Small intestinal biopsy findings consistent with celiac disease in patients with idiopathic inflammatory myopathy: Review of existing literature

BackgroundCase reports have described patients with idiopathic inflammatory myopathies (IIM) and a concurrent diagnosis of celiac disease (CeD) for whom the muscle inflammation (myositis) component of IIM improves after the patients start standard treatment with gluten-free diet (GFD). A connection between IIM and CeD is not commonly recognized.AimIn this first systematic review of the topic, we aimed to explore all peer-reviewed publications of IIM cases and concomitant small intestinal biopsy findings consistent with CeD, published after 1975.MethodsSystematic literature searches were performed in MEDLINE, PubMed, and EMBASE, supplemented by screening of references and non-systematic searches via Google and Google Scholar.ResultsAltogether 30 cases published between 1976 and 2017 were uncovered. Information about gastrointestinal symptoms prior to CeD diagnosis was available for 19 patients, with 6/19 (32%) reporting no GI symptoms. CeD-related serological data were available in 23/30 patients. Endomysial antibodies were present in 10/18 (56%), while only 2/9 (22%) had antibodies against tissue transglutaminase. Serum antibodies to native gliadin were present in 16/18 (89%). Clinical effects of a GFD on the IIM were reported for 24 patients, with signs of improvement in 14/24 (58%), including three patients with otherwise therapy-resistant inclusion body myositis. Longitudinal follow-up data available from the published studies indicated that 7/24 (29%) remained in clinical IIM remission with GFD as the sole therapeutic intervention.ConclusionIn the IIM cases presented here, duodenal biopsy findings consistent with celiac disease was sometimes present without classical CeD symptoms or positive traditional CeD serology, and in the majority of cases, the IIM improved after introduction of a gluten-free diet. While extra vigilance towards CeD in IIM patients seems warranted, there is need for more research to clarify if GFD has effects on organ systems other than the small intestine in patients with IIM and small intestinal biopsy findings consistent with CeD.     

Non-responsive celiac disease in children on a gluten free diet

BACKGROUNDNon-responsive celiac disease (NRCD) is defined as the persistence of symptoms in individuals with celiac disease (CeD) despite being on a gluten-free diet (GFD). There is scant literature about NRCD in the pediatric population.AIMTo determine the incidence, clinical characteristics and underlying causes of NRCD in children.METHODSRetrospective cohort study performed at Boston Children’s Hospital (BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh III histology between 2008 and 2012 were identified in the BCH’s Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo (responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy.RESULTSSix hundred and sixteen children were included. Ninety-one (15%) met criteria for NRCD. Most were female (77%). Abdominal pain [odds ratio (OR) 1.8 95% confidence interval (CI) 1.1-2.9], constipation (OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension (OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure (30%) and constipation (20%) being the most common causes. Other causes for NRCD included lactose intolerance (9%), gastroesophageal reflux (8%), functional abdominal pain (7%), irritable bowel syndrome (3%), depression/anxiety (3%), eosinophilic esophagitis (2%), food allergy (1%), eating disorder (1%), gastric ulcer with Helicobacter pylori (1%), lymphocytic colitis (1%), aerophagia (1%) and undetermined (13%). 64% of children with NRCD improved on follow-up.CONCLUSIONNRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.     

Clinical features and psychological impact of celiac disease at diagnosis

Background and aimWe aimed to describe the socio-demographic, behavioral and clinical profiles of adult patients with newly diagnosed celiac disease (CeD) and their possible association with QoL and psychological symptoms.MethodsAdults newly diagnosed with CeD and residents in the Veneto region were included. Their sociodemographic characteristics, clinical presentation, mode of diagnosis, duration of symptoms before diagnosis and comorbidities were recorded. All patients completed the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI) and Short Form Health Survey (SF-36) questionnaires.ResultsBetween 2016 and 2019, 110 CeD patients (81% females, mean age 37.5) were recruited. At diagnosis, patients were categorized into classical (n = 56), nonclassical CeD (n = 49) and asymptomatic (n = 5) groups. Patients with classical presentation had a lower QoL than nonclassical patients, who were found to be more depressed. We observed a diagnosis delay of more than 7 months in more than 60% of patients with both classical and nonclassical presentations and we found that a longer duration of GI symptoms decreased the self-reported SF36 scores in the physical health (p = 0.002), social functioning (p = 0.03) and general health (p = 0.009) domains. Women had an overall lower self-perceived QoL.ConclusionsSymptomatic presentation at CeD diagnosis, diagnostic delay and sex may affect QoL and psychological disorders.     

