Assessment of QRS duration and presence of fragmented QRS in patients with celiac disease.

Background: Celiac Disease (CD) is characterized by small intestine involvement. However, cardiac manifestations may also be seen in the clinical course. The significance of the QRS prolongation and the presence of QRS fragmentation (fQRS) has been previously studied in many chronic inflammatory disorders as an independent predictor of cardiac manifestations. The study aimed to evaluate the QRS duration and presence of fQRS in patients with CD. Methods: 164 patients with CD and 162 healthy controls were included in the present study. QRS duration and presence of fQRS were calculated from the 12-lead electrocardiogram and compared between groups. The association between these parameters and disease duration was also evaluated. Results: QRS duration was found to be higher in the CD group compared to the control group (83 (76.8-93) vs. 91 (84-94), p<0.001). The presence of fQRS was demonstrated to be higher in the CD group (n=68 (41.5%) vs n=42 (25.9%), p=0.003). Notably, QRS duration was positively correlated with disease duration (Spearman's Rho= 0.47, p<0.001). In addition, disease duration was significantly higher in the fQRS (+) group (60 (23,5-144) vs. 28,5 (15-71,5), p=0.002). Conclusion: This study revealed that QRS prolongation and the presence of fQRS were higher in patients with CD. The presence of these findings may be an indicator of early subclinical cardiac involvement, especially in those with long disease duration. Thus, patients with these ECG findings can be considered for further cardiac evaluation.

Bone Health in Premenopausal Women with Coeliac Disease: An Observational Study.

Low bone mineral density (BMD) is common in adults with coeliac disease (CD), even in individuals adhering to a gluten-free diet (GFD). Women are more likely to have low BMD and have an increased risk of osteoporosis, so women with pre-existing low BMD related to CD are at an even higher risk. BMD assessed by dual X-ray absorptiometry (DXA) and bone quality assessed through quantitative ultrasound (QUS) were investigated in 31 premenopausal women with CD consuming a GFD, and 39 matched healthy controls from the Lower North Island, New Zealand. In addition, bone metabolism and nutrient status were assessed, and four-day diet diaries were used to estimate nutrient intake. No statistically significant differences were found in BMD assessed by DXA between the two groups at the hip, lumbar spine or forearm. However, the parameters measured by the QUS were significantly lower in CD participants. Dietary data indicated significantly lower intakes of energy, dietary fibre, magnesium and phosphorus in women with CD, likely as a result of a reduced intake of wholegrain foods, and suggested that both groups had inadequate intake of calcium. No significant differences were demonstrated in biochemical parameters. BMD and bone biomarkers indicated no differences between coeliac and healthy women in New Zealand. However, these findings suggest that QUS may be more sensitive for the coeliac population, due to the disease's affect on the trabecular bone, and warrant further research.

Evaluation of Hearing Functions in Children with Celiac Disease and the Effect of Gluten-free Diet on these Functions.

OBJECTIVE: The present study aims to investigate the potential impact of celiac disease (CD) on hearing functions and assess the effect of a gluten-free diet (GFD) on this condition. MATERIALS AND METHODS: The study included 55 children with CD (110 ears) and 25 healthy controls (50 ears) matched for age and gender. The CD group was divided into adherent (n = 31) and nonadherent (n = 24) to GFD. Participants underwent tympanometry and pure tone audiometry assessments covering frequencies from 500 to 4000 Hz. RESULTS: Patients with CD showed significantly higher air and bone conduction hearing averages compared to the control group at frequencies of 500, 1000, 2000, and 4000 Hz for air conduction, and at 500 Hz for bone conduction (P < 0.05). Celiac patients, those who fully adhered to GFD, had notably higher air conduction hearing averages at 500, 2000, and 4000 Hz compared to healthy controls (P < 0.05). However, there was no difference in bone conduction hearing averages between the two groups. In contrast, celiac patients who did not comply with GFD had statistically significantly higher air and bone conduction hearing averages than the control group (P < 0.05), at frequencies of 500, 1000, and 4000 Hz for air conduction, and at 500 and 1000 Hz for bone conduction (P < 0.05). CONCLUSIONS: The study suggests that nonadherence to GFD may elevate the risk of hearing loss in children with CD. As a result, it is recommended to conduct hearing screenings for children with CD and underscore the importance of complying with GFD to mitigate further detrimental effects on hearing functions.

