IgA deficiency had symptoms of malabsorption and persisting villous atrophy lasting more than 3 years despite a gluten-free diet. There was a significant statistic difference between the proportion of children with Marsh type IIIA, type IIIB and Marsh type IIIC respectively that achieved histologic recovery within 1 to 2 years after gluten withdrawal. There were more children with partial 25 (92.6%) and subtotal villous atrophy 30 (88.2%) showing histologic improvement, compared to only 15 (60%) patients with total villous atrophy that recovered within the first 2 years of diet (p = 0.01 and p = 0.02 respectively).ConclusionsHistologic recovery in CD after starting a gluten-free diet in children takes at least 1 year and might be incomplete only in a small proportion of children, mainly associated with IgA immunodeficiency. Systematic follow-up of children with CD and persistent malabsorption syndrome is needed in order to avoid secondary complications.

English

The aim of the study is to evaluate paediatric patients with protein losing enteropathy (PLE). Fourteen cases diagnosed as PLE were evaluated in terms ofaetiologies, diagnostic methods, laboratory findings, treatment procedures and long-term prognosis. Four of the cases had coeliac disease, three intestinal lymphangiectasia, three giardia infection, one H pylori infection and three cytomegalovirus (CMV) infection. Histopathological examinations of duodenum specimens revealed total villous atrophy in four cases, lymphatic dilatation in three cases, severe nodular appearance in four cases and no pathology in four cases. All of the cases except patients with intestinal lymphangiectasia were controlled by the appropriate treatment given for the underlying disease. The cases with CMV infection were treated with only supportive treatment and gancyclovir therapy was not needed. When proteinuria is not detected in well-appearing children admitted with oedema, PLE must be considered.

English

This is a study to answer the question: Is there a relationship between occult celiac disease and functional dyspepsia? The study was carried out on 400 dyspeptic patients. Upper gastrointestinal tract (GIT) endoscopy was done for all patients and those with non-functional dyspepsia were excluded from the study. Duodenal biopsies with histopathological examination according to the Marsh-Oberhuber criteria were done. Serum tissue transglutaminase IgA antibody (anti-tTG-IgA) was done for patients with histopathological findings suggestive to have celiac disease (subtotal and total villous atrophy). 172 patients with endoscopic findings explaining their dyspeptic symptoms were excluded. Only patients with functional dyspepsia were enrolled in this study (228 patients). Bloating was the most common symptom (46.5%). Normal villous pattern was found in 199 cases (87.2%). Villous atrophy was found in 29 patients, subtotal atrophy in 20 cases (8.7%) and total atrophy in 9 cases (3.9%). Age group of 14-20 years (20/29, 90.9% patients) with villous atrophy was reported to have statistically significant difference (P value =0.000). Serum anti-tTG-IgA level was measured in all cases of abnormal villous pattern. Nine patients (3.9%) were proved to have a celiac disease (total villous atrophy and high serum anti-tTG-IgA) and fourteen dyspeptic patients (6.1%) had subtotal villous atrophy with high anti-tTG-IgA level could be diagnosed as occult celiac disease. Occult celiac disease should be suspected among patients with functional dyspepsia complaining of bloating, especially in age 14 to 20. Subtotal villous atrophy and high anti-tTG-IgA could be considered as occult celiac disease. Key words: Celiac disease, endoscopy, duodenal biopsy, functional dyspepsia.