Antitissue transglutaminase antibodies’ normalization after starting a gluten-free diet in a large population of celiac children-a real-life experience

IntroductionFew data are available regarding the trend of IgA anti-transglutaminase antibodies (TGA-IgA) in children with celiac disease (CD) on a gluten-free diet (GFD). Our aim is to examine the normalization time of CD serology in a large pediatric population, and its predictors.Material and methodsWe retrospectively evaluated the normalization time of TGA-IgA and its predictive factors (age, sex, ethnicity, symptoms, associated diabetes/thyroiditis, Marsh stage, TGA-IgA and endomysial antibody levels at diagnosis, diet adherence), in 1024 children diagnosed from 2000 to 2019 in three pediatric Italian centers, on a GFD.ResultsTGA-IgA remission was reached in 67,3%, 80,7%, 89,8% and 94,9% after 12, 18, 24 and 36 months from starting a GFD, respectively (median time = 9 months). TGA-IgA >10´upper limit of normal at diagnosis (HR = 0.56), age 7–12 years old (HR = 0.83), poor compliance to diet (HR = 0.69), female sex (HR = 0.82), non-Caucasian ethnicity (HR = 0.75), and comorbidities (HR = 0.72) were independent factors significantly associated with longer time to normalization.ConclusionsOur population is the largest in the literature, with the majority of patients normalizing CD serology within 24 months from starting a GFD. We suggest a special attention to patients with comorbidities, language barriers or age 7–12 years for a proper management and follow-up.     

Changes in body mass index on a gluten-free diet in coeliac disease: a nationwide study

ObjectiveThe clinical presentation of coeliac disease has changed and patients are often overweight at diagnosis. There is concern that patients might gain further weight while on a gluten-free diet (GFD). The aim of the study was to evaluate the impact of a GFD on the body mass index (BMI) in a nationwide cohort of coeliac patients and to determine variables predictive of favourable or unfavourable BMI changes.MethodsWe prospectively investigated weight and disease-related issues in 698 newly detected adults diagnosed due to classical or extraintestinal symptoms or by screening. BMI at diagnosis and after one year on a GFD were assessed and compared with that in the general population.ResultsAt diagnosis, 4% of subjects were underweight, 57% normal, 28% overweight and 11% obese. On a GFD, 69% of underweight patients gained and 18% of overweight and 42% of obese lost weight; in the rest BMI remained stable. Changes were similar in both symptom- and screen-detected patients. The coeliac group had a more favourable BMI pattern than the general population. Favourable BMI changes were associated with subjects' self-rated expertise on GFD and young age at diagnosis, but not dietary counselling received.ConclusionsBMI improved similarly in screen- and symptom-detected coeliac disease patients on a GFD.     

Small intestinal bacterial overgrowth among patients with celiac disease unresponsive to a gluten free diet

Background/AimsLittle is known about the relationship between small intestinal bacterial overgrowth (SIBO) and celiac disease (CeD) in patients who are unresponsive to a gluten-free diet (GFD). This study aimed to determine the SIBO prevalence in patients with CeD who are unresponsive to a GFD.Materials and MethodsWe conducted a case-control study from July 2012 to September 2014. We included 32 patients with CeD who were unresponsive to a GFD and 52 healthy age- and sex-matched controls. Demographic, clinical, and laboratory data were obtained from patients’ medical records. Antitissue transglutaminase antibody determined by enzyme-linked immunosorbent assay was recorded, and lactulose hydrogen breath test (LHBT) was used to detect SIBO in all participants. Microbiological analysis, including jejunal aspirates obtained using upper endoscopy, was performed for only 20 patients with CeD.ResultsA total of 10 (31%) of 32 patients with CeD and 4 (7.7%) of 52 controls tested positive for LHBT, with a statistically significant difference (p=0.007). Of 20 cultures, 3 (15%) were positive with no statistically significant correlation between the cultures and LHBT (p=0.05). In a subgroup analysis of children who were 18 years old or younger, 7/24 (29.2%) patients with CeD had a positive LHBT compared with 3/32 (9.4%) controls, but this difference was not statistically significant (p=0.08).ConclusionThe prevalence of SIBO was 31% in unresponsive patients with CeD according to LHBT and 15% in the quantitative culture of the jejunal aspirate, which is comparable with the published Western literature     

