Peter H. R. Green

Extraintestinal manifestations of coeliac disease

Coeliac disease is a common disorder that can arise at any age and typically presents with a broad spectrum of symptoms. The disease is thought to be underdiagnosed, in part owing to the fact that coeliac disease is often characterized by associated conditions and extraintestinal manifestations that can misdirect and impede diagnosis. Some of these manifestations are direct consequences of autoimmunity, such as dermatitis herpetiformis or gluten ataxia, whereas others are indirectly related to inflammation and/or malabsorption including anaemia, osteoporosis, short stature and delayed puberty. Any organ from the central nervous system to joints, liver or teeth can be affected. In some cases, extraintestinal symptoms are the only clinical manifestations of coeliac disease or occur in conjunction with diarrhoea and malabsorptive symptoms. An increased awareness among medical practitioners of the variety of extraintestinal manifestations of coeliac disease is essential to improve diagnosis and treatment.

The coeliac stomach: gastritis in patients with coeliac disease.

Lymphocytic gastritis (LG) is an uncommon entity with varying symptoms and endoscopic appearances. This condition, as well as two forms of H. pylori‐negative gastritis [chronic active gastritis (CAG) and chronic inactive gastritis (CIG)], appears to be more common in patients with coeliac disease (CD) based on single‐centred studies.

Ethnic Variations in Duodenal Villous Atrophy Consistent With Celiac Disease in the United States.

BACKGROUND & AIMSnCeliac disease is a common disorder with a worldwide distribution, although the prevalence among different ethnicities varies. We aimed to measure the prevalence of duodenal villous atrophy among patients of different ethnicities throughout the United States.nnnMETHODSnWe performed a cross-sectional study of all patients who had duodenal biopsies submitted to a national pathology laboratory between January 2, 2008 and April 30, 2015. The prevalence of villous atrophy was calculated for the following ethnicities by using a previously published algorithm based on patient names: North Indian, South Indian, East Asian, Hispanic, Middle Eastern, Jewish, and other Americans.nnnRESULTSnAmong all patients (nxa0= 454,885), the median age was 53 years, and 66% were female. The overall prevalence of celiac disease was 1.74%. Compared with other Americans (nxa0= 380,163; celiac disease prevalence, 1.83%), celiac disease prevalence was lower in patients of South Indian (nxa0= 177, 0%; Pxa0= .08), East Asian (nxa0= 4700, 0.15%; P ≤ .0001), and Hispanic (nxa0= 31,491, 1.06%; P ≤ .0001) ethnicities. Celiac disease was more common in patients from the Punjab region (nxa0= 617, 3.08%) than in patients from North India (nxa0= 1195, 1.51%; Pxa0= .02). The prevalence of celiac disease among patients of Jewish (nxa0= 17,806, 1.80%; Pxa0= .78) and Middle Eastern (nxa0= 1903, 1.52%; Pxa0= .33) ethnicities was similar to that of other Americans. Among Jewish individuals (nxa0= 17,806), the prevalence of celiac disease was 1.83% in Ashkenazi persons (nxa0= 16,440) and 1.39% in Sephardic persons (nxa0= 1366; Pxa0= .24).nnnCONCLUSIONSnAmong patients undergoing duodenal biopsy, individuals from the Punjab region of India constitute the ethnic group in the United States with the highest prevalence of villous atrophy consistent with celiac disease. Compared with other Americans, villous atrophy prevalence on duodenal biopsy is significantly lower among U.S. residents of South Indian, East Asian, and Hispanic ancestry.

Transition from childhood to adulthood in coeliac disease: the Prague consensus report

The process of transition from childhood to adulthood is characterised by physical, mental and psychosocial development. Data on the transition and transfer of care in adolescents/young adults with coeliac disease (CD) are scarce. In this paper, 17 physicians from 10 countries (Sweden, Italy, the USA, Germany, Norway, the Netherlands, Australia, Britain, Israel and Denmark) and two representatives from patient organisations (Association of European Coeliac Societies and the US Celiac Disease Foundation) examined the literature on transition from childhood to adulthood in CD. Medline (Ovid) and EMBASE were searched between 1900 and September 2015. Evidence in retrieved reports was evaluated using the Grading of Recommendation Assessment, Development and Evaluation method. The current consensus report aims to help healthcare personnel manage CD in the adolescent and young adult and provide optimal care and transition into adult healthcare for patients with this disease. In adolescence, patients with CD should gradually assume exclusive responsibility for their care, although parental support is still important. Dietary adherence and consequences of non-adherence should be discussed during transition. In most adolescents and young adults, routine small intestinal biopsy is not needed to reconfirm a childhood diagnosis of CD based on European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) or North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) criteria, but a biopsy may be considered where paediatric diagnostic criteria have not been fulfilled, such as, in a patient without biopsy at diagnosis, additional serology (endomysium antibody) has not been performed to confirm 10-fold positivity of tissue transglutaminase antibodies or when a no biopsy strategy has been adopted in an asymptomatic child.

