Total Villous Atrophy Research Articles

Celiac disease in Tunisian children: A second screening study using a “new generation” rapid test

This work aims to estimate celiac disease prevalence in school-children in the island of Djerba and assess rapid method feasibility for screening. We screened 2064 schoolchildren by a rapid method to detect IgA anti-tissue transglutaminase and IgA deficiency. Children with positive results were tested for IgA anti-transglutaminase and anti-endomysium by conventional tests. In positive children, intestinal biopsy was performed. IgA deficiency suspected by rapid method was confirmed by nephelometry. In these cases IgG anti-endomysium was performed. Rapid test was positive in 7 children; conventional serology was positive in all and 6 of them accepted the biopsy. Total villous atrophy was observed in 5 while intestinal mucosa was normal in one. Among children with positive serology, 3 had silent form, 1 chronic diarrhea, one growth failure and 2 had borderline growth. IgA deficiency was suspected in 13 cases and was confirmed in 11 children tested. Prevalence of celiac disease was 0.24–0.34% and that of IgA deficiency 0.5–0.6%. This screening study confirms that celiac disease is relatively common in schoolchildren in Tunisia. It confirms also that even those with symptoms typical for celiac disease escape diagnosis. Rapid test is better accepted by parents and children than test requiring a venous blood sample.

Diagnosis of Coeliac Disease in Children Younger Than 2 Years

To diagnose coeliac disease (CD) in children younger than 2 years, the old ESPGHAN criteria based on 3 small bowel biopsies were recommended until recently. The aim of the present study was to investigate the applicability of only 1 small intestinal biopsy plus positive serology for the diagnosis of CD in children younger than 2 years. A prospective cohort study included 81 patients younger than 2 years with symptoms suggestive of CD, who all completed the diagnostic procedure based on 3 small bowel biopsies. According to the finding of the third biopsy, patients were divided into group A-CD confirmed (N = 44), and group B-CD not confirmed, after the gluten challenge (N = 37). At the time of the first biopsy, total villous atrophy (Marsh IIIc) was found more often in group A than in group B (77% vs 27%, P < 0.01). Also, all of the studied antibodies were more frequently positive in group A than in group B (P < 0.01 for all of the tested antibodies). Positive anti-endomysial antibodies and Marsh IIIc finding were the best discriminators between the group A and the group B and considerably contributed to the prediction of CD. The second and the third biopsies (before and after the gluten challenge) may also be avoided when diagnosing CD in children younger than 2 years provided that the child, at the time of presentation, has positive anti-endomysial antibodies and Marsh IIIc on the small bowel biopsy. A gluten challenge should be still considered in all other children younger than 2 years.

Consumption of gluten with gluten-degrading enzyme by celiac patients: A pilot-study

To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease (AN-PEP) to mitigate the immunogenic effects of gluten in celiac patients. Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet (GFD) resulting in normalised antibodies and mucosal healing classified as Marsh 0 or I were included. In a randomised double-blind placebo-controlled pilot study, patients consumed toast (approximately 7 g/d gluten) with AN-PEP for 2 wk (safety phase). After a 2-wk washout period with adherence of the usual GFD, 14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk (efficacy phase). Measurements at baseline included complaints, quality-of-life, serum antibodies, immunophenotyping of T-cells and duodenal mucosa immunohistology. Furthermore, serum and quality of life questionnaires were collected during and after the safety, washout and efficacy phase. Duodenal biopsies were collected after the safety phase and after the efficacy phase. A change in histological evaluation according to the modified Marsh classification was the primary endpoint. In total, 16 adults were enrolled in the study. No serious adverse events occurred during the trial and no patients withdrew during the trial. The mean score for the gastrointestinal subcategory of the celiac disease quality (CDQ) was relatively high throughout the study, indicating that AN-PEP was well tolerated. In the efficacy phase, the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed. During the efficacy phase, neither the placebo nor the AN-PEP group developed significant antibody titers. The IgA-EM concentrations remained negative in both groups. Two patients were excluded from entering the efficacy phase as their mucosa showed an increase of two Marsh steps after the safety phase, yet with undetectable serum antibodies, while 14 patients were considered histologically stable on gluten with AN-PEP. Also after the efficacy phase, no significant deterioration was observed regarding immunohistological and flow cytometric evaluation in the group consuming placebo compared to the group receiving AN-PEP. Furthermore, IgA-tTG deposit staining increased after 2 wk of gluten compared to baseline in four out of seven patients on placebo. In the seven patients receiving AN-PEP, one patient showed increased and one showed decreased IgA-tTG deposits. AN-PEP appears to be well tolerated. However, the primary endpoint was not met due to lack of clinical deterioration upon placebo, impeding an effect of AN-PEP.

