Risk of malignancy in patients with celiac disease

PURPOSE: Studies from Europe have demonstrated an increased risk of malignancy, especially non-Hodgkin's lymphoma, in patients with celiac disease. However, there are no data on the risk for similar patients in the United States. Our aim was to estimate the risk of malignancy in a cohort of patients with celiac disease compared with the general U.S. population and to determine if a gluten-free diet is protective. METHODS: Patients with celiac disease seen between July 1981 and January 2000 at a referral center were included. Standardized morbidity ratios (SMRs) (ratio of observed to expected) and corresponding 95% confidence intervals (CI) were calculated, using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. RESULTS: Forty-three (11%) of 381 celiac disease patients had a diagnosis of cancer; 9 were after the diagnosis of celiac disease, 7 were simultaneous (during same month or admission), and 27 were before the diagnosis. The standardized morbidity ratio for all cancers combined was 1.5 (95% CI: 0.3 to 7.5), with significantly increased values for small bowel cancer (SMR = 34; 95% CI: 24 to 42), esophageal cancer (SMR = 12; 95% CI: 6.5 to 21), non-Hodgkin's lymphoma (SMR = 9.1; 95% CI: 4.7 to 13), and melanoma (SMR = 5.0; 95% CI: 2.1 to 12). Following the diagnosis of celiac disease, patients were at increased risk of non-Hodgkin's lymphoma only (SMR = 6.2; 95% CI: 2.9 to 14), despite adherence to a gluten-free diet. The non-Hodgkin's lymphoma included both T-cell and B-cell types and occurred in both gastrointestinal (n = 5) and extraintestinal sites (n = 4). CONCLUSION: In this cohort of patients with celiac disease, we observed increased risks of small intestinal adenocarcinoma, esophageal cancer, melanoma, and non-Hodgkin's lymphoma. The risk of non-Hodgkin's lymphoma persisted despite a gluten-free diet.     

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.     

Risk of fractures in celiac disease patients: a cross-sectional, case-control study

OBJECTIVES: Although osteopenia and osteoporosis are well-recognized complications of celiac disease, no controlled studies have been done to assess the prevalence of fractures in a large cohort of patients. The objectives of this study were to determine the prevalence of bone fractures and vertebral deformities in celiacs and to analyze the relationship between fractures and clinical data of patients. METHODS: We studied 165 patients with a well-established diagnosis of celiac disease. A similar number of age- and gender-matched control subjects with functional GI disorders were evaluated. The design of the study was cross-sectional, with a retrospective historical review through a personal interview of all subjects. All patients underwent bone mineral density measurement by dual-energy, x-ray absorptiometry and spinal x-ray. Vertebral deformities were determined by visual inspection of spinal x-rays and by morphometric analysis. RESULTS: Among celiacs, 41 patients (25%) referred have had from one to five fractures in the peripheral skeleton. On the contrary, only 14 (8%) control subjects experienced fractures. This difference was highly significant (odds ratio, 3.5; 95% confidence interval [CI], 1.8-7.2; p<0.0001). Although inspection of spinal x-rays showed evidence of vertebral deformities in the lumbar spine in only two patients, a more detailed examination of lateral x-rays using morphometric criteria detected lumbar spine vertebral deformities in nine (five also had fractures in the peripheral skeleton) and in four controls (odds ratio, 2.8; 95% CI, 0.7-11.5; p = NS). Eighty percent of fractures were detected before the diagnosis of celiac disease or in patients who were noncompliant with the gluten-free diet; only 7% of patients experienced fractures after starting treatment. Regression analysis adjusted for multiple comparisons showed that patients with fractures were diagnosed with celiac disease later (p<0.06) and remained undiagnosed for more prolonged periods (p<0.05). There was a trend, which did not reach statistical significance, for a lower bone mineral density in the lumbar spine and total skeleton among patients with fractures. CONCLUSIONS: This study has demonstrated that patients with celiac disease had a high prevalence of bone fractures in the peripheral skeleton. Most of these events occurred before diagnosis or while patients were noncompliant with gluten-containing diet. Our results suggest that early diagnosis and effective treatment of celiac disease were the most relevant measures to protect patients from the risk of fractures.     