Screening for coeliac disease in type 1 diabetes

In this issue of Acta Paediatrica, Laitinen et al. 1 explore symptoms and mucosal damage in 22 patients with type 1 diabetes who were screened for coeliac disease and compared them to 498 individuals diagnosed with coeliac disease on a clinical basis. The authors concluded that screening for coeliac disease should be considered among children with type 1 diabetes, which is in line with current recommendations 2-4. A meta-analysis found that coeliac disease occurred in more than one in 20 patients with type 1 diabetes 5, and long-term coeliac disease may influence the risk of both retinopathy and chronic renal disease in type 1 diabetes 6, 7, potentially due to an increased prevalence of microvascular complications in patients with both type 1 diabetes and coeliac disease 8. The paper by Laitinen et al. 1 is interesting for several reasons. First of all, the authors found that patients with type 1 diabetes and coeliac disease did differ from patients diagnosed with coeliac disease due to clinical symptoms. For instance, patients with type 1 diabetes and coeliac disease did not experience such poor growth as those with clinically diagnosed coeliac disease. That is reassuring, as poor growth in childhood can have long-term consequences. Although catch-up growth is commonly seen in children with coeliac disease just after diagnosis, restricting food intake to make a diet suitable for both type 1 diabetes and coeliac disease could theoretically make catch-up growth more difficult to achieve. The authors also found that while children with type 1 diabetes and coeliac disease often had unrecognised gluten-dependent symptoms, these were less severe than in children who were clinically diagnosed with coeliac disease. That was to be expected, because otherwise the children with type 1 diabetes and coeliac disease should have been diagnosed before, due to gastrointestinal symptoms, rather than just after their diagnosis of type 1 diabetes. We believe that the lower prevalence of symptoms reflects the fact that patients with type 1 diabetes and coeliac disease may have less severe small-bowel mucosal atrophy than patients who just have coeliac disease. We disagree with Laitinen et al. on their interpretation in this regard, as we believe that the lack of difference with regard to mucosal atrophy in their study was due to lack of power. Laitinen et al. based their findings on only 22 patients with type 1 diabetes and coeliac disease and the statistical lack of difference was probably due to the equal proportions of patients with subtotal villous atrophy. Estimating total villous atrophy from their Figure 1B seems to indicate that it was more common in patients with clinical suspicion of coeliac disease (roughly 23% versus 9%), while partial villous atrophy was more common in patients with type 1 diabetes (52% versus roughly 32%). The same objection could be raised about the conclusion that dietary adherence was similar in patients with both type 1 diabetes and coeliac disease and those with just coeliac disease. The power for dietary adherence was limited in type 1 diabetes and coeliac disease patients as there was only dietary data for 16 of the 22 patients, and the p value of 0.086 may have reached statistical significance if the type 1 diabetes and coeliac disease group had been larger. This said, it should be emphasised that a very high proportion of patients with type 1 diabetes and coeliac disease did comply with the diet. Nevertheless, the long-term implications of prescribing a life-long diet for a child based on screening are unknown, as adherence to a gluten-free diet may decline in adolescence among children with screen-detected coeliac disease. While the strongest evidence for the value of screening for coeliac disease would be derived from a randomised trial, in which a nonscreened group would be compared to a screened group with regard to morbidity, the length and expense of such a trial would probably be prohibitive. As such, we rely on observational studies, such as those by Laitinen et al., to inform us of the potential outcomes of screening. In conclusion, this article makes a valuable contribution to the literature and once again underlines the potential value of examining children with type 1 diabetes for other autoimmunity problems, including coeliac disease. None. None.

Coeliac disease associated with sarcoidosis and antiphospholipid syndrome: A case report

BackgroundSarcoidosis is a clinically heterogenous disease of unknown etiology with a hallmark of the development and accumulation of non-caseating granulomas in any organ. The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by an elevated risk for arterial and venous thrombosis and pregnancy-related morbidity. Celiac disease (CD) is a chronic, immune-mediated form of enteropathy that is now presenting later in life and often with extraintestinal manifestations. Co-existence of sarcoidosis, CD and APS is extremely rare. Case presentationWe describe a 27-year-old Tunisian woman with a history of non-explored superficial vein thrombosis and 4 successive miscarriages, who was explored for abdominal pain, vomiting, hypercalcemia, hepatic cytolyses and cholestasis and was complicated later with pancreatitis and anterior uveitis. Hepatic biopsy revealed noncaseating-granulomas, a high serum angiotensin converting enzyme activity was detected and the diagnosis of sarcoidosis was considered. A high titer of antiphopsholipid antibodies concluded the diagnosis of APS. Duodenal biopsies showed a total villous atrophy indicative of CD, confirmed by positivity of serum anti-endomisium and anti-transglutaminase antibodies. She had normocytic anemia (hemoglobin 9g/dl) and elevated transaminases. Thorough investigation established the diagnosis of extra pulmonary sarcoidosis associated with CD and APS. ConclusionCo-existence of sarcoidosis, CD and APS is extremely rare. APS should be recognized as an accompanying disorder of sarcoidosis and antiphospholipids measured especially when there is a history of thrombosis or miscarriages. CD should not be overlooked in association to sarcoidosis, given the shared immunological and genetic background, even in the absence of a typical presentation of the disease.

