Malignancy in adult celiac disease

Prior studies have suggested that the incidence of some neoplastic disorders, particularly malignant lymphoma and small intestinal adenocarcinoma, are increased in celiac disease. Earlier studies from the United Kingdom have also suggested a link between celiac disease and esophageal carcinoma, although this has not been confirmed in North America. The risk oF other gastrointestinal cancers seems to be limited. Gastric cancer does not appear to be detected more frequently, although direct endoscopic visualization of the upper gastrointestinal tract is now very common in patients with celiac disease. Colon cancer also appears to be limited in celiac disease, even in patients first diagnosed with celiac disease late in life. This has led to the hypothesis that untreated celiac disease may be protective, possibly owing to impaired absorption of fat or fat-soluble agents, including hydrocarbons and putative co-carcinogens implicated in the pathogenesis of colon cancer, which may be poorly absorbed and rapidly excreted.     

Narrow band imaging combined with water immersion technique in the diagnosis of celiac disease

BackgroundThe “multiple-biopsy” approach both in duodenum and bulb is the best strategy to confirm the diagnosis of celiac disease; however, this increases the invasiveness of the procedure itself and is time-consuming.AimTo evaluate the diagnostic yield of a single biopsy guided by narrow-band imaging combined with water immersion technique in paediatric patients.MethodsProspective assessment of the diagnostic accuracy of narrow-band imaging/water immersion technique-driven biopsy approach versus standard protocol in suspected celiac disease.ResultsThe experimental approach correctly diagnosed 35/40 children with celiac disease, with an overall diagnostic sensitivity of 87.5% (95% CI: 77.3–97.7). An altered pattern of narrow-band imaging/water immersion technique endoscopic visualization was significantly associated with villous atrophy at guided biopsy (Spearman Rho 0.637, p < 0.001). Concordance of narrow-band imaging/water immersion technique endoscopic assessments was high between two operators (K: 0.884). The experimental protocol was highly timesaving compared to the standard protocol.ConclusionsAn altered narrow-band imaging/water immersion technique pattern coupled with high anti-transglutaminase antibodies could allow a single guided biopsy to diagnose celiac disease. When no altered mucosal pattern is visible even by narrow-band imaging/water immersion technique, multiple bulbar and duodenal biopsies should be obtained.     

Presentations of adult celiac disease in a nationwide patient support group

Recent epidemiological studies primarily from Europe document that adult celiac disease often lacks the classic presentation of steatorrhea and weight loss. There are few surveys of adult celiac disease in the United States. We surveyed the large population of a nationwide patient support group to determine their disease presentations. In the initial survey (N = 1032 respondents), the median age at onset was 46 years, and the diagnosis of adult celiac disease was often delayed (median 12 months, with 21% delayed over 10 years). Only 32% of adults were underweight, and only about 50% reported frequent diarrhea and weight loss. A second survey documented that common presenting symptoms were fatigue (82%), abdominal pain (77%), bloating or gas (73%), and anemia (63%). Initial physician diagnoses were often irritable bowel syndrome (37%), psychological disorders (29%), and fibromyalgia (9%). These initial presentations are similar to those in Europe and often resemble irritable bowel syndrome.     

乳糜泻临床研究进展

乳糜泻(celiac disease,CD)是患者对麸质不耐受引起小肠黏膜病变为特征的一种原发性吸收不良综合征.当遗传易感者食用含有麸质的食物后,引起机体的免疫应答,破坏小肠绒毛,引起小肠吸收不良.依据吸收不良的程度,CD的症状有个体差异,有的无症状或症状轻微,有的症状较重.典型表现为腹泻、腹痛、腹胀等消化系症状,也有的患者出现消化系外症状.血清标志物检测和小肠活检组织病理可明确诊断.此病在北美、北欧、澳大利亚发病率较高,在我国报道少见.本文就CD的流行病学、发病机制、临床表现以及诊断和治疗作一综述.     

Genetics and celiac disease: the importance of screening

The prevalence of celiac disease (CD) is increasing. Despite an increased awareness and an improvement in diagnostic testing, the majority of individuals with CD remain undiagnosed. Currently, genetic testing in screening for CD is used only to exclude a diagnosis or reinforce a strong clinical suspicion. In this paper, we review the most current literature regarding genetic testing in CD. In response to important data revealing that an individual’s HLA haplotype is one of the strongest known predictors of CD, we propose genetic screening for at-risk infants to stratify individuals based on genetic risk to ultimately create genetic specific screening algorithms.     