Celiac disease prevalence in children and adolescents with myocarditis and dilated cardiomiopathy

To determine the prevalence of celiac disease in patients with myocarditis and dilated cardiomyopathy. Fifty-six patients between 1 and 18 years old with dilated cardiomyopathy or myocarditis were evaluated and followed up at Instituto de Medicina Integral Professor Fernando Figueira. Patients with previous diagnosis of celiac disease were excluded. The functional classification was determined according to the American Heart Association criteria (classes I, II, III and IV). Diagnosis of myocarditis was reported in the patients' medical records. Dilated cardiomyopathy was diagnosed by echocardiogram with systolic dysfunction of one or both ventricles, ejection fraction lower than 55%, ventricular dilatation, and left ventricular diastolic diameter bigger than 112%. Patients answered a questionnaire about gastrointestinal and cardiac symptoms; next, anti-tissue transglutaminase (tTG) and anti-endomysial (EMA) antibodies were dosed. Those with positive antibody results were referred to intestinal biopsy and histological evaluation to detect celiac disease according to Marsh classification. One of the 56 children (1.8%) had positive tTG antibody level, but negative EMA. Intestinal histological evaluation showed total villous atrophy. Approximately, 30% of patients had heart failure. Gastrointestinal symptoms and signs were frequent, especially abdominal pain (70%, 39/56). Celiac disease prevalence in pediatric patients with dilated cardiomyopathy or myocarditis was 1.8%. It is important to investigate celiac disease in patients with these conditions to avoid the progression of such diseases and patients' clinical deterioration.

An Unusual Cause of Chronic Diarrhea

Case: 79-year-old Caucasian woman with diabetes and chronic bronchiectasis was admitted with nine months of refractory nausea, vomiting and diarrhea, and associated weight loss. Had large volume stools with nocturnal symptoms, without blood or mucus. There was no coincident travel or new medications. Nasojejunal feeds were initiated for intractable emesis. Labs showed anemia with elevated ESR and CRP. She also had low albumin, hypovitaminosis D, and coagulopathy. Stool studies were negative for infection or inflammation. Fecal elastase was undetectable, with stool osmolar gap suggestive of osmotic diarrhea. Qualitative fecal fat was normal. Upper and lower endoscopy revealed multiple discrete ulcers in the proximal colon, otherwise unremarkable. Duodenal biopsies revealed total villous atrophy and extensive subepithelial collagen deposits on trichrome stain, with denuded surface epithelium, consistent with collagenous sprue. There was no increase in intraepithelial lymphocytes. Histology of colonic ulcers noted focal areas of fibrosis that did not meet criteria for collagenous colitis. Celiac serology was negative for anti-TTG and anti-endomysial antibodies with low IgG and IgA levels; genotyping for HLA-DQ2 was positive. Testing for anti-enterocyte antibodies was negative. The patient was started on a gluten free diet (GFD), pancreatic enzymes and systemic steroids. She noted decreased stool frequency and tolerance of oral diet by day 3, and was discharged on prednisone taper. At one month, she was in clinical remission, and steroids were discontinued. Three months after diagnosis, she remains asymptomatic on GFD and pancreatic enzymes, with improvement of nutritional lab markers. Discussion: Collagenous sprue (CS) is a rare condition, originally described as a refractory form of celiac disease (CD). It is now considered more heterogeneous, with links to CVID or as a paraneoplastic syndrome. Our patient did not have positive CD serology. Low initial immunoglobulin levels normalized with clinical remission. CS presents with chronic diarrhea, malabsorption and weight loss. Diagnosis is established on intestinal biopsy with a subepithelial collagen layer greater than 10 mu and inflammatory cells in the lamina propria. Evaluation for coexisting microscopic colitis should be performed. Diarrhea is classically unremitting without aggressive immunosuppression. Steroids are the mainstay of therapy along with GFD, with remission rates of up to 80%. However, the clinical course is unpredictable and often poorly responsive to medical therapy. Early recognition of CS is essential to prevent significant morbidity and mortality. However, more data are needed to optimize therapeutic strategies.

