Positive Celiac Disease Serology Research Articles

Risk of Lymphoproliferative Malignancy in Relation to Small Intestinal Histopathology Among Patients With Celiac Disease

Celiac disease is associated with an increased risk of malignant lymphomas. The risk of lymphoproliferative malignancies in patients with small intestinal inflammation without villous atrophy and in patients with latent celiac disease is unknown. We performed a cohort study using duodenal and jejunal biopsy data that were collected from all 28 Swedish pathology departments (July 1969 to February 2008). We identified two population-based cohorts composed of 28,989 individuals with biopsy-verified celiac disease (villous atrophy, Marsh stage 3) and 13,140 individuals with small intestinal inflammation without villous atrophy (Marsh 1 + 2) and a regional cohort of 3711 individuals with latent celiac disease (positive celiac disease serology and normal mucosa). Cancer data were obtained by linkage to the National Cancer Registry. We used Cox regression to estimate hazard ratios (HRs) for lymphoproliferative malignancy and any solid cancer among the three cohorts compared with a total of 227,911 age- and sex-matched reference individuals. Although biopsy-verified celiac disease and intestinal inflammation were associated with lymphoproliferative malignancy (for celiac disease, HR = 2.82; 95% confidence interval [CI] = 2.36 to 3.37, n = 193; for inflammation, HR = 1.81; 95% CI = 1.42 to 2.31, n = 89), latent celiac disease was not associated with lymphoproliferative malignancy (HR = 0.97; 95% CI = 0.44 to 2.14, n = 7). The absolute rates of lymphoproliferative malignancies among persons with celiac disease, small intestinal inflammation, and latent celiac disease were 70.3 per 100,000 person-years, 83.4 per 100,000 person-years, and 28.0 per 100,000 person-years, respectively. Compared with individuals with celiac disease, individuals with small intestinal inflammation or latent celiac disease were at a statistically significantly lower risk of lymphoproliferative malignancy. Risk of any solid cancer was not increased beyond the first year of follow-up in any cohort. Celiac disease was associated with Hodgkin lymphoma and both T-cell and B-cell non-Hodgkin lymphomas. The risk of lymphoproliferative malignancy in celiac disease is dependent on small intestinal histopathology, with no increased risk in latent celiac disease.

Nationwide Cohort Study of Risk of Ischemic Heart Disease in Patients With Celiac Disease

Studies on ischemic heart disease (IHD) incidence in individuals with celiac disease (CD) are contradictory and do not take small intestinal pathology into account. In this Swedish population-based cohort study, we examined the risk of IHD in patients with CD based on small intestinal histopathology. We defined IHD as death or incident disease in myocardial infarction or angina pectoris in Swedish national registers. In 2006 to 2008, we collected duodenal/jejunal biopsy data on CD (equal to villous atrophy; Marsh 3; n=28 190 unique individuals) and inflammation without villous atrophy (Marsh 1 to 2; n=12 598) from all 28 pathology departments in Sweden. A third cohort consisted of 3658 individuals with normal mucosa but positive CD serology (Marsh 0, latent CD). We found an increased risk of incident IHD in patients undergoing small intestinal biopsy that was independent of small intestinal histopathology (CD: hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.11 to 1.28; 991 events; inflammation: HR, 1.28; 95% CI, 1.19 to 1.39; 809 events; and latent CD: HR, 1.14; 95% CI, 0.87 to 1.50; 62 events). Celiac disease (HR, 1.22; 95% CI, 1.06 to 1.40) and inflammation (HR, 1.32; 95% CI, 1.14 to 1.52) were both associated with death resulting from IHD, whereas latent CD was not (HR, 0.71; 95% CI, 0.34 to 1.50). Individuals with CD or small intestinal inflammation are at increased risk of incident IHD. We were unable to show a positive association between latent CD and incident IHD.

Increased Risk of Hospital Admission for Influenza in Patients With Celiac Disease: A Nationwide Cohort Study in Sweden