Non-dietary forms of treatment for adult celiac disease

At present, treatment for celiac disease includes a strict gluten-free diet. Compliance, however, is difficult and gluten-free food products are costly, and, sometimes very inconvenient. A number of potential alternative measures have been proposed to either replace or supplement gluten-free diet therapy. In the past, non-dietary forms of treatment were used (e.g., corticosteroids) by some clinicians, often to supplement a gluten-free diet in patients that appeared to be poorly responsive to a gluten-free diet. Some of new and novel non-dietary measures have already advanced to a clinical trial phase. There are still some difficulties even if initial studies suggest a particularly exciting and novel form of non-dietary treatment. In particular, precise monitoring of the response to these agents will become critical. Symptom or laboratory improvement may be important, but it will be critical to ensure that ongoing inflammatory change and mucosal injury are not present. Therapeutic trials will be made more difficult because there is already an effective treatment regimen.     

Prevalence of celiac disease in an urban area of Brazil with predominantly European ancestry

INTRODUCTIONCeliac disease(CD)is a chronic disease that affects genetically susceptible individuals and is characterized by permanent intolerance to gluten and other related proteins,causing nonspecific,characteristic lesions in the small bowel mucosa[1].…     

Age-related differences in celiac disease: Specific characteristics of adult presentation

Celiac disease may appear both in early childhood andin elderly subjects. Current knowledge of the disease has revealed some differences associated to the age of presentation. Furthermore, monitoring and prognosis of celiac subjects can vary depending on the pediatric or adult stage. The main objective of this review is to provide guidance for the adult diagnostic and follow-up processes, which must be tailored specifically for adults and be different from pediatric patients.     

Potential celiac disease in type 1 diabetes: a multicenter study

Aims

To describe the prevalence of potential celiac disease (pot-CD) in young patients with type 1 diabetes mellitus (T1DM) and characterize their clinical features.

Methods

This cross-sectional multicenter study involved 8717 T1DM patients from 31 Italian centers. Information was collected on the total number of T1DM patients, CD patients and pot-CD patients. The following data were collected on pot-CD patients: gender, age at T1DM diagnosis, age at the first CD serological positivity, presence of CD-related symptoms, presence of other autoimmune disorders and treatment with gluten free diet (GFD). One thousand-three-hundred-sixty-one patients who were positive for CD serology were the control group.

Results

CD serological positivity was found in 7.2% T1DM patients. Prevalence of pot-CD was 12.2% (n = 77) among CD positive patients: symptoms were present in 12/77; a third autoimmune disorder was found in 15 patients. Prevalence of pot-CD in the control population was 8.4% (n = 114; p = 0.005). No difference was found with regard to clinical features. Only few symptomatic patients were on GFD both in T1DM and control patients.

Conclusions

A higher prevalence of pot-CD was found in T1DM patients, that may be ascribed to the routine screening, although the influence of genetic factors cannot be excluded.     

Changing presentation of adult celiac disease

The mode of presentation of celiac disease in the United States is not known. We investigated the demographic and clinical features of 227 patients with biopsy-proven celiac disease and determined if there had been changes over time. The patients had been entered into a database; those seen prior to 1990 were retrospectively entered while those seen subsequently were prospectively entered. A symptomatic presentation described the classical presentation of celiac disease with prominent gastrointestinal symptoms: diarrhea and weight loss. Females were younger and had a longer duration of symptoms compared to males. The modes of presentation were symptomatic (62%), anemia or reduced bone density (15%), screening first-degree relatives (13%), and incidental diagnosis at endoscopy (8%). We compared those diagnosed before and after 1993 (when serologic testing was first used), and noted a reduction in those presenting with diarrhea, 73% vs 43% (P = 0.0001) and a reduction in the duration of symptoms, from 9.0 ± 1.1 years to 4.4 ± 0.6 years (P < 0001). In conclusion, the percentage of celiac disease patients presenting with diarrhea has decreased, probably related to the more widespread use of serologic testing for celiac disease.     

Usefulness of duodenal biopsy during routine upper gastrointestinal endoscopy for diagnosis of celiac disease

AIM: To describe the trend in duodenal biopsy performance during routine upper gastrointestinal endoscopy in an adult Spanish population, and to analyze its value for the diagnosis of celiac disease in clinical practice. METHODS: A 15 year-trend (1990 to 2004) in duodenal biopsy performed when undertaking upper gastrointestinal endoscopy was studied. We analysed the prevalence of celiac disease in the overall group, and in the subgroups with anaemia and/or chronic diarrhoea. RESULTS: Duodenal biopsy was performed in 1033 of 13 678 upper gastrointestinal endoscopies (7.6%); an increase in the use of such was observed over the study period (1.9% in 1990-1994, 5% in 1995-1999 and 12.8% in 2000-2004). Celiac disease was diagnosed in 22 patients (2.2%), this being more frequent in women than in men (3% and 1% respectively). Fourteen out of 514 (2.7%) patients with anaemia, 12 out of 141 (8.5%) with chronic diarrhoea and 8 out of 42 (19%) with anaemia plus chronic diarrhoea had celiac disease. A classical clinical presentation was observed in 55% of the cases, 23% of the patients had associated dermatitis herpetiformis and 64% presented anaemia; 9% were diagnosed by familial screening and 5% by cryptogenetic hypertransaminasaemia. CONCLUSION: Duodenal biopsy undertaken during routine upper gastrointestinal endoscopy in adults, has been gradually incorporated into clinical practice, and is a useful tool for the diagnosis of celiac disease in high risk groups such as those with anaemia and/or chronic diarrhoea.     