Self-reported dietary adherence,disease-specific symptoms,and quality of life are associated with healthcare provider follow-up in celiac disease

Background

The only treatment for celiac disease (CeD) is a lifelong gluten-free diet (GFD). The restrictive nature of the GFD makes adherence a challenge. As an integral part of CeD management, multiple professional organizations recommend regular follow-up with a healthcare provider (HCP). Many CeD patients also participate in patient advocacy groups (PAGs) for education and support. Previous work found that follow-up of CeD patients is highly variable. Here we investigated the self-reported factors associated with HCP follow-up among individuals diagnosed with CeD who participate in a PAG.

Methods

We conducted a survey of members of Beyond Celiac (a PAG), collecting responses from 1832 U.S. adults ages 19–65 who reported having CeD. The survey queried HCP follow-up related to CeD and included validated instruments for dietary adherence (CDAT), disease-specific symptoms (CSI), and quality of life (CD-QOL).

Results

Overall, 27% of respondents diagnosed with CeD at least five years ago reported that they had not visited an HCP about CeD in the last five years. The most frequent reason for not visiting an HCP was “doing fine on my own” (47.6%). Using multiple logistic regression, we identified significant associations between whether a respondent reported visiting an HCP about CeD in the last five years and the scores for all three validated instruments. In particular, as disease-specific symptoms and quality of life worsened, the probability of having visited an HCP increased. Conversely, as dietary adherence worsened, the probability decreased.

Conclusions

Our results suggest that many individuals with CeD manage their disease without ongoing support from an HCP. Our results thus emphasize the need for greater access to high quality CeD care, and highlight an opportunity for PAGs to bring together patients and HCPs to improve management of CeD.

     

Risk perception and knowledge of COVID-19 in patients with celiac disease

BACKGROUNDWe recently demonstrated that the odds of contracting coronavirus disease 2019 (COVID-19) in patients with celiac disease (CeD) is similar to that of the general population. However, how patients with CeD perceive their COVID-19 risk may differ from their actual risk.AIMTo investigate risk perceptions of contracting COVID-19 in patients with CeD and determine the factors that may influence their perception.METHODSWe distributed a survey throughout 10 countries between March and June 2020 and collected data on demographics, diet, COVID-19 testing, and risk perceptions of COVID-19 in patients with CeD. Participants were recruited through various celiac associations, clinic visits, and social media. Risk perception was assessed by asking individuals whether they believe patients with CeD are at an increased risk of contracting COVID-19 when compared to the general population. Logistic regression was used to determine the influencing factors associated with COVID-19 risk perception, such as age, sex, adherence to a gluten-free diet (GFD), and comorbidities such as cardiac conditions, respiratory conditions, and diabetes. Data was presented as adjusted odds ratios (aORs)RESULTSA total of 10737 participants with CeD completed the survey. From them, 6019 (56.1%) patients with CeD perceived they were at a higher risk or were unsure if they were at a higher risk of contracting COVID-19 compared to the non-CeD population. A greater proportion of patients with CeD perceived an increased risk of contracting COVID-19 when compared to infections in general due to their CeD (56.1% vs 26.7%, P < 0.0001). Consequently, 34.8% reported taking extra COVID-19 precautions as a result of their CeD. Members of celiac associations were less likely to perceive an increased risk of COVID-19 when compared to non-members (49.5% vs 57.4%, P < 0.0001). Older age (aOR: 0.99; 95%CI: 0.99 to 0.99, P < 0.001), male sex (aOR: 0.84; 95%CI: 0.76 to 0.93, P = 0.001), and strict adherence to a GFD (aOR: 0.89; 95%CI: 0.82 to 0.96, P = 0.007) were associated with a lower perception of COVID-19 risk and the presence of comorbidities was associated with a higher perception of COVID-19 risk (aOR: 1.38; 95%CI: 1.22 to 1.54, P < 0.001).CONCLUSIONOverall, high levels of risk perceptions, such as those found in patients with CeD, may increase an individual’s pandemic-related stress and contribute to negative mental health consequences. Therefore, it is encouraged that public health officials maintain consistent communication with the public and healthcare providers with the celiac community. Future studies specifically evaluating mental health in CeD could help determine the consequences of increased risk perceptions in this population.     