Although earlier studies suggest an increased risk of infectious disease in celiac disease (CD), data on the risk of influenza in patients with CD are limited. We examined the risk of hospital admission for influenza in CD patients, but for comparative reasons also in individuals with small-intestinal inflammation or normal mucosa but positive CD serology. In 2006-2008, we collected duodenal/jejunal biopsy data on CD (Marsh 3: villous atrophy, VA; n=29,008 unique individuals) and inflammation (Marsh 1-2; n=13,200) from all 28 pathology departments in Sweden. A third regional cohort consisted of 3,709 individuals with positive CD serology but normal mucosa (Marsh 0). The biopsies were performed between 1969 and 2008. Through linkage with the Swedish Hospital Discharge Register, we estimated the risk of hospital admission for influenza compared with that of 224,114 age- and sex-matched controls from the general population. Individuals with CD were at increased risk of hospital admission for influenza (hazard ratio (HR)=2.1; 95% confidence interval (CI)=1.6-2.7; n=81). The absolute risk of influenza was 30/100,000 person-years (excess risk: 16/100,000 person-years). Furthermore, children with CD were at increased risk of influenza (HR=2.5; 95% CI=1.3-4.8). Whereas individuals with inflammation without VA were also at increased risk of influenza (HR=1.9; 95% CI=1.4-2.5), individuals with normal mucosa but positive CD serology were not (HR=1.2; 95% CI=0.5-3.0). This study found an increased risk of hospital admission for influenza in patients with CD.

Positive Celiac Disease Serology and Reduced Bone Mineral Density in Adult Women

Low bone density and osteoporosis have been demonstrated in celiac disease populations in Europe, South America and the United States. Serological testing with tissue transglutaminase (TTG) and immunoglobulin A endomysial (EMA) antibodies is highly specific for celiac disease, while antigliadin antibody (AGA) testing is less specific. To evaluate the association of celiac serology with reduced bone density in adult women. A clinical database containing all bone density testing data in the province of Manitoba was linked to a database containing all celiac serology data for the province. The study cohort consisted of 376 women older than 20 years of age with bone density measurements preceding initial celiac serology by six months or less. Bone density was assessed in relation to TTG/EMA and AGA seropositivity, and compared with seronegative controls in age-, height- and weight-adjusted models. There was significantly lower bone density in TTG/EMA seropositive women than with seronegative controls for all sites tested (lumbar spine, total hip, trochanter, femoral neck; all P<0.05). TTG/ EMA seropositive women also had a significantly higher prevalence of osteoporosis (67.7% versus 44.8%; P<0.05). There was lower bone density at the three hip sites (all P<0.05) in AGA seropositive women, but after excluding TTG/EMA seropositive women, isolated AGA seropositivity showed no significant association with any bone density measurements. TTG/EMA seropositivity was associated with lower bone density and a higher prevalence of osteoporosis compared with seronegative controls.

Increased Risk of Death for Patients With Celiac Disease-Related Disorders

New research indicates that patients with lesser degrees of celiac disease-related symptoms, such as intestinal inflammation or latent celiac disease, have a modestly increased risk of death, according to a study in the September 16, 2009 issue of JAMA. Although most research has shown an increased risk of death in celiac disease, less is known about the long-term consequences of nonspecific small intestinal inflammation without villous atrophy. Research on other inflammatory disorders suggests that inflammation may be associated with increased mortality, but this has not been investigated for nonspecific inflammation in the small intestine. Jonas F. Ludvigsson, MD, PhD, of Örebro University Hospital, örebro, Sweden, and colleagues used nationwide histopathology data collected from biopsies taken between July 1969 and February 2008 in Sweden to examine overall mortality risk in individuals with celiac disease and inflammation. Data from the biopsies was divided into three groups: celiac disease (Marsh stage 3, villous atrophy; n = 29,096 individuals); inflammation (Marsh stage 1–2; n = 13,306); and individuals with latent celiac disease (n = 3719). Latent celiac disease was defined as positive celiac disease serology in individuals with normal intestinal mucosa. Through linkage with the Swedish Total Population Register, the researchers estimated the risk of death through August 2008, compared with age- and gender-matched controls from the general population. The data indicated there were 3049 deaths among patients with celiac disease, 2967 deaths in patients with inflammation, and 183 deaths with latent celiac disease. The study found mortality risk was increased in all 3 groups, with patients with inflammation having a 72% increased risk; patients with celiac disease, a 39% increased risk; and patients with latent celiac disease having a 35% increased mortality risk. The risk of death was highest in the first year of follow-up, with celiac disease associated with a 2.8-fold increased risk of death, inflammation with a 4.7-fold increase, and latent celiac disease with a 1.8-fold increase. After the first year of follow-up, these figures decreased. Mortality risk also decreased with age at diagnosis, with risk being higher for those diagnosed before age 20. “In conclusion, we found increased [risks] for death in individuals with biopsy-verified celiac disease, inflammation, and latent celiac disease, although absolute risks were small” the authors note. “Individuals undergoing small-intestinal biopsy in childhood had increased [risks] for death. Cardiovascular disease and malignancy were the main causes of death in celiac disease.” Peter H. R. Green, MD, of Columbia University College of Physicians and Surgeons, New York, writes in an accompanying editorial that this study provides important information on the risks associated with celiac disease. “Until recently, gluten sensitivity has received little attention in the traditional medical literature, although there is increasing evidence for its presence in patients with various neurological disorders and psychiatric problems. The study by Ludvigsson and colleagues reinforces the importance of celiac disease as a diagnosis that should be sought by physicians. It also suggests that more attention should be given to the lesser degrees of intestinal inflammation and gluten sensitivity.” See: JAMA 2009;302:1171–1178 and 1225–1226.