Enteroscopy for the early detection of small bowel tumours in at-risk celiac patients

BackgroundA subset of celiac patients shows a high risk for small bowel malignancies.AimsTo select celiac patients considered at risk and evaluate the diagnostic yield of enteroscopy in this context.MethodsCeliac patients were enrolled from a tertiary referral centre during the period June 2011–June 2013, based on the following criteria: (i) patients diagnosed when aged 50+ and with poor response to gluten-free dieting; (ii) low dietary compliance; (iii) alarm symptoms. The patients underwent small bowel capsule endoscopy and/or double-balloon enteroscopy. Control populations were represented by the 165 non-celiac patients undergoing capsule endoscopy for obscure gastrointestinal bleeding, and the 815,362-strong population of the Italian province of Varese as a registered cohort.ResultsFifty-three patients (19% males, mean age 43.6 ± 17.4 years) were evaluated. Two jejunal adenocarcinomas and one ileal neuro-endocrine tumour were diagnosed by enteroscopy (the diagnostic yield for malignancies in the selected population being 5.7%). In the non-celiac controls the detection rate of small bowel tumours by capsule endoscopy was 0.6% (P = 0.04). When compared to the registered population, the relative risk for intestinal malignancy was 1282 (95% CI, 407–4033; P < 0.0001).ConclusionsCapsule endoscopy and double-balloon enteroscopy can be considered for early disease management of a subset of celiac patients.     

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.     

Co‐occurrence of eosinophilic esophagitis and potential/probable celiac disease in an adult cohort: a possible association with implications for clinical practice

We describe an adult cohort with eosinophilic esophagitis (EoE) and evidence of celiac disease (CD), propose a change in diagnostic practice to better characterize these conditions, and hypothesize new directions for research. Pediatric studies postulate association between gluten sensitivity and EoE. However, few publications describe the prevalence, detection, or therapeutic and pathophysiologic implications of such association in adults. Retrospective chart review was done on patients diagnosed with EoE from 2009 to 2010 at University of Utah Hospitals and Clinics. Data included sex, age, presentation, duodenal pathology, tissue transglutaminase immunoglobulin A antibody (TTG) positivity, human leukocyte antigen (HLA) type (when indicated), and gross and microscopic Esophagogastroduodenoscopy (EGD) findings. Duodenal biopsy, TTG results, and HLA type were correlated. Endoscopy was repeated after gluten‐free diet. Forty‐four of 75 patients were followed in EoE specialty clinic with duodenal biopsy and TTG testing per protocol. Six EoE patients had potential or probable CD. No sex or age differences were noted between those with findings of CD and EoE and those with EoE alone. Six patients with findings of CD and EoE followed gluten‐free diet. Five underwent repeat endoscopy. Three had resolution of esophageal eosinophilia. Potential or probable CD was commonly found in adults with EoE. Diagnosis of CD may be challenging due to nonspecific symptoms and insufficient duodenal biopsy and serologic testing. Furthermore, gluten‐free diet resolved EoE findings in some patients, suggesting possible shared pathophysiology in some cases of EoE and CD. TTG testing and adequate duodenal biopsy may further direct clinical care for EoE patients, and studies are needed to elucidate mechanisms linking EoE and CD.     

Population screening for celiac disease: follow up of patients identified by positive serology

BACKGROUND AND AIM: A previous study that evaluated the prevalence of celiac disease (CD) in a cohort of healthy blood donors, found that 3.8% of subjects had positive serology for CD. The aim of the present study was to examine how the screening results and the diagnosis of CD affected these patients' lifestyle and attitude toward CD. METHODS: All subjects with positive serology for CD (n = 59) found in the previous study of healthy blood donors (n = 1571) were contacted and interviewed. Data collected included current and previous symptoms compatible with CD, medical follow up since being informed of positive serology for CD and adherence to gluten-free diet (GFD). Information was obtained regarding attitude towards the screening for CD, the results of the screening, and the effect of screening on subjects' lifestyle. RESULTS: Of the 59 subjects, 51 were available for telephone interview, including all 10 subjects diagnosed with CD (positive serology and biopsy), 17/20 with positive serology and normal intestinal mucosa, and 24/29 with positive serology who refused to undergo intestinal biopsy. Of the 10 patients diagnosed with CD, four adhere to GFD. Only 1/17 subjects with normal intestinal mucosa repeated serology. Two of the 24 who initially refused a biopsy, underwent an intestinal biopsy, and one of them was currently diagnosed with CD. Only one patient diagnosed with CD had all his family members screened for CD. CONCLUSIONS: The data suggest that many of the patients identified in this screened population do not ultimately benefit from the purpose of the screening, which was early identification and treatment of a common disease with potential serious consequences.     