Salivary Ceruloplasmin Ferroxidase &amp; Oxidase Activities in Celiac Patients

The aim of the current study was to evaluate salivary ferroxidase ceruloplasmin activities in celiac patients with different histopathological severity. This study included 75 celiac patients with different mean age (18.68 ± 11.13) year, who had positive screen for celiac antibodies, and who had gastrointestinal symptoms. In order to simplify the comparison with the healthy control group, celiac patients were divided into two groups according to their histopathological severity: severe (marsh IIIa, b, c) &amp; less severe (marsh 0, I). All these patients have been evaluating for salivary ceruloplasmin (Cp) concentration and Cp ferroxidase activities. To confirm the presence of the enzymatic activity of this protein, polyacrylamide gel electrophoresis was carried out and then stained for Cp ferroxidase, as well as for Cp oxidase activity. Furthermore, the concentrations of salivary total protein, albumin, and globulin were measured in the studied groups. A significant increase (p&lt;0.05) in salivary concentration of ceruloplasmin was found in all above mentioned patients groups in comparison to that of the control group, except for total villous atrophy (marsh IIIc) patients subgroup. Salivary Cp ferroxidase activity revealed statistically significant decrease among the patient groups as well as between them and the control group. The result of salivary total protein and globulin showed presence a significant increase (p&lt;0.05) in comparison to that of the control group. Meanwhile albumin levels was found to increase non-significantly (p=0.186).

Age-Related Patterns in Clinical Presentations and Gluten-Related Issues Among Children and Adolescents With Celiac Disease

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

Gluten and dyspepsia.

Celiac disease (CD) affects approximately 1% of the population. It is a disease that causes flattening of the epithelial lining of the small bowel and is characterized by (sub) total villous atrophy. The histological alterations in CD are graded according to the modified Marsh Classification from Marsch 0 (normal mucosa) to Marsch IIIc (total villous atrophy). Common symptoms include, but are not restricted to, malasborption, diarrhoea, malnutrition, failure to thrive in children and abdominal pain. Some patients with CD have no gastrointestinal symptoms or are asymptomatic (1). CD is caused by intolerance to gluten and a strict gluten free diet is the only available treatment. In the lamina propria of the small intestine of patients with CD there are T cells that respond to gluten fragments bound to the disease predisposing HLA-DQ2 and/or HLA-DQ8 molecules and secrete proinflammatory cytokines. The diagnosis of CD is based on the combination of HLA typing for DQ2 and DQ8, serum determination of specific CD antibodies (IgA anti-transglutaminase (tTG) and IgA antiendomisium (EMA) antibodies), on the results of small bowel biopsies and on the improvement of the symptoms after adherence to a gluten free diet (1–3). In this number of GHFBB, Rostami Nejad and co-authors report on the prevalence of CD in patients with dyspepsia and on the value of histology of the small bowel and of determination of specific CD antibodies in the diagnosis of CD in these patients (4). To study this, the authors performed small bowel biopsies and determined total IgA and IgA tTG (or IgG in case of IgA deficiency) in 407 randomly chosen adult patients who underwent diagnostic upper gastrointestinal endoscopy for dyspeptic symptoms. CD was identified by histological alterations characteristic of gluten sensitive enteropathy and by consistent CD serology. Biopsy results were classified as absence of CD (Marsh 0) or suggestive of CD (Marsh I to IIIc). There were 26 (6.4%) cases with enteropathy, among them 12 cases with Marsh I and 4 with Marsh II. Thirty three (8.1%) of the patients had tTGA level more than 15 u/ml, considered as tTGA positive, 10 of them (2.5%) had abnormal histology (Marsh I,-IIIc), including 5 patients with Marsh IIIa-c (1.3%). This last figure is in line with frequencies of CD previously reported among patients with dyspepsia (5–7). The authors discuss if the real frequency of CD in dyspepsia should be considered as high as 8%, as assessed by determination of specific CD antibodies, since they have been shown to perform better than histology in the diagnosis of CD (8). Some strong points of the study of Rostami Nejad and co-authors are, among others, its prospective design, the randomly inclusion of the 407 patients with dyspepsia who underwent upper gastrointestinal endoscopy during the study and the completeness of the total IgA and tTG results in their patients. However, the study has also shortcomings. The authors considered levels higher than 15 U/ml as tTGA positivity. This level possibly represents the cut-off of normality of the tTGA determination in serum in their laboratory. However, it is known that lower levels of tTGA are less indicative for CD than higher levels, and that in CD there is a correlation between the TGA levels and the degree of small bowel damage. So, it should have been useful if the authors had presented the data on the correlation between the tTGA levels and the Marsch classifications of their patients. This is especially important in the cases with Marsch I alterations, since in absence of specific CD antibodies, these lesions are almost never indicative of CD (7). In addition, it is also known that “false positive” levels of tTGA are almost always present at low levels and in absence of EMA. So, the addition of EMA determinations, especially in these patients with elevated tTGA, should have added strength to the study. The authors rightly state that there is no a single perfect test to diagnose CD in its own. One additional, but important, part of the diagnosis is the improvement of the symptoms after the start of a gluten free diet. In this contest, information over the improvement of the symptoms of dyspepsia in the studied patients after adherence to the diet should be important, especially if, as the authors suggest, CD screening should be done in all patients with these symptoms.