Anemia and Iron Deficiency in Children With Potential Celiac Disease.

Active screening for celiac disease frequently detects seropositive children with normal villous morphology (potential celiac disease). It remains unclear whether these subjects should be treated. We here investigated the prevalence of anemia and iron deficiency in children with potential and mucosal atrophy celiac disease. The prospective study involved 19 children with potential disease, 67 with partial or subtotal villous atrophy (P/SVA), and 16 with total villous atrophy (TVA). Twenty-three healthy children comprised the control group. The groups were compared for various clinical, histological, and laboratory parameters and hepcidin. The prevalence of abnormal parameters was as follows (controls, potential celiac disease, P/SVA, and TVA, respectively): anemia 0%, 15%, 22%, and 63%; low iron 5%, 0%, 14%, and 50%; increased transferrin receptor 1 5%, 16%, 20%, and 47%; low ferritin 0%, 21%, 35%, and 87%; and low transferrin saturation 10%, 11%, 41%, and 71%. One subject had low folate and none had low vitamin B12. The median values for hemoglobin, total iron, ferritin, and transferrin saturation were significantly lower and transferrin receptor 1 values higher in TVA group compared with other groups. After a median of 7 months on a gluten-free diet hemoglobin, total iron, ferritin, and albumin in children with P/SVA exceeded the baseline values in the potential celiac disease group. The development of anemia and iron deficiency in celiac disease is a continuum and may already be present in children with normal villous morphology, advocating an early diagnosis and possible dietary treatment of these patients.

Serebral kalsifikasyon tanısı alan hastalar çölyak hastalığı açısından araştırılmalı mı?

Objective: In this study, we aimed to examine the prevalence and relationship of celiac disease (CD) in children with cerebral calcifications (CC). Material and Methods: Children with cerebral calcifications were screened for celiac disease using the anti-tissue transglutaminase IgA antibody. Results: A total of 129 children with CC (75 boys, 54 girls; age: 6 months to 16 years) were evaluated. Control group consisted of 223 healthy children. The prevalence of CD was significantly higher in patients with CC than control subjects (p=0.01). In three patients pathological examination of duodenal biopsy resulted as total villous atrophy. All three patients had both iron deficiency anemia and short stature problem. Although, no calcification in occipital lobe was detected in computed tomography of these three patients, there were nonspecific calcifications in choroid plexus and pineal gland localizations. Conclusion: According to results from our study, prevalence of celiac disease being low in patients with intracerebral calcifications suggested that there is not a strong correlation between development of calcification and celiac disease. It suggested that occurrence of calcification in choroid plexus and/or pineal gland might be related to celiac disease.

The Prevalence Of Celiac Disease in Saudi Patients with Type 1 Diabetes Mellitus: Cross Sectional Study

Objectives: The relationship between type I diabetes mellitus (T1DM) and celiac disease (CD) has been known. The prevalence of CD in the Kingdom of Saudi Arabia (KSA) has not been determined. We examined the prevalence of celiac CD in patients in the Kingdom of Saudi Arabia with T1DM. Methods: A cross-sectional study for 218 patients with T1DM at the diabetic clinic of King Fahd Armed Force Hospital in Jeddah, KSA between January 2008 and June 2009. Anti-tissue transglutaminase antibodies (AntiTTG) was done in all patients. Duodenal biopsy were performed for patients with positive serology for Anti-TTG antibodies. Results: There were 69 males and 54 females who ranged in age from 12-50 years (mean ± SD 21.3 ± 7.2). The age at onset of type I diabetes mellitus was 13.8 ± 7.1 and the duration of type I diabetes mellitus was between 1 and 28 years (7.6 ± 5.7). Elevated Anti-TTG levels were found in the sera of 16 (7.3%) of 218 diabetic patients in our clinic. The gender ratio of the Anti-TTG positive is 1 male: 3 female. All None had any gastrointestinal symptoms. 12 of the 16 subjects had duodonal biopsies and 8 ( 3.7% ) biopsies showed total villous atrophy, 2 ( 0.8% ) subtotal villous atrophy and 2 ( 0.8 % ) chronic duodonitis , biopsy was not carried out in the other 4 subjects. Conclusion: The maximum prevalence of celiac disease in our population was 7.3% based on immunological marker and the minimum was 4.6% based on antibodies and biopsy results.