Clinical symptoms in celiac patients on a gluten-free diet

Objective. Persistent villous atrophy in patients with celiac disease (CD) on a gluten-free diet (GFD) is reported with increasing frequency. The aim of this study was to evaluate a possible association between persistent damage of the villi and “atypical” gastrointestinal symptoms in CD patients on a GFD. Material and methods. Sixty-nine CD patients on a GFD were divided into two groups: Group A included 42 patients (6 M, 36 F, age range 17–62 years) undergoing esophagogastroduodenoscopies (EGDs) due to the presence of symptoms; Group B included 27 control patients (6 M, 21 F, age range 24–71 years) who were asymptomatic at the time of the study. Both groups underwent EGDs and a duodenal histologic study. Results. Persistent endoscopic lesions were more frequent in Group A (30/42) than in Group B (12/27; p=0.01). Villous atrophy was significantly more frequent in Group A than in Group B: 85% versus 33% (p<0.0001; odds ratio (OR)=12; 95% CI 3.7–38.9). Gastrointestinal symptoms in the Group A patients were different from those present at CD diagnosis: anemia/diarrhea/weight loss in 6 cases; gastroesophageal reflux disease (GERD)-like symptoms in 12 cases; abdominal pain/constipation in 24 cases. In Group A there was no difference in gender distribution, age and duration of GFD between subjects with normal villi and those with persistent partial villous atrophy. Patients with persistent symptoms showed a higher intraepithelial eosinophil count (p=0.005) than the asymptomatic patients (p=0.01). Conclusions. Persistent intestinal villous atrophy in CD patients on a GFD is associated with gastrointestinal symptoms considered “atypical” for CD and not present at CD diagnosis.     

Bone Mineral Density Screening and the Frequency of Osteopenia/Osteoporosis in Turkish Adult Patients With Celiac Disease

Background: The aim of this study was to evaluate the prevalence of osteopenia and osteoporosis in adult patients with celiac disease (CD) at diagnosis and/or in the follow-up after a gluten-free diet (GFD).MethodsAdult patients diagnosed with CD were retrospectively screened through follow-up records and computer databases. Patients assessed by dual-energy X-ray absorptiometry (DEXA) at diagnosis and/or in the follow-up after a GFD were included in the study.Results: One hundred patients who underwent a DEXA scan at least once after diagnosis or after being on a GFD were included in the study. The mean age of the patients at diagnosis was 34.61 ± 10.3 years, and 84% of the patients (n = 84) were female. At the time of diagnosis (n = 46), the prevalence of osteopenia and osteoporosis was 67.3% and 15.2%, respectively, at the lumbar spine, and 43.4% and 10.8%, respectively, at the femur. After a GFD (n = 78), the prevalence of osteopenia and osteoporosis was 61.5% and 8.9%, respectively, at the lumbar spine, and 37.1% and 2.5%, respectively, at the femur. ConclusionThe prevalence of CD patients with low bone mineral density (BMD) is high after diagnosis and in the follow-up after a GFD. It is important for all patients with CD to undergo a DEXA scan to determine the follow-up and/or treatment characteristics.     