Small-Intestinal Histopathology and Mortality Risk in Celiac Disease

Studies of mortality in celiac disease have not taken small-intestinal pathology into account. To examine mortality in celiac disease according to small-intestinal histopathology. Retrospective cohort study. We collected data from duodenal/jejunal biopsies taken between July 1969 and February 2008 on celiac disease (Marsh stage 3: villous atrophy; n = 29,096 individuals) and inflammation (Marsh stage 1-2; n = 13,306) from all 28 pathology departments in Sweden. A third cohort consisted of individuals with latent celiac disease from 8 university hospitals (n = 3719). Latent celiac disease was defined as positive celiac disease serology in individuals with normal mucosa (Marsh stage 0). Through linkage with the Swedish Total Population Register, we estimated the risk of death through August 31, 2008, compared with age- and sex-matched controls from the general population. All-cause mortality. There were 3049 deaths among patients with celiac disease, 2967 with inflammation, and 183 with latent celiac disease. We found an increased hazard ratio (HR) for death in celiac disease (HR, 1.39; 95% confidence interval [CI], 1.33-1.45; median follow-up, 8.8 years), inflammation (HR, 1.72; 95% CI, 1.64-1.79; median follow-up, 7.2 years), and latent celiac disease (HR, 1.35; 95% CI, 1.14-1.58; median follow-up, 6.7 years). The absolute mortality rate was 10.4 (95% CI, 10.0-10.8) per 1000 person-years in celiac disease, 25.9 (95% CI, 25.0-26.8) in inflammation, and 6.7 (95% CI, 5.7-7.6) in latent celiac disease. Excess mortality was 2.9 per 1000 person-years in celiac disease, 10.8 in inflammation, and 1.7 in latent celiac disease. This risk increase was also seen in children. Excluding the first year of follow-up, HRs decreased somewhat. Risk of death among patients with celiac disease, inflammation, or latent celiac disease is modestly increased.

Celiac disease and Budd Chiari syndrome: report of a case with review of literature

We here report a case of celiac disease and Budd Chiari syndrome. This 19-year-old boy was diagnosed to have portal hypertension in another hospital when he had developed variceal bleeding. In our hospital, he was found to have occlusion of all three hepatic veins as the cause of portal hypertension. On a routine endoscopy, he was found to have scalloping of duodenal folds. Suspecting celiac disease, he was investigated further. He did have positive serology for celiac disease as well as suggestive histology. He was found to be deficient for protein C and protein S. He was managed conservatively and put on gluten-free diet, with which he showed clinical improvement. A review of literature showed that only 14 previous cases of this combination were recorded and except for one all were from North Africa or southern Europe.

Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa

BackgroundAntibody serology is an important tool in the investigation of celiac disease (CD), but does not always correlate with mucosal appearance in the small intestine. Patients with positive CD serology but normal mucosa (Marsh 0) are at increased risk of future CD. In this study we describe a model for identifying and characterizing individuals with normal mucosa but positive CD serology. Such individuals are sometimes referred to as having latent CD.MethodsThe records of ten Swedish pathology departments were used to identify individuals with biopsies indicating normal duodenal/jejunal mucosa. Using the national personal identification number, these data were linked with CD serology data (antigliadin, antiendomysial and tissue transglutaminase antibodies); and we thereby identified 3,736 individuals with normal mucosa but positive CD serology. Two independent reviewers then manually reviewed their biopsy reports to estimate comorbidity. We also randomly selected 112 individuals for validation through patient chart review.ResultsThe majority of the 3,736 individuals were females (62%). Children (0–15 years) made up 21.4%. The median number of biopsy specimen was 3. Our review of biopsy reports found that other gastrointestinal comorbidity was rare (inflammatory bowel disease: 0.4%; helicobacter pylori infection: 0.2%). Some 22% individuals selected for patient chart review had a relative with CD. The most common symptoms among these individuals were diarrhea (46%) and abdominal pain (45%), while 26% had anemia. Although 27% of the individuals selected for validation had been informed about gluten-free diet, only 13% were adhering to a gluten-free diet at the end of follow-up.ConclusionIndividuals with positive CD serology but normal mucosa often have CD-like symptoms and a family history of CD.