Reproductive functions and pregnancy outcome in female patients with celiac disease.

BACKGROUND AND AIM: Abnormalities in the reproductive functions are often ignored while evaluating a patient with celiac disease (CeD). We evaluated the entire reproductive functions in female patients with CeD. METHODS: In a case control study between 2020 and 2021 using detailed questionnaire, we evaluated reproductive functions (age at menarche, menstrual pattern, fertility, pregnancy outcome and menopause) in biopsy-proven female patients with CeD of age >10 years. The questionnaire was administered either in person or telephonically. Age-matched healthy female controls (twice the number) were also recruited. RESULTS: Of 1086 CeD patients, 470 were females and 288 were included. As compared with controls (n = 586), females with CeD had higher age at menarche (14.6 ± 2.0 vs 13.6 ± 1.5 years; P = 0.001), delayed menarche (30.8% vs 11.4%; P = 0.001), abnormal menstrual pattern (39.7% vs 25.8%; P < 0.001), involuntary delay in conception at > 1 year (33.8% vs 11.8%; P = 0.01), current infertility rate (10.5% vs 5.2%;P = 0.028), and poorer overall pregnancy outcomes (abortion [23.5% vs 12.8%; P = 0.001], pre-term birth [16.3% vs 3.7%; P = 0.001]). CONCLUSIONS: Either one or more aspect of reproductive functions and pregnancy outcome is affected adversely in three-fourth female patients with CeD.

Development and validation of a brain fog scale for coeliac disease.

BACKGROUND: Brain fog is a subjective cognitive impairment commonly reported in coeliac disease. A standardised tool to define and assess it is an important unmet need. AIMS: To develop a patient-informed tool to assess brain fog in coeliac disease to support clinical care, research and drug development. METHODS: A pilot online study defined patient descriptors of brain fog. A second study evaluated the factor structure and performance of the scale across two-time points ('Now' and in the 'Past week'). One month later, participants were invited to repeat the study with two online cognitive processing tests, the Stroop task and the trail making test. RESULTS: Among adults with treated coeliac disease, 37 (91.9% F) participated in the pilot study and 510 (88.8% F) in the second study of whom 99 repeated the study 1 month later with 51 completing cognitive testing. The most common brain fog descriptors were 'difficulty focusing', 'difficulty thinking' and 'difficulty finding the right words and communicating'. The 12-item scale reflects 'cognitive impairment' and 'somatic and affective experience' and demonstrates strong psychometric properties. It tracked with patients report of brain fog being present or absent across two-time points. It did not significantly correlate with the cognitive tests. CONCLUSION: The brain fog assessment and severity scale is the first patient-informed clinical outcomes assessment tool measuring brain fog in coeliac disease. It is brief and validated for two time-based formats. Further research coupling it with biomarker discovery is needed to confirm its validity as a predictor of cognitive performance.

Celiac disease in children and adolescents with Down syndrome: behavioural, adaptive and sleep profiles.

BACKGROUND: Individuals with Down syndrome (DS) exhibit higher risk for celiac disease (CD) than general population. Although literature suggests CD could be associated with behavioural problems in both paediatric and adult age, such association has been poorly explored in children and adolescents DS. Therefore, the current study aimed to investigate differences in emotional/behavioural difficulties, adaptive skills and sleep problems between children with DS with and without CD. METHODS: Data were retrospectively collected from a database including data from 381 individuals with DS (3-18 years). The final sample included 65 participants, 27 with co-occurring CD and 38 age, IQ, sex and body mass index-matched controls without CD. Emotional/behavioural difficulties, adaptive skills and sleep problems were assessed through parent report questionnaires. RESULTS: No group differences emerged in emotional/behavioural difficulties, whereas participants in the CD group showed better adaptive skills in the practical domain than control group. Weak differences emerged in sleep problems. CONCLUSIONS: Youth with DS and co-occurring CD do not exhibit more emotional and behavioural problems than youth with DS without co-occurring CD but exhibit better adaptive skills in the practical domain.