Endoscopic biopsy technique in the diagnosis of celiac disease: one bite or two?

BACKGROUNDnThe diagnosis of celiac disease is dependent on the quality of biopsy specimens obtained at EGD. Endoscopists may obtain a single- or double-biopsy specimen with each pass of the forceps.nnnOBJECTIVEnTo compare the quality of biopsy specimens obtained with the single-biopsy and double-biopsy techniques.nnnDESIGNnProspective cohort study.nnnSETTINGnU.S. tertiary-care university hospital.nnnPATIENTSnPatients undergoing upper endoscopy with confirmed, suspected, or unknown celiac disease status.nnnINTERVENTIONSnFour biopsy specimens from the second portion of the duodenum: 2 by using the single-biopsy technique (1 bite per pass of the forceps) and an additional 2 by using the double-biopsy technique (2 bites per pass of the forceps). Specimens were blindly reviewed to determine orientation, consecutive crypt-to-villous units, and Marsh score.nnnMAIN OUTCOME MEASUREMENTSnProportion of well-oriented biopsy specimens.nnnRESULTSnPatients (N = 86) were enrolled, 47% with known celiac disease, 36% with suspected celiac disease, and 17% with an unknown celiac disease status. Well-oriented biopsy specimens were noted in 66% of patients with the single-biopsy technique and 42% of patients with the double-biopsy technique (P < .01). Analysis of matched pairs showed improved orientation with the single-biopsy technique (odds ratio 3.1; 95% confidence interval, 1.5-7.1; P < .01). This persisted in subgroup analysis of patients with known celiac disease (P = .02), villous atrophy (P = .02), and a final diagnosis of celiac disease (P < .01).nnnLIMITATIONSnA single-center trial.nnnCONCLUSIONnThe single-biopsy technique improves the yield of well-oriented duodenal biopsy specimens. Endoscopists should consider taking only 1 biopsy specimen per pass of the forceps in patients undergoing biopsies of the duodenal mucosa.

Prevalence of Celiac Disease in Patients with Autoimmune Thyroid Disease: A Meta-Analysis

BACKGROUNDnSeveral screening studies have indicated an increased prevalence of celiac disease (CD) among individuals with autoimmune thyroid disease (ATD), but estimates have varied substantially.nnnOBJECTIVEnThe aim of this study was to examine the prevalence of CD in patients with ATD.nnnMETHODnA systematic review was conducted of articles published in PubMed Medline or EMBASE until September 2015. Non-English papers with English-language abstracts were also included, as were research abstracts without full text available when relevant data were included in the abstract. Search terms included celiac disease combined with hypothyroidism or hyperthyroidism or thyroid disease. Fixed-effects inverse variance-weighted models were used. Meta-regression was used to examine heterogeneity in subgroups.nnnRESULTSnA pooled analysis, based on 6024 ATD patients, found a prevalence of biopsy-confirmed CD of 1.6% [confidence interval (CI) 1.3-1.9%]. Heterogeneity was large (I(2)u2009=u200970.7%). The prevalence was higher in children with ATD (6.2% [CI 4.0-8.4%]) than it was in adults (2.7%) or in studies examining both adults and children (1.0%). CD was also more prevalent in hyperthyroidism (2.6% [CI 0.7-4.4%]) than it was in hypothyroidism (1.4% [CI 1.0-1.9%]).nnnCONCLUSIONSnAbout 1/62 patients with ATD have biopsy-verified CD. It is argued that patients with ATD should be screened for CD, given this increased prevalence.

Partner Burden: A Common Entity in Celiac Disease

BackgroundCaregiver burden is documented in several chronic diseases, but it has not been investigated in celiac disease (CD).AimsWe aim to quantify the burden to partners of CD patients and identify factors that affect the perceived burden.Methods We surveyed patients with biopsy-proven CD and their partners. Patients completed CD-specific questions, including the validated Celiac Symptom Index (CSI) survey. Partners completed the validated Zarit Burden Interview (ZBI) and questions regarding sexual and relationship satisfaction. Univariable and multivariable analyses were used to assess the association between demographics, CD characteristics, and partner burden.ResultsIn total, 94 patient/partner pairs were studied. Fifteen patients (16xa0%) reported a CSI score associated with a poor quality of life, and 34 partners (37xa0%) reported a ZBI score corresponding to mild-to-moderate burden. Twenty-two partners (23xa0%) reported moderate-to-low overall relationship satisfaction, and 12 (14xa0%) reported moderate-to-low sexual satisfaction. The degree of partner burden was directly correlated with patient CSI score (rxa0=xa00.27; pxa0=xa00.008), and there were moderate-to-strong inverse relationships between partners’ burden and relationship quality (rxa0=xa0−0.70; pxa0<xa00.001) and sexual satisfaction (rxa0=xa0−0.42; pxa0<xa00.001). On multivariable logistic regression, predictors of mild-to-moderate partner burden were low partner relationship satisfaction (OR 17.06, 95xa0% CI 2.88–101.09, pxa0=xa00.002) and relationship duration ≥10xa0years (OR 14.42, 95xa0% CI 1.69–123.84, pxa0=xa00.02).ConclusionsPartner burden is common in CD, with more than one-third of partners experiencing mild-to-moderate burden. Partner burden is directly correlated with patient symptom severity, and it increases with poorer sexual and relationship satisfaction. Healthcare providers should address relationship factors in their care of patients with CD.