Validation study of villous atrophy and small intestinal inflammation in Swedish biopsy registers

BackgroundSmall intestinal biopsy with villous atrophy (VA) is the gold standard for the diagnosis of celiac disease (CD). We validated VA (Marsh 3) and small intestinal inflammation without VA (Marsh 1+2) in Swedish regional biopsy registers.MethodsAll pathology departments in Sweden (n = 28) were searched to identify individuals with VA or duodenal/jejunal inflammation. The validation consisted of blinded examination of biopsy samples, manual review of biopsy reports, web surveys, and patient chart reviews of 121 individuals with VA and 39 with inflammation.ResultsWe identified 29,148 individuals with VA and 13,446 individuals with inflammation. In a blinded examination, Swedish pathologists correctly classified 90% of biopsies with VA. Manual screening of 1,534 biopsy reports (performed by co-author JFL and a research assistant) found that comorbidity other than CD was rare. IBD was the most common comorbidity and occurred in 0.3% of biopsies with VA (1.6% in inflammation). Among 114 patients with VA and available data, 108 (95%) had a clinical diagnosis of CD. 79% of the validated individuals with VA and 64% of those with inflammation had documented gastrointestinal symptoms prior to biopsy. 88% of the validated individuals with VA had positive CD serology before their first biopsy. 172/180 (96%) of Swedish gastroenterologists and 68/68 (100%) of pediatricians perform a small intestinal biopsy in at least 9 out of 10 individuals prior to diagnosis of CD.ConclusionRegional biopsy data are feasible to identify individuals with CD and small-intestinal inflammation. The specificity of CD is high in villous atrophy.

Maladie cœliaque et accidents vasculaires cérébraux ischémiques

Introduction Neurological manifestations of celiac disease are various. An association with ischemic stroke is not common and has not been well documented. We report two cases. Observations The first patient had experienced several transient ischemic strokes in the past 2 years and then had an acute ischemic stroke involving the territory of the right posterior cerebral artery. Investigations revealed celiac disease with no other recognizable etiology. The clinical course was marked by persistent visual aftereffects, but no new vascular event. The second patient had been followed since 1998 for celiac disease confirmed by pathology and serology tests. She was on a gluten-free diet. The patient had an ischemic stroke involving the territory of the left middle cerebral artery. Apart from a positive serology for celiac disease and iron deficiency anemia, the etiological work-up was negative. Discussion The mechanisms of vascular involvement in celiac disease are controversial. The most widely incriminated factor is autoimmune central nervous system vasculitis, in which tissue transglutaminase, the main auto-antigen contributing to maintaining the integrity of endothelium tissue, plays a major role. Other mechanisms are still debated, mainly vitamin deficiency. Conclusion Being a potentially treatable cause of ischemic stroke, celiac disease must be considered as a potential etiology of stroke of unknown cause, particularly in young patients, and even without gastrointestinal manifestations.

Screening for celiac disease in idiopathic pulmonary hemosiderosis

The aim of this report was to screen for celiac disease (CD) in patients with idiopathic pulmonary hemosiderosis (IPH). Patients with IPH treated at the Children's Hospital of Tunis between 1976 and 2006 were reviewed and investigated for CD, using serological and histological tests. A total of 10 children (two boys and eight girls) had IPH. The mean age at diagnosis was 3.1 years. Three had digestive symptoms and positive CD serology, which was confirmed by histological data. Clinical and radiological findings improved markedly in all CD patients with corticosteroid treatment combined with a gluten-free diet. Symptoms of IPH and CD both returned in one patient who stopped the gluten-free diet. Three of our 10 patients with IPH also had CD. These data illustrate the close etiopathogenic link between IPH and CD, and strongly suggest that CD be looked for in IPH patients, especially in those with symptoms suggestive of CD.

Celiac Disease Refractory to a Gluten-free Diet?