A significant increase in anthropometric indices during long-term follow-up of pediatric patients with celiac disease, with no endocrine disorders.

Celiac disease (CeD) is likely to be associated with growth impairment and poor weight gain. However, long-term growth patterns following diagnosis are poorly characterized. We evaluated long-term anthropometric changes in a large cohort of pediatric patients with CeD. A retrospective chart review of patients diagnosed with CeD between 1999 and 2018 was conducted. Demographic and clinical data were collected, and anthropometrics were analyzed from diagnosis and throughout follow-up. The study included 500 patients (59.8% females, median (IQR) age at diagnosis 5.7 (3.7-8.9) years), with a mean follow-up of 5.5 (range 1.5-16.2) years. Weight, height, and BMI Z-score-for-age (WAZ, HAZ, and BMIZ) increased significantly from a mean (± SD) of - 0.82 (± 1.21), - 0.73 (± 1.16), and - 0.32 (± 1.11) at diagnosis to - 0.41 (± 1.23), - 0.45(± 1.16), and - 0.17 (± 1.14) at last follow-up, respectively (p < 0.001 for WAZ and HAZ and p = 0.002 for BMIZ). The largest improvements were observed in patients diagnosed before 3 years of age (p < 0.01). Patients for whom the final adult height was available (n = 86) improved from HAZ mean (± SD) - 0.89 ± 1.37 at diagnosis to - 0.51 ± 1.28 at adulthood measurement, p < 0.05. Wasting was present in 19.7% and stunting in 16.4% of the cohort at diagnosis and normalized in 77.3% and 64.8%, respectively, within a median (IQR) time of 0.79 (0.42-4.24) and 2.3 (0.72-6.02) years, respectively. Gluten-free diet adherence and frequency of visits were not associated with normalization of wasting or stunting in all age groups.  Conclusion: Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. Younger age at diagnosis is associated with greater improvement in weight and linear growth, emphasizing the importance of early diagnosis of CeD. What is Known: • Celiac disease (СeD) is likely to be associated with growth impairment and poor weight gain. • Long-term changes in anthropometric indices after diagnosis of CeD are not well characterized. What is New: • Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. • Young age at diagnosis is associated with larger improvement in weight and linear growth.

Fungal Dysbiosis in Children with Celiac Disease.

BACKGROUND: Although intestinal fungi are known to interact with the immune system, the relationship between intestinal fungi and childhood celiac disease (CeD), an immune-mediated condition, has rarely been reported. AIMS: The aim of this study was to describe gut fungal profiles in a cohort of children with new-onset CeD. METHODS: Mucosal and fecal samples were collected from children with CeD and controls and subjected to metagenomics analysis of fungal microbiota communities. DNA libraries were sequenced using Illumina HiSeq platform 2 × 150 bp. Bioinformatic analysis was performed to quantify the relative abundance of fungi. Shannon alpha diversity metrics and beta diversity principal coordinate (PCo) analyses were calculated, and DESeq tests were performed between celiac and non-celiac groups. RESULTS: Overall more abundant taxa in samples of children with CeD included Tricholomataceae, Saccharomycetaceae, Saccharomycetes Saccharomyces cerevisiae, and Candida, whereas less abundant taxa included Pichiaceae, Pichia kudriavzevii, Pneumocystis, and Pneumocystis jirovecii. Alpha diversity between CeD and control individuals did not differ significantly, and beta diversity PCo analysis showed overlap of samples from CeD and controls for both fecal or mucosal samples; however, there was a clear separation between mucosal and fecal overall samples CONCLUSIONS: We report fungal dysbiosis in children with CeD, suggesting a possible role in the pathogenesis of CeD. Further larger, controlled, prospective and longitudinal studies are needed to verify the results of this study and clarify the functional role of fungi in CeD.

Preserved central cholinergic functioning to transcranial magnetic stimulation in de novo patients with celiac disease.