Son Dönem Böbrek Yetmezliğine İlerleyen Fokal Segmental Glomerülosklerozlu Bir Çölyak Hastalığı Olgusu

In this case report a 5-year-old girl is presented who had Celiac disease and presented with nephrotic syndrome due to focal segmental glomerulosclerosis. Her intestinal biopsy which had been performed 2 years previously had revealed chronic duodenitis characterized by total villous atrophy and crypt hyperplasia. She presented with abdominal cramps, diarrhea, nausea, vomiting, failure to thrive and generalized edema while she was on gluten-free diet and in clinical remission for the disease. Kidney biopsy was performed considering the probable diagnoses of nephrotic syndrome and renal failure. The histopathological diagnosis was a cellular type focal segmentary glomerulosclerosis. A progressive deterioration could not be prevented in renal functions despite all therapeutic approaches including pulse methylprednisolone and cyclophosphamide administration. An end-stage renal disease (ESRD) developed within eight months, and the patient died due to the cardiovascular complications of ESRD 18 months after the initial presentation of renal findings. Very rare association of progressive glomerular disease and Celiac disease should be kept in mind during the follow-up of any child with Celiac disease

Coeliac disease: changing diagnostic criteria?

Coeliac disease: changing diagnostic criteria?

Have serological tests changed the face of childhood coeliac disease? A retrospective cohort study

ObjectivesThe aim of this study was to evaluate if the use of antitransglutaminase (tTG) and antiendomysium (EM) antibodies has modified the profile of coeliac disease (CD) in children.DesignRetrospective cohort study.SettingMonocentric...

Duodenal Ulceration in a Patient With Celiac Disease and Plasminogen I Deficiency: Coincidence or Cofactors?

Celiac disease (CD) is a gluten-dependent inflammatory disease of the small bowel that affects up to 1% of the worldwide population. Despite severe mucosal abnormalities including total villous atrophy and autoantibody deposition, duodenal ulcer is not a feature of CD. However, a recent study found an elevated rate of peptic ulcer disease in patients with CD. Plasminogen deficiency (PLD) is an autosomal recessive disease that causes pseudomembranous lesions in different organs, but gastrointestinal involvement is rare. Here we report the case of a 6-year-old girl who had a sudden onset of hematemesis caused by duodenal ulcer. On the basis of mucosal atrophy, elevated celiac antibody levels, decreased plasminogen serum activity, and homozygous missense mutation R216H in the plasminogen gene, CD and PLD were diagnosed. This report is, to our knowledge, the first description of the 2 entities, and results of our double-immunofluorescent studies also suggest that both diseases may have a role in the ulceration process. Excessive amounts of fibrin deposition due to PLD caused the distortion of the vessels and was responsible for the unusual celiac immunoglobulin A and tissue transglutaminase 2 in vivo binding pattern. On the basis of this result, patients with CD and unknown cause of gastrointestinal ulcer may require investigation for PLD.