A 75-year-old woman from an outside hospital was referred because of continued signs and symptoms of celiac disease (gluten-sensitive enteropathy) that persisted despite self-reported adherence to a gluten-free diet. The patient reported excessive gas, bowel distension, a 15-pound weight loss over the past few years, insomnia, and a rash over her lower extremities. The patient had required hospitalizations, intravenous fluids, and continuing therapy with corticosteroids for 6 months. A diagnosis of celiac disease had been made 6 years previously, based on (a) typical gastrointestinal signs and symptoms with negative stool cultures and Clostridium difficile toxin assay, (b) positive serology for celiac disease, (c) unremarkable colonoscopy with normal random biopsy results, and (d) small-bowel biopsy results showing evidence of villous blunting with increased chronic inflammatory cells. At that time, the patient’s laboratory results included antigliadin antibody (AGA) IgG 0.8 AU (<10 AU), anti-AGA IgA 1.1 AU (<5 AU), anti–tissue transglutaminase (tTG) IgA 9.2 AU (<4 AU), and normal total IgA and IgA antiendomysial antibody (EMA) values. A computed tomographic scan was negative for lymphoma, and an upper gastrointestinal series and small-bowel follow-through barium x-ray were normal. Endoscopic biopsy results obtained during the previous 2 years showed continued villous atrophy with intraepithelial lymphocytes. Shortly before the patient’s referral, repeat biopsies showed villous blunting with increased chronic inflammation, findings confirmed by a gastrointestinal pathologist at our institution. The patient, a pleasant, frail-looking, elderly woman in no acute distress, was retired and married with 2 adult children. She denied smoking and alcohol use and had no family history of celiac disease, liver disease, or colon cancer. Her medical history was remarkable for placement of a carotid artery stent 5 years earlier. Physical examination was unremarkable except for the presence of a maculopapular rash inconsistent with dermatitis herpetiformis and with dependent distribution over the lower …

Celiac disease in intrauterine growth restriction

Celiac disease (CD) has been defined as a state of permanent intolerance to gluten which can be treated by a gluten-free diet and food supplements. Atypical celiac disease with only extraintestinal symptoms may be more frequent than the classical celiac disease. It has been shown that women with celiac disease experience a wide range of reproductive disorders including recurrent spontaneous miscarriage delayed menarche early menopause amenorrhoea and vaginal discharge and also intrauterine growth restriction (IUGR). The present study first of its kind in India aims to assess the frequency of latent celiac disease by means of serology in pregnant females with IUGR. The sample size of the present case controlled study was based on the reported incidence of positive serology for celiac disease in women having IUGR of around 15%. With power of test being 80% and at a chance level of 5% the estimated sample size was 45 females in each group. IgA antitissue transglutaminase antibodies are now recommended as the first-line serological test for celiac disease. The institutional ethical committee approved this study. (authors)

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

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. 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. 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. 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.

Celiac disease: India on the global map

Celiac disease: India on the global map

Celiac Disease in Children With Migraine

To the Editor. In an interesting article, Zelnik et al1 recently investigated the presence of neurologic disorders in patients with celiac disease (CD). They found those disorders to be more common in children with CD (51.4%) than in controls (19.9%). The authors also demonstrated therapeutic benefit with gluten-free diet only in patients with hypotonia or migraine. On the other hand, Gabrielli et al2 reported positive serology for CD in a significantly higher percentage of patients with migraine than in a control …

HLA-DQ typing in the diagnosis of celiac disease

OBJECTIVE: More than 95% of celiac patients share the major histocompatibility complex II class human leukocyte antigen (HLA) DQ2 or DQ8 haplotype; patients negative for both types are unlikely to suffer from celiac disease. Our aim was to investigate whether HLA-DQ2 and -DQ8 typing is helpful when diagnosis is uncertain because of the absence of unequivocal small bowel villous atrophy. METHODS: HLA-DQ2 and -DQ8 typing was carried out in 59 patients evincing nondiagnostic small bowel mucosal lesion or positive celiac serology, and in 17 patients maintaining a gluten-free diet without biopsy-proven celiac disease. HLA findings were compared to small bowel mucosal morphology; intraepithelial lymphocytes; and serum endomysial (EmA), reticulin, tissue transglutaminase (anti-tTG) and gliadin antibodies. RESULTS: Of the 59 patients evincing only minor small bowel mucosal changes or positive celiac disease serology, 22 (37%) were negative for DQ2 and DQ8. All EmA-positive patients had celiac-type HLA, but antireticulin antibody, anti-tTg, and antigliadin antibody were also present in HLA-DQ2– and -DQ8–negative individuals. Eleven of 17 patients (65%) observing a gluten-free diet before small bowel biopsy did not share celiac-type HLA. None of the 17 had apparent villous atrophy. Serum EmA and anti-tTG were negative in all. HLA-DQ typing is less expensive than follow-up biopsy in the exclusion of celiac disease. CONCLUSIONS: HLA-DQ2 and -DQ8 determination is useful in exclusion, probably lifelong, of celiac disease in individuals with an equivocal small bowel histological finding. The low specificity of this test must, however, be borne in mind.