BACKGROUND: Celiac disease (CD) is now viewed as a systemic disease with multifaceted clinical manifestations. Among the extra-intestinal features, neurological and neuropsychiatric symptoms are still a diagnostic challenge, since they can precede or follow the diagnosis of CD. In particular, it is well known that some adults with CD may complain of cognitive symptoms, that improve when the gluten-free diet (GFD) is started, although they may re-appear after incidental gluten intake. Among the neurophysiological techniques, motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) can non-invasively probe in vivo the excitation state of cortical areas and cortico-spinal conductivity, being also able to unveil preclinical impairment in several neurological and psychiatric disorders, as well as in some systemic diseases affecting the central nervous system (CNS), such as CD. We previously demonstrated an intracortical disinhibition and hyperfacilitation of MEP responses to TMS in newly diagnosed patients. However, no data are available on the central cholinergic functioning indexed by specific TMS measures, such as the short-latency afferent inhibition (SAI), which might represent the neurophysiological correlate of cognitive changes in CD patients, also at the preclinical level. METHODS: Cognitive and depressive symptoms were screened by means of the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively, in 15 consecutive de novo CD patients and 15 healthy controls. All patients were on normal diet at the time of the enrolment. Brain computed tomography (CT) was performed in all patients. SAI, recorded at two interstimulus intervals (2 and 8 ms), was assessed as the percentage amplitude ratio between the conditioned and the unconditioned MEP response. Resting motor threshold, MEP amplitude and latency, and central motor conduction time were also measured. RESULTS: The two groups were comparable for age, sex, anthropometric features, and educational level. Brain CT ruled out intracranial calcifications and clear radiological abnormalities in all patients. Scores at MoCA and HDRS were significantly worse in patients than in controls. The comparison of TMS data between the two groups revealed no statistically significant difference for all measures, including SAI at both interstimulus intervals. CONCLUSIONS: Central cholinergic functioning explored by the SAI of the motor cortex resulted to be not affected in these de novo CD patients compared to age-matched healthy controls. Although the statistically significant difference in MoCA, an overt cognitive impairment was not clinically evident in CD patients. Coherently, to date, no study based on TMS or other diagnostic techniques has shown any involvement of the central acetylcholine or the cholinergic fibers within the CNS in CD. This finding might add support to the vascular inflammation hypothesis underlying the so-called "gluten encephalopathy", which seems to be due to an aetiology different from that of the cholinergic dysfunction. Longitudinal studies correlating clinical, TMS, and neuroimaging data, both before and after GFD, are needed.

Changes in Diet and Anthropometric Parameters in Children and Adolescents with Celiac Disease-One Year of Follow-Up.

Celiac disease (CD) may cause numerous nutrient deficiencies that a proper gluten-free diet (GFD) should compensate for. The study group consists of 40 children, aged 8.43 years (SD 3.5), on average, in whom CD was diagnosed on the basis of clinical symptoms, immunological and histopathological results. The patients' height, weight, diet and biochemical tests were assessed three times: before diagnosis, after six months, and following one year of GFD. After one year, the patients' weight and height increased but nutritional status (body mass index, BMI percentile) did not change significantly. The children's diet before diagnosis was similar to that of the general Polish population: insufficient implementation of the dietary norm for energy, fiber, calcium, iodine, iron as well as folic acid, vitamins D, K, and E was observed. Over the year, the GFD of the children with CD did not change significantly for most of the above nutrients, or the changes were not significant for the overall assessment of the diet. Celiac patients following GFD may have a higher risk of iron, calcium and folate deficiencies. These results confirm the need for personalized nutritional education aimed at excluding gluten from the diet, as well as balancing the diet properly, in patients with CD.

Prevalence of migraine in adults with celiac disease: A case control cross-sectional study.