No major reduction in bone mineral density after long-term treatment of patients with Celiac Disease

BackgroundAt time of diagnosis, patients with celiac disease (CD) have been shown to have lower bone mineral density (BMD) than healthy controls. It is unclear whether adult patients with CD can regain a normal BMD after treatment with a gluten-free diet (GFD).MethodsPatients diagnosed with CD as adults, who had been treated with GFD for a minimum of two years, were examined by dual energy X-ray absorptiometry (DXA) to determine BMD at femoral neck and spine L2-4. Adherence to GFD was measured using the Celiac Disease Adherence Test (CDAT) scoring tool.Results143 CD patients underwent DXA assessment, mean age was 55.8 years and mean treatment duration was 9.3 years. 67% of the patients were women, and 51% of these were postmenopausal. The prevalence of low bone mass (Z-score ≤ −1.0) was 18.2% (95%CI: 12.7–25.3%) at femoral neck and 23.1% (95%CI: 16.9–30.6%) at spine L2-4. An increase in low bone density prevalence at spine L2-4 compared to the expected prevalence (p = 0.016) was limited to the postmenopausal women. In a multiple regression analysis, only postmenopausal status and poor adherence to GFD was independently associated with reduced bone density, this however limited to spine L2-4.ConclusionOur study shows a small increase in the prevalence of low bone density at lumbar spine limited to the postmenopausal women. The main finding is that the majority of the CD patients after two years of treatment with GFD had a normal bone density when adjusted for age, gender, ethnicity and weight.     

Changes and relationships of IGFS and IGFBPS and cytokines in coeliac disease at diagnosis and on gluten-free diet

Objective To evaluate changes and relationships of IGFs and IGFBPs, serum interleukin 6 (IL‐6) and tumour necrosis factor (TNF)‐α, and auxological parameters at diagnosis of coeliac disease (CD) and at 6 months and 12 months after starting a gluten‐free diet (GFD), compared with a control population. Patients Twenty patients were enrolled at diagnosis (9 male, 11 female; age 9·6 ± 0·8 years). A healthy population of 18 subjects (5 male, 13 female; age 11·3 ± 0·6 years) comparable for age, sex and pubertal status served as controls at baseline. Measurements Blood samples were taken at diagnosis, and at 6 months and 12 months after starting the GFD. Serum IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2, IGFBP‐3, IL‐6 and TNF‐α were measured using commercial kits. Height (Ht) standard deviation score (SDS), body mass index (BMI) SDS and Ht velocity SDS were evaluated at diagnosis and at 6 months and 12 months after starting GFD. Results In CD patients, both Ht SDS and BMI SDS increased during the first year of treatment, and Ht velocity SDS increased during the second 6 months of follow‐up (P < 0·05). At diagnosis, IGF‐I, IGF‐II and IGFBP‐3 were lower compared with controls, IGFBP‐1 was similar, IGFBP‐2, IL‐6 and TNF‐α were higher (P < 0·05). When on GFD, all peptides normalized and IGFBP‐1 decreased. The IGF‐I/IGFBP‐2 and IGF‐I/IGFBP‐3 molar ratios were significantly reduced at diagnosis compared with those of controls, but were increased for both groups when on GFD. Although there was no apparent abnormality at diagnosis, the IGF‐II/IGFBP‐2 molar ratio increased significantly on GFD. Ht velocity SDS was positively correlated with IGFBP‐3 (P < 0·05) and with the IGF‐I/IGFBP‐2 molar ratio (P < 0·05). Serum IL‐6 was negatively correlated with IGF‐I and positively with IGFBP‐1 (P < 0·05). Conclusions The data obtained from this study confirm changes in the IGF and cytokine systems at diagnosis of CD which tend to normalize on the gluten‐free diet. The two systems show relationships with each other and with linear growth.     

What are the clinical consequences of ‘potential’ coeliac disease?

BackgroundThere is limited data on the clinical consequences of potential coeliac disease (PCD).AimTo compare the presentation of PCD with coeliac disease (CD).MethodsA retrospective study of adult PCD patients (>18 years) was performed. Presenting manifestations, serology and HLA-DQ genotyping were compared to an age-at-diagnosis and sex-matched CD cohort.ResultsThe PCD cohort comprised 84 patients (median age 37 years, 63% female). The majority of PCD patients were symptomatic at presentation (PCD 91.7% versus CD cohort 94.0%, p = 0.55). In total, 79.8% and 76.2% of the PCD and CD cohorts respectively reported ≥1 gastrointestinal symptoms at presentation (p = 0.58). Extraintestinal presentation was less common in PCD than CD (65.5% versus 79.8% respectively, p = 0.038). PCD patients had fewer haematinic deficiencies than those with CD (iron 21.4% versus 41.7%, p = 0.005, vitamin D 14.3% versus 27.4%, p = 0.037 and folate deficiency 7.1% versus 28.6%, p= <0.001.) Post-diagnosis, 67.5% of the PCD patients chose a GFD. One-third of the patients who continued to eat gluten developed villous atrophy.ConclusionThe presentation of PCD and CD differ; however, mild enteropathy does not necessarily equate to mild symptoms. The GFD appears to be advantageous in symptomatic PCD.     