Risk of primary adrenal insufficiency in patients with celiac disease

OBJECTIVES: Earlier research has suggested a positive association between Addison's disease (AD) and celiac disease (CD). We have here investigated the risk of AD in individuals with CD from a general population cohort. METHODS: Through the Swedish national registers we identified 14,366 individuals with a diagnosis of CD (1964-2003) and 70,095 reference individuals matched for age, sex, calendar year, and county of residence. We used Cox regression to estimate hazard ratios (HRs) for subsequent AD. Analyses were restricted to individuals with more than 1 yr of follow-up and without AD prior to study entry or within 1 yr after study entry. Conditional logistic regression estimated the odds ratio for CD in individuals with prior AD. RESULTS: There was a statistically significantly positive association between CD and subsequent AD [HR = 11.4; 95% confidence interval (CI) = 4.4-29.6]. This risk increase was seen in both children and adults and did not change with adjustment for diabetes mellitus or socioeconomic status. When we restricted reference individuals to inpatients, the adjusted HR for AD was 4.6 (95% CI = 1.9-11.4). Individuals with prior AD were at increased risk of CD (odds ratio = 8.6; 95% CI = 3.4-21.8). CONCLUSIONS: This study found a highly increased risk of AD in individuals with CD. This relationship was independent of temporal sequence. We therefore recommend that individuals with AD should be screened for CD. We also suggest an increased awareness of AD in individuals with CD.     

Risk factors associated with missed colorectal flat adenoma: A multicenter retrospective tandem colonoscopy study

AIM: To determine the miss rate for colorectal flat adenomas during colonoscopy and the risk factors. METHODS: Flat adenomas are frequently missed during colonoscopy. However, the risk factors that influence their miss rates are unclear. This was a multicenter, retrospective study in which patients diagnosed with colorectal adenomas at a diagnostic colonoscopy and followed within 3 mo by a second therapeutic colonoscopy were pooled out from the established database. The “per-patient” and “per-adenoma” adenoma miss rates (AMR) for overall adenomas and flat adenomas, and patient-, adenoma-, and procedure-related risk factors potentially associated with the “per-adenoma” AMR for flat adenomas were determined. RESULTS: Chromoscopy and high-definition colonoscopy were not taken under consideration in the study. Among 2093 patients with colorectal adenomas, 691 (33.0%) were diagnosed with flat adenomas, 514 with concomitant protruding adenomas and 177 without. The “per-patient” AMR for flat adenomas was 43.3% (299/691); the rates were 54.3% and 11.3%, respectively, for those with protruding adenomas and those without (OR = 9.320, 95%CI: 5.672-15.314, χ² = 99.084, P < 0.001). The “per-adenoma” AMR for flat adenomas was 44.3% (406/916). In multivariate analysis, older age, presence of concomitant protruding adenomas, poor bowel preparation, smaller adenoma size, location at the right colon, insufficient experience of the colonoscopist, and withdrawal time < 6 min were associated with an increased “per-adenoma” AMR for flat adenomas. The AMR for flat adenomas was moderately correlated with that for overall adenomas (r = 0.516, P < 0.0001). The AMR for flat adenomas during colonoscopy was high. CONCLUSION: Patient’s age, concomitant protruding adenomas, bowel preparation, size and location of adenomas, proficiency of the colonoscopist, and withdrawal time are factors affecting the “per-adenoma” AMR for flat adenomas.     

Video capsule enteroscopy in the diagnosis of celiac disease: a multicenter study

OBJECTIVES: Duodenal biopsy is the current gold standard for diagnosis of celiac disease. Videocapsule endoscopy examines the entire small bowel and allows visualization of mucosal villi. We evaluated the potential of videocapsule endoscopy in assessing the severity and extent of mucosal changes in patients with suspected celiac disease. METHODS: Consecutive patients with signs/symptoms suggesting celiac disease and positive anti-gliadin and/or anti-endomysial and/or anti-tissue transglutaminase antibodies underwent upper gastrointestinal endoscopy and videocapsule endoscopy. Duodenal biopsies were classified according to modified Marsh's criteria. Capsule findings were evaluated for the presence of lesions compatible with celiac disease (scalloping of duodenal folds, fissures, flat mucosa, and mosaic appearance). RESULTS: Forty-three patients were studied. Duodenal histology was normal in 11 and compatible with celiac disease in 32. Using duodenal histology as the gold standard, the performance characteristics of capsule endoscopy for the diagnosis of celiac disease were: sensitivity 87.5% (95% CI 76.1-98.9%), specificity 90.9% (95% CI 81.0-100%), positive predictive value 96.5% (95% CI 90.1-100%), negative predictive value 71.4% (95% CI 55.8-87%), positive and negative likelihood ratios 9.6 and 0.14, respectively. Eighteen patients had mucosal changes extending beyond the duodenum, involving the entire small bowel in three. These patients tended to have more severe symptoms, but the difference was not statistically significant. Interobserver agreement for the diagnosis of celiac disease by capsule endoscopy ranged between 79.2 and 94.4%; kappa values ranged between 0.56 and 0.87. CONCLUSIONS: Videocapsule endoscopy shows good sensitivity and excellent specificity for the detection of villous atrophy in patients with suspected celiac disease.     