中国湖北地区腹泻型肠易激综合征患者中成人乳糜泻血清学筛查

 目的 筛查伴有血清学特征的成人乳糜泻在中国湖北人群特别是腹泻型肠易激综合征（D-IBS）患者中的患病情况。 
方法 依据罗马Ⅲ标准选取282例D-IBS患者,并以296例年龄和性别匹配并且无腹泻症状的体检人群作为对照组,采用ELISA法检测血清IgA/IgG型抗人组织转谷氨酰胺酶/脱酰胺麸朊肽抗体（抗htTG/DGP）水平。血清抗体阳性者建议行去麸质饮食治疗5~6个月,观察临床疗效,并复查血清中抗htTG/DGP水平。
结果 纳入试验的578例研究对象中,血清抗htTG/DGP阳性7例,其中D-IBS组5例（5/282, 1.77%）,对照组2例（2/296, 0.68%）。抗htTG/DGP阳性研究对象中,4例同意并进行了平均5.2个月的去麸质饮食治疗,随访观察显示其临床症状均得到明显改善,并伴随血清抗htTG/DGP水平降低。
结论 乳糜泻在中国可能并非罕见疾病,特别是在D-IBS患者乳糜泻发病率更高,因此,在IBS患者中进行乳糜泻血清学筛查具有重要意义。     

Prevalence of celiac disease in adult patients with refractory functional dyspepsia： Value of routine duodenal biopsy

AIM： To investigate the prevalence of celiac disease （CD） in adult patients referred to an open access gastroenterology clinic in the south of Italy and submitted to esophago-gastro-duodenoscopy （EGD） for evaluation of refractory functional dyspepsia. METHODS： Seven hundred and twenty six consecutive dyspeptic patients （282 male, 444 female; mean age 39.6 years, range 18-75 years） with unexplained prolonged dyspepsia were prospectively enrolled. Duodenal biopsies were taken and processed by standard staining. Histological evaluation was carried out according to the Marsh-Oberhuber criteria. RESULTS： The endoscopic findings were： normal in 61.2%, peptic lesions in 20.5%, malignancies in 0.5%, miscellaneous in 16.7%. CD was endoscopically diagnosed in 8 patients （1.1%）, histologically in 15 patients （2%）. The endoscopic features alone showed a sensitivity of 34.8% and specificity of 100%, with a positive predictive value （PPV） of 100% and a negative predictive value （NPP） of 97.9%. CONCLUSION： This prospective study showed that CD has a high prevalence （1：48） in adult dyspeptic patients and suggests the routine use of duodenal biopsy in this type of patient undergoing EGD.     

Familial prevalence among first-degree relatives of celiac disease in North India

BACKGROUND AND OBJECTIVES: Prevalence of celiac disease is increased in first-degree relatives with reported prevalence rates in the west between 2.8 and 10%. Paucity of similar data from Asia and the Indian subcontinent prompted us to determine the familial prevalence of celiac disease in first-degree relatives of patients diagnosed with this disorder in Northern India. METHODS: One hundred sixty-nine first-degree relatives (66 parents, 71 siblings and 32 children) of 53 probands were screened by using anti tissue transglutaminase antibodies. Duodenal biopsy was performed in all seropositive relatives and graded as per Marsh classification. Patients with both positive serology and biopsy suggestive of celiac disease were classified as typical celiac disease whereas those with only positive serology were classified as potential celiacs. RESULTS: The prevalence of celiac disease among first-degree relatives was 8.2% (14/169). The prevalence of celiac disease among siblings (15.6%) was much higher as compared to that in parents (3.5%) and offspring (3%). More than one family member was affected in 23% (12/53) of families. Of 14 new cases detected by targeted screening, 11 (78%) were overtly symptomatic with either chronic diarrhoea (8) or easy fatiguability (3). Growth retardation was seen in all six newly diagnosed children, three of whom (22%) were otherwise asymptomatic. Eight members detected to be seropositive had minimal changes on duodenal biopsy (Marsh I and II) suggesting that they have potential celiac disease. CONCLUSION: Familial prevalence of celiac disease in North India is similar to the data from the West. However unlike the situation in the West, the overwhelming majority of first-degree relatives in India are overtly symptomatic with majority having chronic diarrhoea. Since gluten restriction is a highly effective treatment modality, early detection of these patients would result in significant improvement in quality of life as manifested by cessation of diarrhoea and improvement in growth and lab parameters. Our data strongly supports the targeted screening of all first-degree relatives of celiac disease patients in north India.