Children with untreated coeliac disease have sub-clinical cardiac dysfunction: a longitudinal observational analysis

Introduction: We assessed cardiac function (CF) in celiac disease (CD) patients and the effect of gluten-free diet (GFD) on CF.

Methods: Prospective evaluation of CF using conventional and tissue doppler echocardiography in 50 CD patients (age 4.2?±?1.1 years) at diagnosis and after a year of GFD (group 1), 100 CD children (group 2; 47 compliant and 53 non-compliant) in follow-up and 25 healthy controls.

Results: Untreated CD (n?=?50) children had larger left ventricle end diastolic dimension (35.33?±?0.87 vs. 32.90?±?0.91 mm; p?=?.04), reduced (<55%) left ventricular ejection fraction (20% vs. 0%; p?=?.01) and a higher (>0.6) myocardial performance index (MPI, 66% vs. 0%; p ≤ .01) as compared to controls. Re-evaluation after one year with good dietary compliance showed changes in isovolumic relaxation time (72.5?±?4.2 vs. 50.62?±?2.69; p?=?.0001) and deceleration time (121.05?±?10.1 vs. 99.87?±?8.5; p?=?.02), reflecting improved cardiac diastolic function. GFD compliant patients had lower MPI than non-compliant (0.60?±?.03 vs. 0.66?±?.08; p?=?.04), reflecting improvement in load-independent echocardiographic parameters.

Conclusions: Subclinical cardiac dysfunction is common in CD children at diagnosis. Improvement

in echocardiographic parameters occurs with GFD and non-compliant children continue to have

persistent cardiac dysfunction.     

The symptomatic and histologic response to a gluten-free diet in patients with borderline enteropathy

GOALS: A clinical problem is posed by patients with symptoms suggestive of gluten sensitivity (diarrhea, weight loss, unresponsive iron-deficiency anemia, etc.); however, small intestinal biopsies reveal only minor abnormalities, such as lymphocytosis with or without crypt hyperplasia (Marsh I-II). Our aim was to assess the benefit of a gluten-free diet (GFD) in patients with these small bowel mucosal abnormalities. STUDY: We studied 35 patients (11 men, 24 women; mean age, 28 years; range, 22-51 years) referred to us for gastrointestinal symptoms or unexplained or unresponsive diseases. Because celiac disease was suspected to be the underlying pathology, small intestinal biopsies were taken. These revealed only minor abnormalities: 11 patients showed Marsh I type lesions, whereas 24 patients demonstrated Marsh II type lesions. Although the histologic lesions were inconsistent for celiac disease and a suspicion of a borderline celiac disease persisted, all patients were motivated to adhere to GFD.RESULTS Only 23 patients adhered to our advice and followed a GFD; follow-up biopsies were taken after 8 to 12 months. In the Marsh I lesion group (seven patients), five patients showed mucosal normalization to Marsh 0 and two showed persistence of Marsh I lesions. In the Marsh II lesion group (16 patients), 9 patients revealed mucosal normalization, 5 improved to a Marsh I lesion, and 3 revealed persistence of Marsh II lesions. A dramatic clinical improvement in symptoms was noted in all patients who were on a GFD, with symptoms virtually disappearing in all patients. Seven patients who refused GFD were reevaluated 8 to 12 months later. Symptoms and histologic lesions were unchanged in six, all of whom refused again to adhere to a GFD. One of the seven with Marsh I lesions had a worsening of symptoms and of histologic lesions (from Marsh I to Marsh IIIa); so, this last patient adhered to a GFD. CONCLUSIONS: Symptoms disappeared after GFD in patients suspected to have celiac disease but with slight histologic lesions. Although Marsh I-II lesions cannot be classified as celiac lesions (ESPGAN criteria), the patients' symptoms at presentation and the clear improvement of symptoms when on GFD, with or without improvement of histologic lesions, supports the assumption that these patients are sensitive to gluten and may justify treatment with a GFD.     