Endoscopic evaluation of celiac disease.

Although serology-based diagnosis of celiac disease (CD) in children recently has been legitimized 1, small bowel biopsy remains the gold standard for diagnosis of the condition 2 3. Upper endoscopy, therefore, takes on paramount importance in management of CD for several reasons, including serendipitous discovery of endoscopic markers of CD, assessment of “patchy” villous atrophy, targeting of biopsy sampling, and evaluation of CD-related complications. Macroscopic markers of CD, estimable with white light endoscopy, include the “scalloped” appearance of duodenal folds, nodular pattern of the mucosa (the so-called “mosaicism”), evidence of submucosal vessels, and epithelial fissurations 4. The diagnostic accuracy of these findings is largely variable, according to different reports 5 6, and they are associated with a significant rate of underdiagnosis of CD 7 8. Because standard endoscopy is unreliable, other endoscopic tools have been investigated for diagnosis opf CD, which fall into two categories based on their working principle: machine-independent techniques and machine-dependent techniques; the latter include software- and hardware-dependent techniques 9 10. The water-immersion technique (WIT) and dye-staining chromoendoscopy and machine-independent. Software-dependent techniques include Narrow-Band Imaging (optical dye-less chromoendoscopy), Fujinon Intelligent Chromo Endoscopy (virtual dye-less chromoendoscopy) and i-SCAN, which are dyeless chromoendoscopy tools. Hardware-dependent techniques such as optical coherence tomography, confocal laser endomicroscopy, video capsule endoscopy, and enteroscopy can be performed only with dedicated tools that are different from regular gastroscopes, or with the use of probes 9 10. The combination of these techniques has been suggested to improve the detection of duodenal villous abnormalities 11. In this issue of Endoscopy International Open, Iacucci et al 12 present a retrospective cohort study of 58 patients with clinical suspicion of CD and positive serology testings who underwent upper endoscopy and duodenal evaluation with both white light endoscopy (WLE) and a combination of i-SCAN and WIT (iSCAN-HDWI). The duodenal view was respectively classified as normal, reduction of folds, mosaic pattern, scalloping and atrophy with visible vessels with WLE, and as normal, mild, moderate, patchy or severe villous atrophy with iSCAN-HDWI. The authors found a significant correlation between the endoscopic grade evaluated by iSCAN-HDWI and the histology score. Assessment with WLE showed a lower but significant grade of correlation. In particular, iSCAN-HDWI achieved 96 % sensitivity, 63 % specificity, and 100 % accuracy for predicting duodenal damage (excluding Marsh I lesions), whereas WLE showed 78 % sensitivity, 50 % specificity, and 72 % accuracy for the same gold standard. Respectively, WLE identified no abnormalities in 55.6 % of patients diagnosed with patchy villous atrophy and in 33.3 % of patients diagnosed with mild villous atrophy after iSCAN-HDWI evaluation. WIT is an easy technique that allows real-time enhancement of duodenal villous pattern during upper endoscopy. After aspiration of air from the duodenal lumen, the operator injects 100 mL to 150 mL of water to highlight villi 13. WIT achieved high levels of accuracy in diagnosing total villous atrophy (TVA), with only slightly less accurate results in identifying partial villous atrophy (PVA) 14 15 16 17. i-SCAN is a digital tool developed by Pentax Medical. It enhances images through three different modalities: contrast enhancement, which highlights mucosal abnormalities, particularly those of depressed areas; surface enhancement, which increases contrast between light and dark; and tone enhancement, which groups and recombines blue, red, and green components of images. i-SCAN produced results similar to WIT in assessment of TVA and PVA 18. The combination of iSCAN technology with WIT both highlights vascular and mucosal pattern and allows direct visualization of villi. Such a “joint-venture” can be of help in evaluating the duodenal villous pattern, especially in the case of partial or patchy villous atrophy, and in targeting biopsy sampling; therefore, it is advocated to decrease the number of CD misdiagnoses and related unnecessary costs. Further studies, combining other modalities for imaging enhancement, are therefore welcome to improve our knowledge of the diagnostic potential of endoscopic tools in CD.