A Child With Refractory Coeliac Disease

A Child With Refractory Coeliac Disease

Lysozyme-rich mucus metaplasia in duodenal crypts supersedes Paneth cells in celiac disease

Lysozyme is as an innate enzyme with potent antibacterial properties found in Paneth cells in normal duodenal crypts. Since celiac disease concurs with an abnormal duodenal microbiota we explored the expression of lysozyme in this disease. Fifty-three duodenal biopsies were stained with anti-lysozyme: 15 had normal duodenal mucosa (NDM), 7 chronic active duodenitis (CAD), 3 borderline (BL), 17 subtotal villous atrophy (SVA) and 11 total villous atrophy (TVA). NDM showed lysozyme-positive Paneth cells arranged in "Indian file" in 93.3%. In contrast, lysozyme-positive mucus metaplasia in crypts (LPMMC) replacing Paneth cells was found in 71.5% in CAD, in 96.4% in SVA/TVA, and in 2 cases with B. In 19.3% cases with BL/SVA/TVA, LPMMC replaced all Paneth cells in all crypts in entire sections. In crypts and villi, lysozyme-positive goblet cells (LPGC) were found in 92.8%. Changes were more frequent in the duodenal bulb than in pars descendens. In normal duodenal mucosa, absorptive enterocytes and goblet cells migrate from stem cells upwards, while Paneth cells migrate downwards, towards the base of the crypts. In celiac disease stem cells seem to have been re-programmed, as the normal production of Paneth cells in the crypts was replaced by lysozyme-producing mucus cells. LPMMC and LPGC in celiac disease might mirror an antimicrobial adaptation of stem cells to signals generated by pathogenic duodenal bacteria. The molecular mechanism(s) behind the abrogation of Paneth cells in duodenal crypts and its substitution by LPMMC in celiac disease remains to be elucidated.

Mean platelet volume could be a promising biomarker to monitor dietary compliance in celiac disease

Background. Celiac disease (CD) is an autoimmune disease that develops in patients with a genetic predisposition, incurring a susceptibility to gluten-containing foods such as barley, wheat, and rye. The elimination of gluten from the diet is the main therapeutic approach and usually leads to clinical and laboratory improvement. There are no ideal markers that objectively assess dietary compliance in CD patients.Materials and methods. Sixty newly diagnosed CD patients (male/female: 43/17) and 40 healthy subjects (male/female: 23/17) were enrolled in this study. The diagnosis of CD was established by both histological findings of duodenum biopsy (total villous atrophy and lymphocytic infiltration) and positive antibodies against endomysium or gliadin.Results. A significantly higher mean platelet volume (MPV) was observed in the CD group compared with healthy subjects (8.45 ± 0.96 fL versus 7.93 ± 0.63 fL; p = 0.004). After introduction of a gluten-free diet, the MPV of CD patients in the dietary adherent group was significantly lower than that of the non-adherent group (8.09 ± 0.6 fL versus 8.9 ± 1.08 fL; p = 0.001). Overall dietary adherence rate was 71.6% (43/60 CD patients). In the dietary compliant group, initiation of gluten-free diet was associated with a significant decrease in MPV from base-line values (8.56 fL versus 8.25 fL; p = 0.008). In the non-adherent group, MPV on 3-month follow-up was higher than at base-line (8.05 fL versus 8.91 fL; p = 0.001).Conclusion. MPV could be a promising and easily available biomarker for monitoring of dietary adherence in CD patients at a low cost in comparison with other modalities.

HLA‐DQ Genotyping Combined With Serological Markers for the Diagnosis of Celiac Disease: Is Intestinal Biopsy Still Mandatory?