AIM: Celiac disease (CD) is an immune-mediated disorder with various manifestations. The aim of this study was to evaluate the prevalence of gastrointestinal (GI) and extra-intestinal symptoms of celiac patients, especially migraine, and compare it with healthy individuals. METHODS: We compared 1000 celiac subjects (CS) registered at our celiac center with the control group for headache-based on International Classification of Headache Disorders, third edition criteria and their GI symptoms. Besides, CS with migraine and non-migrainous headache were compared in terms of GI symptoms and accompanied conditions. RESULTS: Headache was more common in CS than controls (34% vs 27% respectively, P value<0.001) and more prevalent in females (71.9% in females vs 28% in males, P value = 0.004). Moreover, the prevalence of migraine in CS was higher than controls (20.7 vs 11.9% respectively, P value<0.001). Furthermore, migraine was more prevalent in females with CD (80% in females vs 19% in males, P value = 0.033), and often without aura (76%). Abdominal pain (76.9%, P value = 0.025), diarrhea (54.9%, P value = 0.002), and constipation (42.9%, P value = 0.011) were the most common GI symptoms in CS with headache and more prevalent in CS with migraine. Conversely, type 1 diabetes mellitus was less common in CS with migraine than in CS with non-migrainous headache. (P value = 0.001). On multivariate logistic regression analysis, female sex (OR 1.50, 95%CI 1.22-1.83, P value < 0.001), and CD (OR 1.36, 95%CI 1.12-1.65, P value = 0.002) were independent predictors of headache, whereas age more than 60 years (OR 0.70, 95%CI 0.50-0.97, P value = 0.032) had a protective effect. CONCLUSION: Headache especially migraine is more prevalent in CS than healthy controls. In addition, abdominal pain, diarrhea, and constipation are more common in CS with migraine than in CS with non-migrainous headaches. Therefore, evaluation of CD in patients with migraine and these simultaneous GI symptoms seems reasonable.

Prevalence and Clinical Features of Celiac Disease in a Cohort of Italian Children with Autism Spectrum Disorders.

BACKGROUND: Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions whose etiopathogenesis derives from a complex interaction between genetic liability and environmental factors. In this framework, mounting evidence suggests that immune system dysfunction could be a risk factor contributing to the development of ASD in at least a subpopulation of individuals. In particular, some studies suggest an association between celiac disease (CD)-a long-term autoimmune disorder that primarily affects the small intestine triggered by the ingestion of gluten-and ASD, while others hypothesized a random link. This investigation aimed to evaluate the prevalence of CD in a large sample of school-aged children with ASD and to characterize their clinical profile. METHODS: Medical records of 405 children with ASD aged 5-11 years (mean age: 7.2 years; SD: 1.8 years) consecutively referred to a tertiary-care university hospital between January 2014 and December 2018 were reviewed; among them, 362 had carried out serological testing for CD. RESULTS: Nine patients with positive CD serology were identified, eight of which satisfied the criteria for CD diagnosis. The estimated CD prevalence in ASD children was 2.18% (95% CI, 0.8-3.7), which was not statistically different (1.58%; p = 0.36) from that of an Italian population, matched for age range, considered as a control group (95% CI, 1.26-1.90). Three out of the eight ASD patients with CD did not have any symptoms suggestive of CD. CONCLUSIONS: Our findings did not show a higher prevalence of CD in ASD children than in the control population, but could suggest the utility of routine CD screening, given its frequent atypical clinical presentation in this population.

Society for the Study of Celiac Disease position statement on gaps and opportunities in coeliac disease.

Progress has been made in understanding coeliac disease, a relatively frequent and underappreciated immune-mediated condition that occurs in genetically predisposed individuals. However, several gaps remain in knowledge related to diagnosis and management. The gluten-free diet, currently the only available management, is not curative or universally effective (some adherent patients have ongoing duodenal injury). Unprecedented numbers of emerging therapies, including some with novel tolerogenic mechanisms, are currently being investigated in clinical trials. In March 2020, the Celiac Disease Foundation and the Society for the Study of Celiac Disease convened a consensus workshop to identify high-yield areas of research that should be prioritized. Workshop participants included leading experts in clinical practice, academia, government and pharmaceutical development, as well as representatives from patient support groups in North America. This Roadmap summarizes key advances in the field of coeliac disease and provides information on important discussions from the consensus approach to address gaps and opportunities related to the pathogenesis, diagnosis and management of coeliac disease. The morbidity of coeliac disease is often underestimated, which has led to an unmet need to improve the management of these patients. Expanded research funding is needed as coeliac disease is a potentially curable disease.

The expansion of CD14+ CD163+ subpopulation of monocytes and myeloid cells-associated cytokine imbalance; candidate diagnostic biomarkers for celiac disease (CD).