Celiac disease in children with chronic constipation.

Chronic constipation (CC) and celiac disease (CD) are the most common conditions encountered in pediatric gastroenterology. The association of these two disorders has not been evaluated properly. We analyzed the prevalence and outcome of CD in children with CC. The study included children with CC (n = 313) and healthy children (n = 990). Serum IgA and IgA antitissue transglutaminase antibodies (IgA-tTG) were studied in all subjects. Intestinal biopsy and HLA-DQ2/DQ8 typing was performed in subjects with elevated IgA-tTG. Serology was positive in 8 children (2.5%) with CC and 6 children (0.6%) from the control group (P < 0.05). Histopathological examination revealed total villous atrophy in two subjects in the control group. Other subjects had Marsh 0-1 lesions. All patients with CC and 4 children from the control group were classified as having potential CD. Two children in the control group had silent CD. Spontaneous loss of serum tTG-IgA occured in 75% of the subjects with potential CD at the end of the 1st year. Our study revealed that serological evaluation CD may be omitted in children with CC at initial examination. It may be perform in selected patients such as those associated with prolonged symptoms or malnutrition.

Factors associated with growth disturbance at celiac disease diagnosis in children: a retrospective cohort study.

BackgroundImpaired growth is a well-known complication in celiac disease, but factors associated with it are poorly known. We investigated this issue in a large cohort of children.Methods530 children with biopsy-proven celiac disease were included. The participants were divided into two groups on the basis of the presence (n = 182) or absence (n = 348) of growth disturbance at diagnosis. Histological, serological and clinical characteristics were compared between children with growth failure and those with normal growth. Further, patients with growth failure as the sole clinical presentation were compared to those with poor growth and concomitant other symptoms.ResultsChildren with growth failure were younger (p < 0.001) and had lower hemoglobin (p = 0.016) and higher celiac antibody (p < 0.001), alanine aminotransferase (p = 0.035) and thyroid-stimulating hormone values (p = 0.013) than those with normal growth. Significantly associated with growth failure at diagnosis were age <3 years (OR 4.3 (95 % CI 2.5-7.5) vs older age), diagnosis before the year 2000 and in 2000–09 (OR 3.1 (1.8-5.4) and OR 1.8 (1.1-2.8) vs diagnosis in 2010–2013), presence of total and subtotal villous atrophy (OR 4.2 (2.5-7.0) and OR 2.0 (1.3-3.2) vs partial atrophy), severe symptoms (OR 3.4 (1.8-6.7) vs mild symptoms) and vomiting (OR 3.1 (1.5-6.3). The presence of abdominal pain reduced the risk (OR 0.5 (0.3-0.7)), while there was no effect of gender, diarrhea, constipation, other chronic diseases and celiac disease in the family. Children evincing poor growth as the sole clinical presentation were older (p < 0.001) and had higher hemoglobin (P < 0.001) and total iron (p = 0.010) values and lower TG2ab values (p = 0.009) than those with growth disturbance and other symptoms.ConclusionsIn particular young age and severe clinical and histological presentation were associated with growth disturbance at celiac disease diagnosis. Children with only poor growth are markedly different from those with other concomitant symptoms, suggesting different pathogenic mechanisms.