Risk factors associated with inflammatory bowel disease: A multicenter case-control study in Brazil

BACKGROUND The etiology of inflammatory bowel disease(IBD) is unknown, but it is believed to be multifactorial. The hygiene hypothesis proposes that better hygiene conditions would lead to less infectious disease during childhood and favor the development of immune-mediated diseases.AIM To test the hygiene hypothesis in IBD by assessing the environmental risk factors associated with IBD development in different regions of Brazil with diverse socioeconomic development indices.METHODS A multicenter case-control study was carried out with 548 Crohn's disease(CD) and 492 ulcerative colitis(UC) outpatients and 416 healthy controls, from six IBD centers within different Brazilian states at diverse socioeconomic development stages. A semi-structured questionnaire with 87 socioeconomic and environmental questions was applied. Logistic regression model was created to assess the odds ratio(OR) with P value and 95% confidence intervals(CI).RESULTS Predictive variables for both diseases(CD and UC) were women [odd ratios(OR) = 1.31; OR = 1.69], low monthly family income(OR = 1.78; OR = 1.57), lower number of cohabitants(OR = 1.70; OR = 1.60), absence of vaccination(OR = 3.11; OR = 2.51), previous history of bowel infections(OR = 1.78; OR = 1.49), and family history of IBD(OR = 5.26; OR = 3.33). Associated risk factors for CD were age(18-39 years)(OR = 1.73), higher educational level(OR = 2.22), absence of infectious childhood diseases(OR = 1.99). The UC predictive variables were living in an urban area(OR = 1.62), inadequate living conditions(OR = 1.48) and former smokers(OR = 3.36). Appendectomy was a risk factor for CD(OR = 1.58) with inverse association with UC(OR = 4.79). Consumption of treated and untreated water was associated with risk of CD(OR = 1.38) and UC(OR = 1.53), respectively.CONCLUSION This is the first examining environmental exposures as risk factors for inflammatory bowel disease in Brazil. Most of the variables associated with disease risk support the role of the hygiene hypothesis in IBD development.     

Factors that impact health-related quality of life in adults with celiac disease： A multicenter study

AIM： TO evaluate the factors involved in the impairment of health-related quality of life （HRQOL） in patients with celiac disease. METHODS： A multicenter, cross-sectional prospective study was performed in patients with celiac disease who completed two HRQOL questionnaires： the gastrointestinal quality of life index （GIQLI） and the EuroQol-5D （EQ）. RESULTS： Three hundred and forty patients （163 controlled with a gluten-free diet, and 177 newly diagnosed with a normal diet） were included. The GIQLI score was significantly better in patients on a gluten- free diet （GFD） than in non-treated patients on their usual diet, both in terms of the overall score （3.3 vs 2.7, respectively; P 〈 0.001）, as well as on the individual questionnaire dimensions. Both the preference value of the EQ as the visual analogue scale were significantly better in treated than in non-treated patients （0.93 vs 0.72 P 〈 0.001 and 80 vs 70 P 〈 0.001, respectively）. Variables significantly associated with a worse HRQOL score were female gender, failure to adhere to a GFD, and symptomatic status. CONCLUSION： In untreated celiac disease, the most important factors that influence patient perception ofhealth are the presence of symptoms and a normal diet. HRQOL improves to levels similar to those described in the general population in celiac disease patients well controlled with a GFD.     

Prevalence of pruritus in patients with chronic liver disease: A multicenter study

Aim

Pruritus is a common comorbidity in chronic liver disease. The aim of this study was to clarify the prevalence of pruritus and its characteristics in patients with chronic liver disease.