Celiac disease (CD) is a chronic autoimmune disorder of small intestine against dietary gluten, among genetically predisposed individuals. Monocytes are versatile innate immune cells involved in the regulation of inflammation, and strongly involved in the intestinal immunity. However, the role of monocytes and their subtypes in CD is not well demonstrated. METHODS: Here, we assessed the polarization of CD14+ monocytes by evaluating the M1 (CD16) and M2 (CD163) markers by flowcytometry, their soluble forms (sCD16 and sCD163), and the serum levels of IL-10, IL-12, TGF-ß, and TNF-α cytokines using ELISA method, among 30 CD patients and 30 sex- and age-matched healthy subjects (HS). We also analyzed the diagnostic values of all variables with significant differences. RESULTS: CD14+CD163+ monocytes were more frequent in CD patients than HS, while CD14+CD16+ monocytes were higher in HS. IL-10and TNF-α increased, and TGF-ß expression was decreased among CD patients. The sCD16 serum levels were elevated in patients, while sCD163 was higher but not significant among CD patients. CD163+/CD16+ and IL-10/IL-12 ratios were higher in CD patients, and TGFß/TNFα ratio was higher in HS group. IL-10, CD14+CD163+, TNF-α, and IL-10/IL-12 ratios with the AUC over 0.7 were introduced as fair diagnostic markers. Our findings revealed that the M2 (CD14+CD163+) monocytes were more frequent among CD patients, and the cytokine balance was disturbed. CONCLUSION: According to the significant functional diversities of monocyte subtypes between CD patients and HS group, these immunologic markers could be introduced as specific diagnostic biomarkers for CD.

Frequency of auto-antibodies of type 1 diabetes in adult patients with celiac disease.

Both celiac disease (CD) and type 1 diabetes (T1D) are autoimmune diseases resulting from a complex interplay between genetic susceptibility and environmental factors. AIM: In this retrospective study, we determined the frequency of auto-antibodies of T1D in adult patients with active CD. MATERIALS AND METHODS: Eighty adult patients with active CD were included in our study. Ninety healthy blood donors (HBD) served as control group. Anti-glutamic acid decarboxylase IgG antibodies (GAD-Ab), anti-tyrosine phosphatase IgG antibodies (IA2-Ab), and anti-zinc transporter IgG antibodies (Zn-T8-Ab) were determined by enzyme-linked immunosorbent assay (ELISA) for patients and control group. For statistical analysis, we used Chi-square or Fisher's exact test. RESULTS: Out of 80 patients, 10 (12.50%) had auto-antibodies of T1D vs. only one in control group (1.11%) (p = 0.003). Simultaneous presence of GAD-Ab, IA2-Ab, and Zn-T8-Ab was found in one patient (1.25%). Nine patients had only GAD-Ab. IA2-Ab and Zn-T8-Ab were absent in all HBD. The frequency of GAD-Ab was significantly higher in CD patients than in HBD (12.5% vs 1.11%, p = 0.003). CONCLUSION: The present study has shown that CD is associated with a high frequency of auto-antibodies of T1D. Screening for T1D in this population, at risk for other autoimmune diseases, may be useful.

Nutritional Imbalances in Adult Celiac Patients Following a Gluten-Free Diet.

Celiac disease (CD) is a chronic autoimmune disorder of the small intestine, whose only effective treatment is a gluten-free diet (GFD). It is characterized by the atrophy of the intestinal villi that leads to altered nutrient absorption. This study describes the nutritional imbalances which may be found in adults with CD following a GFD. During the first year of treatment, deficiencies will overcome as the intestinal mucosa recovers. Thus, biochemical data will show this progression, together with the decrease in symptoms. In contrast, in the long term, when a strict GFD is followed and mucosal recovery is achieved, analyzing nutrient intake makes more sense. Macronutrient consumption is characterized by its low complex carbohydrate and fiber intakes, and high fat (especially SFA) and sugar intakes. This profile has been related to the consumption of GFP and their nutritional composition, in addition to unbalanced dietary habits. The most notable deficiencies in micronutrients are usually those of iron, calcium and magnesium and vitamin D, E and some of group B. It is necessary to follow up patients with CD and to promote nutritional education among them, since it could help not only to achieve a gluten free but also a balanced diet.

Coeliac disease enteropathy and symptoms may be aggravated by angiotensin receptor blockers in patients on a gluten-free diet.