A Case of Heart Failure and Diarrhea

A 20 year-old-man with no significant past medical history was admitted with a 5 day history of intermittent chest pain and dyspnea. He also reported a 3 month history of diarrhea with multiple, loose, watery, non-bloody bowel movements daily. He denied recent travel, antibiotic use, medication changes, illicit drug use, or significant alcohol consumption. Physical examination was notable for tachycardia and III/VI apical systolic murmur. Laboratory evaluation was pertinent for hemoglobin 10 g/dL with an MCV of 75.5 fL, NT-proBNP of 18,995 pg/mL, INR of 2.3, albumin of 2.5 g/dL, C-reactive protein of 91.3 mg/L, AST of 66 u/L, ALT of 62 u/L, IgA level of < 1 mg/dL, tissue transglutaminase IgG level > 100 u/mL and anti-gliadin IgG level was 90.5 U. Total levels of IgG and IgM were normal. Upper endoscopy demonstrated a scalloped and mosaic pattern mucosa in the duodenum and biopsies showed total villous atrophy, increased intraepithelial lymphocytes, and crypt hyperplasia consistent with celiac disease. He was started on gluten-free diet with rapid resolution of diarrhea. Transthoracic echocardiogram was notable for an ejection fraction of 21%, severe generalized global hypokinesis and mildly dilated left ventricle. Cardiac MRI demonstrated endocardial delayed enhancement of the left ventricular wall concerning for infarction of the circumflex territory. Coronary angiography demonstrated normal coronary arteries. Right ventricular biopsy showed moderate lymphocytic myocarditis. Patient was initiated on furosemide, metoprolol, lisinopril and discharged from the hospital. He had follow-up echocardiogram one month later. This showed an ejection fraction of 23% and incidental finding of left ventricular apical thrombus. He was initiated on warfarin therapy. One month later, he was admitted with worsening dyspnea, lower extremity edema, and 10 pound weight gain. Echocardiogram demonstrated an ejection fraction of 11%. He maintained strict adherence to a gluten-free diet. He was initiated on immunosuppression with azathioprine 100 mg and prednisone 60 mg with a 4 month taper. He had progressive improvement in fluid retention and resolution of dyspnea. Follow-up echocardiogram one month later demonstrated improved ejection fraction of 34%. This case highlights the association of autoimmune myocarditis with celiac disease. If cardiac function does not improve with a gluten-free diet alone then immunosuppression should be initiated.

G80(P) The relationship between tissue transglutaminase antibody titres and histological classification in celiac disease

BackgroundCoeliac disease (CD) is an immune mediated systemic disorder elicited by the ingestion of gluten and related prolamines in genetically susceptible individuals. Diagnosis has been based on small bowel histology...

The Challenging Diagnosis of Cronkhite-Canada Syndrome in the Upper Gastrointestinal Tract

Cronkhite-Canada syndrome is a rare protein-losing enteropathy, classically characterized by ectodermal changes and gastrointestinal polyposis. The etiology remains obscure but immune dysregulation may be important. The diagnosis of Cronkhite-Canada syndrome in the upper gastrointestinal tract is challenging, frequently resulting in delayed patient management. In this study, we described the initial clinical presentations, upper gastrointestinal endoscopic appearances, clinical follow-up, and histologic diagnoses in 7 patients who were subsequently diagnosed with Cronkhite-Canada syndrome. Histology slides were reviewed, and IgG4 immunohistochemical analysis was performed. The most common initial endoscopic impressions were antral malignancy and gastric infection, but gastroduodenal polyposis was not described. On histologic review, the main findings in the gastric mucosa were a prominent mucosal edema, a mixed inflammatory infiltrate rich in eosinophils, and architectural changes with gland dilatation and withering. In the duodenal mucosa, total or subtotal duodenal villous atrophy, inflammation, crypt distortion, and increased apoptotic bodies were the most common features. Three patients died of the disease, and 4 patients were asymptomatic at a mean follow-up of 3.5 years. No intestinal malignancy had been diagnosed. In 2 patients foci of dysplasia in colonic polyps were identified. In only 1 patient, a significant increase in IgG4-positive plasma cells was observed in a colonic polyp. In summary, we found that patients with Cronkhite-Canada syndrome have histologic features commonly found in other immune disorders of the gastrointestinal tract that may help in establishing the diagnosis and further supports the hypothesis that Cronkhite-Canada syndrome may represent an immune dysregulation syndrome, different from IgG4-related disease.

Congenital Microvillous Atrophy, Report of Two Consecutive Siblings with Complete Histologic, Immunohistochemical and Detailed Electron Microscopic Studies, First Report from Iran

