Celiac Abstracts 6

© 2011

Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet

            (Bene, Komlosi et al. 2005) Download

AIM: To determine the fasting plasma carnitine ester in patients with celiac disease. METHODS: We determined the fasting plasma carnitine ester profile using ESI triple quadrupol mass spectrometry in 33 adult patients with biopsy-confirmed maturity onset celiac disease maintained on long term gluten free diet. RESULTS: The level of free carnitine did not differ as the celiac disease patients were compared with the healthy controls, whereas the acetylcarnitine level was markedly reduced (4.703 +/- 0.205 vs 10.227 +/-0.368 nmol/mL, P<0.01). The level of propionylcarnitine was 61.5%, butyrylcarnitine 56.9%, hexanoylcarnitine 75%, octanoylcarnitine 71.1%, octenoylcarnitine 52.1%, decanoylcarnitine 73.1%, cecenoylcarnitine 58.3%, lauroylcarnitine 61.5%, miristoylcarnitine 66.7%, miristoleylcarnitine 62.5% and oleylcarnitine 81.1% in the celiac disease patients compared to the control values, respectively (P<0.01). CONCLUSION: The marked decrease of circulating acetylcarnitine with 50-80 % decrease of 11 other carnitine esters shows that the carnitine ester metabolism can be influenced even in clinically asymptomatic and well being adult celiac disease patients, and gluten withdrawal alone does not necessarily normalize all elements of the disturbed carnitine homeostasis.

        

Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial

            (Biesiekierski, Newnham et al. 2011) Download

OBJECTIVES: Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism. METHODS: A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. RESULTS: A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8. CONCLUSIONS: "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated.

L-Carnitine in the treatment of fatigue in adult celiac disease patients: a pilot study

            (Ciacci, Peluso et al. 2007) Download

BACKGROUND: Fatigue is common in celiac disease. L-Carnitine blood levels are low in untreated celiac disease. L-Carnitine therapy was shown to improve muscular fatigue in several diseases. AIM: To evaluate the effect of L-carnitine treatment in fatigue in adult celiac patients. METHODS: Randomised double-blind versus placebo parallel study. Thirty celiac disease patients received 2 g daily, 180 days (L-carnitine group) and 30 were assigned to the placebo group (P group). The patients underwent clinical investigation and questionnaires (Scott-Huskisson Visual Analogue Scale for Asthenia, Verbal Scale for Asthenia, Zung Depression Scale, SF-36 Health Status Survey, EuroQoL). OCTN2 levels, the specific carnitine transporter, were detected in intestinal tissue. RESULTS: Fatigue measured by Scott-Huskisson Visual Analogue Scale for Asthenia was significantly reduced in the L-carnitine group compared with the placebo group (p=0.0021). OCTN2 was decreased in celiac patients when compared to normal subjects (-134.67% in jejunum), and increased after diet in both celiac disease treatments. The other scales used did not show any significant difference between the two celiac disease treatment groups. CONCLUSION: L-Carnitine therapy is safe and effective in ameliorating fatigue in celiac disease. Since L-carnitine is involved in muscle energy production its decreased absorption due to OCTN2 reduction might explain muscular symptoms in celiac disease patients. The diet-induced OCTN2 increase, improving carnitine absorption, might explain the L-carnitine treatment efficacy.


HLA-DQ Genotyping Combined With Serological Markers for the Diagnosis of Celiac Disease: Is Intestinal Biopsy Still Mandatory?

            (Clouzeau-Girard, Rebouissoux et al. 2011) Download

OBJECTIVES:: The aim of this study was to evaluate the value of HLA-DQ2/DQ8 allelic genotyping combined with serologic testing for the diagnosis of celiac disease (CD). PATIENTS AND METHODS:: One hundred seventy children, who underwent jejunal biopsy for digestive symptoms or malnutrition, were tested for HLA-DQ2/DQ8 and serologic markers (tTG and/or anti-endomysial antibodies). Children were classified in 2 groups, according to jejunal histology: group 1, when partial or total villous atrophy was associated with an increased intraepithelial lymphocytosis suggesting CD, and group 2, when these histological criteria were absent. RESULTS:: Eight children were excluded from the study because their intestinal histology was not informative; 82 children were classified in group 1 and 80 in group 2. Eighty-one of 82 children in group 1 were positive for HLA and serologic testing. The other child had negative HLA and serologic testing but marked villous atrophy, and further investigation showed an allergic disease. Among the 80 children in group 2, 53 were negative for both HLA and serologic testing, 22 were positive for HLA but negative for serologic testing, 2 were negative for HLA and positive for serologic testing, and 3 patients were positive for both HLA and serologic testing. The last 3 children were shown to have an autoimmune background and had probably a latent form of CD. The association of HLA-DQ2/DQ8 and serologic markers had a sensitivity of 98.8%, a specificity of 96.2%, a positive likelihood ratio of 26.3, and a negative likelihood ratio of 0.013. CONCLUSIONS:: The association of positive HLA-DQ2/DQ8 and serologic testing has a high predictive value for CD. We suggest that symptomatic children with high titers of immunoglobulin (Ig)A tTG could be diagnosed as patients with CD without performing jejunal biopsy. In other children, HLA-DQ2/DQ8 could be useful to exclude the diagnosis of CD if negative. In cases of low IgA tTG titers or in patients with IgA deficiency, intestinal biopsy remains mandatory.

Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children

            (Decker, Engelmann et al. 2011) Download

OBJECTIVES: The aim of this study was to analyze a possible association between cesarean delivery and enteric inflammatory diseases in children. METHODS: A retrospective, multicenter, case-control study that included 1950 children was performed in cooperation with 26 university and 16 nonacademic children's hospitals. Information on intestinal disease manifestation, together with mode of delivery and gestational age at birth, postnatal complications, and breastfeeding, was collected by the attending physician from children and their parents who were visiting a gastrointestinal outpatient clinic for Crohn disease (CD; 516 cases), ulcerative colitis (250 cases), celiac disease (157 cases), and other gastrointestinal diseases (165 cases) and control subjects who were visiting ophthalmologic, orthodontic, and dental outpatient clinics (862 cases). RESULTS: Whereas the rate of cesarean delivery of children with Crohn disease or ulcerative colitis was similar to that of control subjects, a significantly enhanced likelihood of being born by cesarean delivery was found in children with celiac disease compared with control subjects (odds ratio: 1.8 [95% confidence interval: 1.13-2.88]; P = .014). CONCLUSIONS: The mode of delivery and associated alterations in the development of the enteric homeostasis during the neonatal period might influence the incidence of celiac disease.

Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens

            (DePaolo, Abadie et al. 2011) Download

Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens. A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat. The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses. Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients, retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphorylation and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens.

Stroke and dilated cardiomyopathy associated with celiac disease

            (Dogan, Peker et al. 2010) Download

Celiac disease (CD) is manifested by a variety of clinical signs and symptoms that may begin either in childhood or adult life. Neurological symptoms without signs of malabsorption have been observed for a long time in CD. In this report, an 8-year-old girl with CD presented with rarely seen dilated cardiomyopathy and stroke. The girl was admitted with left side weakness. Her medical history indicated abdominal distention, chronic diarrhea, failure to thrive, and geophagia. On physical examination, short stature, pale skin and a grade 2 of 6 systolic murmur were detected. Muscle strength was 0/5 on the left side, and 5/5 on the right side. Coagulation examinations were normal. Tests for collagen tissue diseases were negative. Factor V Leiden and prothrombin GA20210 mutations were negative. Tandem mass spectrophotometry and blood carnitine profiles were normal. Brain magnetic resonance imaging and cerebral angiography showed an infarction area at the basal ganglia level. Examinations of serologic markers and intestinal biopsy revealed CD. We emphasize that in differential diagnosis of ischemic stroke, CD should be kept in mind.

Reproductive changes associated with celiac disease

            (Freeman 2010) Download

Celiac disease is a mucosal disorder of the small intestine that may be triggered by dietary exposure to gluten in genetically-susceptible individuals. The disorder is often associated with diarrhea, malabsorption and weight loss along with other extra-intestinal complications. Reproductive changes have been described, including impaired fertility and adverse pregnancy outcomes possibly related to immune-mediated mechanisms or nutrient deficiency. Other possible pathogenetic factors that may alter placental function include maternal celiac disease autoantibodies binding to placental transglutaminase, and genetic mutations that may facilitate microthrombus formation. Reports noting activation during pregnancy or the puerperium may be important, and suggest that celiac disease may also be hypothetically precipitated by maternal exposure to one or more fetal antigens.