The aim of this study was to evaluate the value of HLA-DQ2/DQ8 allelic genotyping combined with serologic testing for the diagnosis of celiac disease (CD). One hundred seventy children, who underwent jejunal biopsy for digestive symptoms or malnutrition, were tested for HLA-DQ2/DQ8 and serologic markers (tTG and/or anti-endomysial antibodies). Children were classified in 2 groups, according to jejunal histology: group 1, when partial or total villous atrophy was associated with an increased intraepithelial lymphocytosis suggesting CD, and group 2, when these histological criteria were absent. Eight children were excluded from the study because their intestinal histology was not informative; 82 children were classified in group 1 and 80 in group 2. Eighty-one of 82 children in group 1 were positive for HLA and serologic testing. The other child had negative HLA and serologic testing but marked villous atrophy, and further investigation showed an allergic disease. Among the 80 children in group 2, 53 were negative for both HLA and serologic testing, 22 were positive for HLA but negative for serologic testing, 2 were negative for HLA and positive for serologic testing, and 3 patients were positive for both HLA and serologic testing. The last 3 children were shown to have an autoimmune background and had probably a latent form of CD. The association of HLA-DQ2/DQ8 and serologic markers had a sensitivity of 98.8%, a specificity of 96.2%, a positive likelihood ratio of 26.3, and a negative likelihood ratio of 0.013. The association of positive HLA-DQ2/DQ8 and serologic testing has a high predictive value for CD. We suggest that symptomatic children with high titers of immunoglobulin (Ig)A tTG could be diagnosed as patients with CD without performing jejunal biopsy. In other children, HLA-DQ2/DQ8 could be useful to exclude the diagnosis of CD if negative. In cases of low IgA tTG titers or in patients with IgA deficiency, intestinal biopsy remains mandatory.

Serology in adults with celiac disease: limited accuracy in patients with mild histological lesions

Celiac disease (CD) is a gluten-triggered enteropathy, presenting with insidious clinical patterns. It can occasionally be diagnosed in asymptomatic subjects. Our aim was to define the relationship among symptoms at diagnosis, serological markers [tissue transglutaminase antibodies (tTGA), anti-endomysium antibodies (EMA) anti-actin antibodies (AAA)] and degree of mucosal damage. A total of 68 consecutive adult patients with CD were enrolled. Intestinal biopsies were scored according to the Marsh classification modified by Oberhuber: I-II minimal lesions or absent villous atrophy; IIIA partial villous atrophy; IIIB-C total villous atrophy (TVA). HLA-typing was done for all patients. No association between clinical presentation and severity of mucosal damage was found. Presence of EMA or tTGA was significantly associated with more severe mucosal damage (P < 0.001). Of 12 patients, 11 with AAA were also positive for TVA. The severity of mucosal damage is the main factor governing the detectability of serological markers of CD. The sensitivity of serological testing is questionable in patients with minimal lesions.

Sarcoidosis and coeliac disease: do not forget the association!

A 70-year-old woman, with sarcoidosis localized in the lungs and cervical lymph nodes since 2008, presented to our open access Endoscopic Unit in May 2010 for colonoscopy due to iron deficiency anaemia (haemoglobin = 10.9 g/dL, MCV = 72 fl, iron = 25 mg/dL). The patient did not present any abdominal symptoms, and denied rectal bleeding. At colonoscopy, a 5 mm in diameter sessile polyp localized in the sigmoid colon was removed with the snare. Since no evident causes for anaemia were discovered, we suggested an upper endoscopy in the same endoscopic session to rule out other potential causes of blood loss. Surprisingly, reduced duodenal folds in the duodenum with ‘scalloping’ signs were found. Histological assessment of duodenal biopsies showed a total villous atrophy indicative of coeliac disease (CD), which was confirmed by positivity of both antiendomisium and anti-transglutaminase antibodies in the serum. The patient started a gluten-free diet obtaining a complete regression of anaemia in a few months. Sarcoidosis is a chronic idiopathic granulomatous disease as a consequence of altered immune response to unidentified antigens. Sarcoidosis mainly involves the lungs, even though other organs may be involved. Moreover, sarcoidosis has been associated with different autoimmune disorders, such as primary biliary cirrhosis, Crohn’s disease, and Sjogren’s syndrome [1]. An association between sarcoidosis and CD has been also described [2]. Although the mechanisms involved remain unclear, both diseases seem to share some immunological and genetic disorders. Indeed, the susceptibility of developing both sarcoidosis and CD has been linked to the class II haplotype HLA-DR3, DQ2 and B8 [3]. It is also possible that, by increasing the expression of class II HLA molecules, the diseases predispose to each other [3]. Thus the presence of CD may increase the risk of sarcoidosis development and vice versa [4, 5]. In detail, CD has been associated with an increased risk of sarcoidosis (HR = 4.03; 95% CI = 2.32–7.00). Similarly, a prior sarcoidosis diagnosis is associated with an increased risk of CD with an OR of 3.58 (95% CI = 1.98–6.45). Nevertheless, sarcoidosis often occurs in older subjects, while CD is more frequently observed in young people. Therefore, the association may not be observed by the physicians, especially when considering that CD in adults may present exclusively with an iron deficiency anaemia without any gastrointestinal symptoms, as was the case in our patient. In conclusion, CD should be promptly sought in all patients with sarcoidosis and a unexplained iron deficiency anaemia, before performing more invasive diagnostic tests.