Introduction: Microvillous inclusion disease (MVD) or microvillous atrophy disorder is a congenital disorder of the small intestinal epithelial cells that presents with persistent and severe diarrhea and it is characterized by enterocytes abnormalities [1] 08D0C9EA79F9BACE118C8200AA004BA90B02000000080000000005F005200650066003300380035003800380033003700360030000000 . For these children, prognosis is generally poor due to metabolic acidosis with poor compensation. To our experiment, this disease is very rare in Iran and it is yet unreported, so we decided to report two consecutive siblings with the same disease from Iran. Report of Cases: Two siblings were born to healthy parents. Parents were cousins. Both siblings were hospitalized due to severe diarrhea starting shortly after breast feeding. The frequency of diarrhea in both cases was 10 to 17 times per day and their stools were loose and green. Histological studies of both siblings revealed duodenal mucosa with complete flattening of villi (total villous atrophy). Superficial lining cells showed atrophy. Crypts showed no hyperplasia, however it showed distortion and difference in size. By PAS staining and CD10 staining, a poorly developed brush border and typical inclusions were seen in apical boarder of enterocytes. Electron microscopy was performed for the second case and showed microvillous involution and inclusions in the apical part of the epithelial cells. Discussion: Microvillous congenital atrophy is a rare congenital disorder. Due to rareness of congenital microvillous atrophy (CMA), it is crucial to distinguish it from other diseases with persistent and severe diarrhea as soon as possible.

O PRINCÍPIO DO DIREITO HUMANO À ALIMENTAÇÃO ADEQUADA E A DOENÇA CELÍACA: AVANÇOS E DESAFIOS

Celiac disease is characterized by partial or total intestinal villous atrophy, caused by gluten ingestion in wheat, rye, barley, malt and oats. In the general population, the prevalence average is about 1%. The recommended nutritional therapy is the complete removal of gluten from the diet, since this causes the symptoms regress and nutritional status is restored. This paper seeks to contextualize the food and nutrition insecurity that afflicts individuals with celiac disease, specifically with regard to the principle of the Human Right to Adequate Food (HRAF). This, in turn, establishes as a fundamental human right to food availability in quantity and quality and also values welfare, promoting the health of the entire population. However, the limited availability of products intended for celiac individuals in the market, the high cost and the gluten contamination, contribute to a constant situation of food and nutritional insecurity to holders of this special dietary need. Diet is the single most secure treatment form for this disease, enabling its control. It can be said, therefore, that the public needs actions, or even public policies to materialize this right, thus ensuring access to adequate food to this population.

Su1019 Mucosal Healing and Risk of Lymphoproliferative Malignancy in Celiac Disease

Background: Celiac disease (CD) is associated with an increased risk of lymphoproliferative malignancy (LPM). It is unknown whether this risk is affected by the results of the followup intestinal biopsy, performed to document mucosal healing. We aimed to quantify the risk of LPM in those patients with CD who had persistent villous atrophy and those patients who had mucosal healing on follow-up biopsy. Methods: Using a population-based database that included all pathology departments in Sweden (n=28), we identified all patients with CD (equal to villous atrophy, Marsh histopathology stage 3) who had a follow-up biopsy between six months and five years after initial diagnosis, and compared the risk of LPM to that of the general population using expected rates based on age, gender, and calendar year. We used Cox regression to compare the rate of LPM in those with persistent villous atrophy to those with mucosal healing. Results: Among 7,625 patients with CD and a follow-up biopsy, persistent villous atrophy was present in 3,308 (43%). LPM developed in 53 (0.7%) patients, with a median time to LPM of 4.9 years after follow-up biopsy. The overall risk of LPM was increased compared to the general population (Standardized incidence ratio, SIR 2.81; 95% CI 2.10-3.67), but this increase was limited to those with persistent villous atrophy (SIR 3.78; 95% CI 2.71-5.12) with no significant increased risk among those with mucosal healing (SIR 1.50; 95% CI 0.77-2.62). Persistent villous atrophy compared to mucosal healing was associated with an increased risk of LPM (Hazard ratio, HR 2.26; 95% CI 1.18-4.34). This risk was primarily observed for T cell lymphoma (HR 3.51; 95% CI 0.75-16.34), with no association for B cell lymphoma (HR 0.97; 95% CI 0.21-4.49). Patients with subtotal or total villous atrophy on follow-up biopsy had a greater increase in LPM risk (HR 3.96; 95% 1.65-9.50) compared to those with partial villous atrophy (HR 1.90; 95% CI 0.70-5.19). Conclusions: The increased risk of LPM in CD is markedly influenced by the results of the follow-up biopsy; those with mucosal healing have an LPM risk similar to that of the general population. The increased risk of LPM among those with persistent villous atrophy is mainly for T cell lymphoma. Follow-up biopsy can effectively stratify CD patients regarding subsequent LPM risk.