Changes of body mass index in celiac children on a gluten-free diet

Background and aimStudies of adults and children with celiac disease (CD) performed mostly in tertiary care centers have reported an increased risk of overweight during gluten-free diet (GFD). We measured body mass index (BMI) of CD children followed by family pediatricians in order to estimate prevalence of underweight and overweight at diagnosis and to describe BMI changes during GFD.Methods and ResultsWe compared 150 CD children (age range 2–16 yrs) under GFD from a median (IQR) time of 4.4 (4.2) years with 288 healthy children matched for gender and age. We also evaluated retrospectively BMI changes between CD diagnosis and the current evaluation. The median (IQR) BMI of CD patients was significantly lower than that of controls [?0.38 (1.46) vs. 0.09 (1.18) SDS, p < 0.0001, Italian reference data]. Using the International Obesity Task Force classifications, CD children were less frequently overweight or obese (12% vs. 23.3%, p = 0.014) and more frequently underweight (16% vs. 4.5%, p < 0.001) than controls. During GFD, there was a marked decrease of number of underweight subjects (13 vs. 27) and a minimal increase of number of overweight subjects (9 vs. 6) (p < 0.001).ConclusionsThe frequency of overweight and obesity at diagnosis of CD and during GFD in children followed by family pediatricians is substantially lower than that reported in tertiary care centers. On the other hand, the high frequency of underweight at diagnosis confirms the need of careful personalized nutritional management.     

Synovial sarcomas in Lugo between 2002-2006

ObjectiveTo study the clinical and epidemiological characteristics of all adults patients as having synovial sarcoma in the Hospital Xeral-Calde (Lugo) between 2002 and 2006.Patients and methodWe conducted a retrospective study of the case records of all adults patients diagnosed with synovial sarcoma from January 2002 through December 2006. Patients were considered to be adults if they were more than 18. In all cases a tissue-biopsy sample showing synovial sarcoma was required. The Hospital Xeral-Calde is the only referral center for a population of almost 250.000 people.ResultsFour cases (3 women) met the classification criteria for this study. The mean age was 35 years old (range, 22–41).The most common presentation was a palpable mass (mean 6.7 cm.) associated with pain in lower extremities. The mean delay for the diagnosis was 17 months, but in one case has been noted as long as 2.5 years. Unlike the neck synovial sarcoma case, a long delay in the diagnosis implied a major tumor size and a higher histologic grade.The mean follow-up was 25.5 months; one patient died 1.5 years after the diagnosis.ConclusionsThe overall annual incidence rate of synovial sarcoma in the Lugo region between January 2002 and 2006 for the population older than 18 years was a minimum estimate 0.32/10⁵. Better physician awareness may contribute to the progressive increase in the recognition of this condition, especially in young people presenting with palpable mass. A long delay at the diagnosis implied a poor prognosis.     

Non-diarrheal celiac disease: a report of 31 cases from northern India.