BACKGROUND: Angiotensin receptor blocker-associated enteropathy (ARB-e) is an increasingly recognised clinical entity with symptoms and histological findings identical to coeliac disease (CD). There is evidence to suggest immune-mediated mucosal injury in ARB-e with a high prevalence of DQ2/DQ8; however, as IgA anti-tissue transglutaminase (anti-TTG) is usually negative, an insult other than TTG-mediated injury is suspected. The impact of ARBs on disease activity in patients with CD is not known. OBJECTIVE: To assess the effect of ARB exposure on patients with established CD. METHODS: A patient record search of 1142 individual patients attending a dedicated coeliac clinic from 2010 to the present identified 59 patients treated with ARB. Those with CD confirmed by serology (TTG + ve/EMA + ve) and histopathology (Marsh criteria) were included (n = 40, 0.52%). Data collected included disease duration, compliance with gluten-free diet (GFD), reported symptoms (diarrhoea, weight loss and abdominal pain), surrogate markers of absorption (Vitamin D, Iron, Calcium and Haemoglobin), in addition to anti-TTG titre and histological grade at last follow up. Patients were age and sex-matched in a 1:2 ratio with CD patients not taking ARBs (controls), with comparable rates of disease duration and compliance with GFD. RESULTS: The ARB and control groups were matched in terms of age (mean 66.2 years) and gender (female 63%). Strict compliance with GFD was reported in 55% and 56%, respectively. Persistent symptoms were reported in 10/40 (25%) of the ARB group compared with 7/82 (9%) of controls (p = 0.0181). There were lower rates of mucosal healing (Marsh grade 0) in the ARB group (36% n = 11) compared to controls (55%, n = 33). There was no significant difference in anti-TTG titres. Surrogate markers of absorption were comparable across the groups, except for Vitamin D which was lower in those taking olmesartan (p = 0.0015). CONCLUSIONS: ARBs may aggravate the enteropathy and lead to increased symptoms in patients with bone fide diagnosed CD following a GFD.

Iron Deficiency Anemia in Celiac Disease.

The iron absorption process developsmainly in the proximal duodenum. This portion of the intestine is typically destroyed in celiac disease (CD), resulting in a reduction in absorption of iron and subsequent iron deficiency anemia (IDA). In fact, the most frequent extra-intestinal manifestation (EIM) of CD is IDA, with a prevalence between 12 and 82% (in relation with the various reports) in patients with new CD diagnosis. The primary treatment of CD is the gluten-free diet (GFD), which is associated with adequate management of IDA, if present. Iron replacement treatment historically has been based on oral products containing ferrous sulphate (FS). However, the absorption of FS is limited in patients with active CD and unpredictable in patients on a GFD. Furthermore, a poor tolerability of this kind of ferrous is particularly frequent in patients with CD or with other inflammatory bowel diseases. Normalization from anemic state typically occurs after at least 6 months of GFD, but the process can take up to 2 years for iron stores to replenish.

Neurological Evaluation of Patients with Newly Diagnosed Coeliac Disease Presenting to Gastroenterologists: A 7-Year Follow-Up Study.

We have previously shown that 67% of patients with newly diagnosed coeliac disease (CD) presenting to gastroenterologists have evidence of neurological dysfunction. This manifested with headache and loss of co-ordination. Furthermore 60% of these patients had abnormal brain imaging. In this follow-up study, we re-examined and re-scanned 30 patients from the original cohort of 100, seven years later. There was significant reduction in the prevalence of headaches (47% to 20%) but an increase in the prevalence of incoordination (27% to 47%). Although those patients with coordination problems at baseline reported improvement on the gluten free diet (GFD), there were 7 patients reporting incoordination not present at baseline. All 7 patients had positive serology for one or more gluten-sensitivity related antibodies at follow-up. In total, 50% of the whole follow-up cohort were positive for one or more gluten-related antibodies. A comparison between the baseline and follow-up brain imaging showed a greater rate of cerebellar grey matter atrophy in the antibody positive group compared to the antibody negative group. Patients with CD who do not adhere to a strict GFD and are serological positive are at risk of developing ataxia, and have a significantly higher rate of cerebellar atrophy when compared to patients with negative serology. This highlights the importance of regular review and close monitoring.