Methods

A total of 1631 patients with chronic liver disease who attended one of nine joint‐research facilities from January to June 2016 were enrolled. We investigated the prevalence of pruritus, itch location, itch duration, daily itch fluctuation, seasonal itch exacerbation, treatment drugs, and therapeutic effects using a medical interview questionnaire.

Results

The median age was 66 years and 890 (54.6%) patients were women. The prevalence of pruritus was 40.3% (658/1631), and it differed according to the underlying liver disease. The most frequent body location for pruritus was on the back (63.1%). Pruritus duration was more than 6 months in 252 (38.3%) patients. The severity of pruritus, assessed using a visual analog scale, was higher during the day than at night (median, 4 vs. 3, P < 0.001). Seasonal exacerbation was observed in 296 (45.0%) patients. Although 301 (45.7%) patients were treated with antipruritic agents, 57.8% (174/301) patients reported an insufficient effect. Active hepatitis B virus infection (odds ratio [OR], 2.51; P = 0.043), primary biliary cholangitis (OR, 3.69; P = 0.018), diabetes (OR, 1.57; P = 0.010), and aspartate aminotransferase ≥60 U/L (OR, 2.06; P = 0.011) were independent factors associated with pruritus.

Conclusion

The prevalence of pruritus varies according to the chronic liver disease etiology. Underlying liver disease, aspartate aminotransferase ≥60 U/L, and comorbid diabetes are factors associated with pruritus in patients with chronic liver disease.     

Risk of proximal colorectal neoplasia among asymptomatic patients with distal hyperplastic polyps

PURPOSE: Many guidelines on colorectal cancer screening do not consider distal hyperplastic polyps to be a marker for proximal neoplasia. However, 11 of 17 published studies have shown an increased risk of proximal neoplasia in patients with distal hyperplastic polyps. Our goal is to assess the risk of proximal neoplasia in asymptomatic patients with distal hyperplastic polyps, compared to those with distal tubular adenomas or no distal polyps. METHODS: We assessed proximal (cecum, ascending, transverse colon and splenic flexure) and distal polyps in patients undergoing screening colonoscopy, classifying them into 3 groups: distal hyperplastic polyps only; distal adenomas with or without hyperplastic polyps; no distal polyps. The prevalence of proximal neoplasia and advanced neoplasia (polyps > or =1 cm, villous adenomas, or cancer) was compared among these groups. RESULTS: Of 2357 patients, 427 (18%) had neoplasia, including 103 (4%) with advanced neoplasia. Proximal neoplasia occurred in 175 (9%) of 1896 patients with no distal polyps, compared with 28 (12%) of 237 with distal hyperplastic polyps (P = 0.20) and 64 (29%) of 224 with distal adenomas (P <0.0001). Proximal advanced neoplasia occurred in 39 (2%) patients with no distal polyps, compared with 4 (2%) with distal hyperplastic polyps (P = 0.70) and 9 (4%) with distal adenomas (P = 0.13). CONCLUSIONS: Patients with distal hyperplastic polyps, unlike those with distal adenomas, do not exhibit an increased risk for proximal neoplasia or proximal advanced neoplasia compared to those with no distal polyps. The discovery of hyperplastic polyps on screening sigmoidoscopy should not prompt colonoscopy.     

Risk of colorectal cancer in patients with hematologic disease

BACKGROUND AND AIMS: A relatively large number of patients with multiple myeloma have been reported to develop a secondary malignancy such as cancer of the breast, biliary system or bowel. METHODS: A retrospective study was perfomed in 734 patients with hematologic disease diagnosed at Nippon Medical School Hospital between May 1984 and September 1994 to determine the incidence of colorectal cancer in these patients based on a history review, colonoscopic findings, and surgical or autopsy data. RESULTS: Of the 734 patients, 14 (1.9%) had colorectal cancer; two of 11 patients (18.2%) had pure red cell aplasia; two of 25 patients (8%) had multiple myeloma; and three of 46 patients (6.5%) had aplastic anemia. Patients with pure red cell aplasia, multiple myeloma or aplastic anemia had colorectal cancer at a significantly higher rate compared to those with leukemia (P< 0.005, P< 0.02, P< 0.01, respectively). CONCLUSIONS: It is possible that a relatively large number of patients with pure red cell aplasia, multiple myeloma or aplastic anemia will develop a colorectal cancer.     

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.