BACKGROUND AND AIMS: Non-diarrheal presentation of celiac disease (CD) is being increasingly recognized. Data on this form of CD from India are limited. METHODS: Consecutive patients with CD presenting to a tertiary referral center in northern India over a 3-year period were studied, with special emphasis on non-diarrheal celiac disease (NDCD). Diagnosis was based on the presence of autoantibodies typical of CD (IgA anti-tissue transglutaminase antibodies and/ or IgA endomysial antibodies), abnormal duodenal biopsy and response to gluten-free diet (GFD). Clinical, hematological and histological responses were assessed over a one-year period after instituting GFD. RESULTS: Of 86 patients with CD, 31 (16 children, 15 adult) had NDCD. Mean (SD) age of these children (12 boys) and adults (4 male) was 10.2 (4.2) y and 35.3 (12.0) y, respectively. Failure to thrive was the most common (11/16) presentation in children, as was refractory anemia in adults (10/15). Malabsorption was found in 8 adults (54%) and 10 children (64%) with NCCD. The duration from onset of symptoms to diagnosis was 2.9 (1.5) y in children and 3.3 (0.3) y in adults. There was significant improvement in body weight (children--baseline 18.9 [5.8] Kg, follow up 27.4 [12.4] Kg; adults--baseline 47.6 [18.2] Kg, follow up 54.9 [5.1] Kg) and hemoglobin (children--8.1 [2.0] g/dL to 11.2 [1.4] g/dL; adults--7.3 [2.3] g/dL to 9.7 [1.7] g/dL) in both groups after one year of GFD; duodenal biopsy also improved, with a majority of patients attaining normal to IIIa Marsh grading. Five adults and all children had evidence of metabolic bone disease at presentation, which did not revert completely with GFD. Eight adults and nine children showed dietary transgression 6 weeks after starting GFD. CONCLUSION: NDCD ac-counted for nearly one-third of all cases with CD at our center, with 'failure to thrive' and refractory anemia being the most common presentations in children and adults, respectively.     

Anti-microbial antibodies in celiac disease： Trick or treat？

AIM： To determine the prevalence of a new set ot anti-glycan and anti-outer membrane protein （anti- OMP） antibodies in a Hungarian cohort of adult Celiac disease （CD） patients. METHODS： 190 consecutive CD patients [M/F： 71/119, age：39.9 （SD：14.1） years], 100 healthy, and 48 gastrointestinal controls were tested for glycan anti-Saccharomyces cerevisiae （gASCA）, anti-laminaribioside （ALCA）, anti-chitobioside, anti-mannobioside, anti-OMP antibodies and major NOD2/CARD15 mutations. Thirty out of 82 CD patients enrolled at the time of diagnosis were re-evaluated for the same antibodies after longstanding gluten-free diet （GFD）. RESULTS： 65.9% of the CD patients were positive for at least one of the tested antibodies at the time of the diagnosis. Except anti-OMP and ALCA, antimicrobial antibodies were exclusively seen in untreated CD; however, the overall sensitivity was low. Any glycan positivity （LR＋： 3.13; 95% CI： 2.08-4.73） was associated with an increased likelihood ratio for diagnosing CD. Significant correlation was found between the levels of anti-glycan and anti-endomysial or anti-transglutaminase antibodies. Anti-glycan positivity was lost after longstanding GFD. Anti-glycan antibody titers were associated with symptoms at presentation, but not the presence of NOD2/CARD15 mutations. Patients with severe malabsorption more frequently had multiple antibodies at diagnosis （P = 0.019）. CONCLUSION： The presence of anti-glycan antibodies in CD seems to be secondary to the impaired small bowel mucosa which can lead to increased antigen presentation. Furthermore, anti-glycan positivity may be considered an additional marker of CD and dietary adherence.     

Effect of a gluten‐free diet on plasma nitric oxide products in coeliac disease

Background: Inducible nitric oxide synthase is expressed in the small intestine of patients with coeliac disease. This produces increased plasma concentration of nitric oxide end products (NOx), most marked in those ingesting gluten. The time‐course of change in NOx with a gluten‐free diet (GFD) and its correlation with histology and coeliac serology were studied. Methods: Fasting plasma NOx was determined by the Greiss reaction in 20 coeliac patients at diagnosis and 2, 4 and 6 months after commencing a GFD. Endomysial and gliadin antibodies were checked at the same time. Duodenal biopsies were taken at diagnosis and at 6 months, and then graded according to the Marsh classification. Results: Plasma NOx fell rapidly following the introduction of a GFD (mean before GFD 95.8?μM to 61.5?μM at 2 months), and further still by 6 months (mean?=?37.0?μM). Reductions at 2 and 6 months were statistically significant compared with baseline (P?P?x was correlated with histological grade initially (P?=?0.03: Kruskal‐Wallis) but not after 6 months on a GFD (P?=?0.24). Coeliac serology correlated poorly with histology. Conclusions: Plasma NOx falls rapidly following GFD in coeliac disease and is related to histological grade initially. However, values vary widely between individuals, which may limit its use as a clinical tool.