Celiac disease in children and adolescents at a singe center in Saudi Arabia

BACKGROUND AND OBJECTIVES:Celiac disease (CD) is an immune-mediated enteropathy, induced by gluten in genetically susceptible individuals. The objective of this study was to describe the clinical pattern of CD in children from the western region of Saudi Arabia.DESIGN AND SETTING:Retrospective, hospital-based.PATIENTS AND METHODS:This study included children with a biopsy-proven diagnosis of CD made between September 2002 and July 2007. Children were admitted to the endoscopy unit for a small-bowel biopsy if they had gastrointestinal symptoms suggestive of CD or if they were positive for a CD-antibody screen performed for the high-risk groups.RESULTS:Eighty children were identified with a diagnosis of CD. Their mean (SD) age was 9.6 (4.9) years (range, 0.5-18 years). There were 44 (55%) female patients. Forty-one (51%) patients were detected during screening of high-risk groups, while 39 (49%) patients had classical symptoms of malabsorption. The screening also detected asymptomatic patients. Of 65 patients tested, 11 (17%) had elevated liver function tests, which reverted to normal after introduction of a gluten-free diet (GFD) except in one case. Seventy-three (91%) patients were positive for anti-tissue transglutaminase antibodies, 18 (23%), for IgG anti-gliadin antibodies; and 46 (58%), for IgA anti-gliadin antibodies. Forty-one (56%) patients showed good adherence to GFD as assessed by dietary history and the decline in anti-tTG level.CONCLUSION:CD may present with classical symptoms or be identified through screening programs. Growth and laboratory abnormalities usually improve after introduction of a GFD. Adherence to a GFD remains a problem; therefore, thorough assessment and counseling at the time of diagnosis and ongoing care are crucial.

Narrow-band imaging in the evaluation of villous morphology: a feasibility study assessing a simplified classification and observer agreement

To determine the utility of narrow-band imaging with optical magnification (NBI-Z) in the evaluation of villous morphology. Patients considered at risk of having celiac disease were invited. After standard endoscopy, they underwent further evaluation with NBI-Z which was digitally recorded. Targeted biopsies of each area videoed with NBI-Z were performed and tissue sent for histopathological analysis. Two expert endoscopists then selected the best representative videos (developmental phase). Next, 41 representative images of these videos were classified as follows: villous patterns present (N) or absent (A). Images showing absence of villi were then classified as cerebriform (C) or flat (F), corresponding to partial or total villous atrophy respectively. Three NBI-Z-naïve endoscopists then graded the videos. They underwent an interactive training session (learning phase) with video and images from a digital library before embarking on the actual assessment. To test for reproducibility, all videos were randomly reordered and graded again after a week. Forty-one videos (10 celiac disease, 31 normal) from 21 patients (3 celiac disease, 18 normal) were analyzed. The overall sensitivity and specificity in correctly distinguishing the presence or absence of villi were 93.3% and 97.8% respectively, with interobserver and intraobserver agreement (kappa, κ) at 0.82 and 0.86. The sensitivity and specificity in differentiating partial from total villous atrophy were 83.3% and 100%, κ at 0.73 and 0.68 respectively. Using a simplified classification, we demonstrated the feasibility of using NBI-Z to detect villous atrophy in patients presenting with suspected celiac disease.