Risk of Dementia in Patients with Celiac Disease: A Population-Based Cohort Study

BACKGROUNDnPatients with celiac disease (CD) frequently report cognitive symptoms when they are exposed to gluten, and cognitive deficits have been quantified in patients with newly diagnosed CD.nnnOBJECTIVEnTo determine whether patients with CD have an increased risk of dementia.nnnMETHODSnUsing a population-based database of older adults (age ≥50 years) with histologically proven CD (duodenal/jejunal villous atrophy) from all 28 pathology departments in Sweden, we compared the incidence of a subsequent dementia diagnosis to those of age- and gender-matched controls.nnnRESULTSnAmong patients with CD (nu200a=u200a8,846) and controls (nu200a=u200a43,474), the median age was 63 years and 56% were female. During a median follow-up time of 8.4 years, dementia was diagnosed in 4.3% of CD patients and 4.4% of controls (HR 1.07; 95% CI 0.95-1.20). Although there was an increased risk of dementia in the first year following a diagnosis of CD (HR 1.73; 95% CI 1.15-2.61), this risk was not present in the whole observation period. Among those subjects with a dementia subtype specified, the increased risk was restricted to vascular dementia (HR 1.28; 95% CI 1.00-1.64) and was not present for Alzheimers dementia (HR 1.12; 95% CI 0.91-1.37).nnnCONCLUSIONSnPatients with CD are not at increased risk for dementia overall, though subgroup analysis suggests that they may be at increased risk for vascular dementia.

Amount May Beat Timing: Gluten Intake and Risk of Childhood Celiac Disease

In the current issue of Clinical Gastroenterology and Hepatology, Aronsson et al from The Environmental Determinants of Diabetes in the Young (TEDDY) study group explore the relationship between gluten intake and risk of celiac disease (CD) in genetically atrisk children. Although the data in this nested casecontrol study originated from Sweden where the rate of CD is highest, the TEDDY study group has its scientific center in Florida, and a novel by one of that state’s most famous authors may serve as an introduction to this article. In Ernest Hemingway’s book The Sun Also Rises, two of the main characters, Bill and Mike, discuss financial matters, and Bill asks: “How did you go bankrupt?”, and Mike answers, “Two ways. Gradually, then suddenly.” This article shows that even if you introduce gluten gradually into an infant’s diet, the child can still develop CD suddenly. Children with early diagnosed CD had a lower gluten consumption at 6 months of age than controls (albeit nonsignificant), but children with CD consumed larger amounts of gluten later at the age of 1–2 years than genetically predisposed children who did not subsequently develop the disease. Because of the abundant previous literature on infant feeding and other risk factors, what does this article add? It actually adds a lot. In recent years, prospective cohort studies and 2 randomized clinical trials have shown that age at gluten introduction and breastfeeding duration may be less important for the risk of developing CD (at least in childhood) than previously thought. However, no earlier study has used prospectively collected data to investigate the range of gluten quantity in early infant nutrition and risk of CD. Aronsson et al analyzed a subset of the prospective cohort TEDDY study, matching 146 Swedish children with CD with 436 controls. The authors found that for each additional gram of gluten consumed per day before tissue transglutaminase seroconversion, the risk of future CD increased by 28%. They also found that

Recommendations to quantify villous atrophy in video capsule endoscopy images of celiac disease patients.

AIM To quantify the presence of villous atrophy in endoscopic images for improved automation. METHODS There are two main categories of quantitative descriptors helpful to detect villous atrophy: (1) Statistical and (2) Syntactic. Statistical descriptors measure the small intestinal substrate in endoscope-acquired images based on mathematical methods. Texture is the most commonly used statistical descriptor to quantify villous atrophy. Syntactic descriptors comprise a syntax, or set of rules, for analyzing and parsing the substrate into a set of objects with boundaries. The syntax is designed to identify and distinguish three-dimensional structures based on their shape. RESULTS The variance texture statistical descriptor is useful to describe the average variability in image gray level representing villous atrophy, but does not determine the range in variability and the spatial relationships between regions. Improved textural descriptors will incorporate these factors, so that areas with variability gradients and regions that are orientation dependent can be distinguished. The protrusion syntactic descriptor is useful to detect three-dimensional architectural components, but is limited to identifying objects of a certain shape. Improvement in this descriptor will require incorporating flexibility to the prototypical template, so that protrusions of any shape can be detected, measured, and distinguished. CONCLUSION Improved quantitative descriptors of villous atrophy are being developed, which will be useful in detecting subtle, varying patterns of villous atrophy in the small intestinal mucosa of suspected and known celiac disease patients.