Undiagnosed coeliac disease does not appear to be associated with unfavourable outcome of pregnancy

            (Greco, Veneziano et al. 2004) Download

BACKGROUND: In a previous hospital based study, we suggested that undiagnosed coeliac disease has a prevalence, among pregnant women, of 1:80, and is a cause of unfavourable outcome of pregnancy. AIMS: In order to confirm or dismiss this hypothesis, which has significant public health implications, we carried out a large population based study on a stratified sample from the whole Campania region. PATIENTS: During the period of the study, 5345 women were admitted to the OBS-GYN wards regional network: 5055 (95%) were enrolled in the study. METHODS: Antihuman IgA class antitissue transglutaminase (TGASE) antibodies were tested by an ELISA method. Endomysial antibodies (EMA) were investigated on thin sections of human cord blood by an immunofluorescence test. The HLA class II DQA1*0501/DQB1*02 and DQA1*0301/DQB1*0302 haplotypes were assessed using the Eurospital Eu-DQ kit. Duodenal biopsy was not considered feasible by the ethics committee for pregnant women near delivery. RESULTS: Fifty one of 5055 patients had confirmed positive results. We added to these 12 women with known coeliac disease, giving a prevalence rate for coeliac disease of 1:80 (exactly the value observed during the first study). Comparing the 51 TGASE positive with 4997 negative women, we did not observe an excess risk of abortion, premature delivery, small birth weight, or intrauterine growth retardation. Anaemia was more frequent in cases than controls. CONCLUSIONS: Undiagnosed coeliac disease is frequent among pregnant women (>1%) but is not associated with an unfavourable outcome of pregnancy.

Prevalence of celiac disease in a cohort of women with unexplained infertility

         (Jackson, Rosen et al. 2008) Download

Several European studies have suggested a higher prevalence of celiac disease (CD) among infertile women (4% to 8%) compared with the general population (<1%). We screened a cohort of women with unexplained infertility in Northern California for the serum markers of CD, tissue transglutaminase and endomysium antibodies (EMA). Given that only one woman out of 121 (0.8%) screened positive for CD, it appears that CD is about as prevalent in this cohort of infertile women as in the general U.S. population (<1%).

Anthropometric, serologic, and laboratory correlation with villous blunting in pediatric celiac disease: diabetics are different

            (Jatla, Bokhari et al. 2009) Download

OBJECTIVES: We evaluated the correlation between level of tissue transglutaminase (TTG) and endomysial antibodies (EMAs) to different degrees of intestinal damage in celiac disease (CD) children with [presence of diabetes mellitus (DM)+] and without [absence of diabetes mellitus (DM-)] type I diabetes. We also assessed the correlation between albumin, hemoglobin (hgb), transaminases, symptom presence, age of cereal introduction, and body mass index (BMI) to different degrees of intestinal damage. METHODS: Retrospective review of patients seen at the Children's Hospital of Philadelphia between January 2002 and June 2006 revealed 60 children (mean age 9.8 y) who had TTG, EMA, and other laboratory tests performed at time of histologic CD diagnosis from duodenal biopsies. Twenty-one of 60 children had DM. All children were stratified for histologic damage according to Marsh classification. RESULTS: Overall, Marsh (M) I lesions were seen in 2 (3.3%), MII in 2 (3.3%), IIIa in 14 (23.3%), IIIb in 15 (25%), and IIIc in 27 (45%); no differences in DM- versus DM+ groups. TTG was positive in all and EMA was positive in all but 1 child. Among DM- and DM+ children, median TTG and EMA values were higher with MIIIa-c, respectively. For DM-, BMI percentile, hgb, and mean corpuscular volume were lower with advancing histology. However, in DM+, no significant correlation of BMI percentile, hgb, or mean corpuscular volume with grade was observed. Cereal introduction age, hypoalbuminemia, and hepatitis did not differ between MIIIa-c in any group. CONCLUSIONS: TTG and EMA mean serum values are higher in CD children with severe enteropathy (MIIIc) than in those with mild enteropathy (MIIIa). CD in DM is accompanied by serologic and histologic findings identical to that of a non-DM CD population. As CD is identified through screening in DM, it is often silent and not associated with symptoms, growth abnormalities, or anemia. Clinical parameters (height, weight, hgb, symptoms) are not helpful in identifying silent CD in DM.

Latent celiac disease in reproductive performance of women

            (Kumar, Meena et al. 2011) Download

OBJECTIVE: To investigate the prevalence of positive serologic findings for celiac disease in Indian women with poor reproductive performance. DESIGN: Cross-sectional except that the women with intrauterine growth restriction were followed prospectively until delivery. SETTING: Department of Obstetrics and Gynecology of a tertiary teaching hospital, New Delhi. PATIENT(S): Eight hundred ninety-three women (104 women with idiopathic recurrent abortion, 104 women with unexplained stillbirth, 230 cases of unexplained infertility, 150 pregnant women with idiopathic intrauterine growth restriction, 305 control cases). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The presence of antigliadin IgA and IgG, anti-tissue transglutaminase IgA by ELISA, and IgA antiendomysium antibody by indirect immunofluorescence microscopy. RESULT(S): The seroprevalence of transglutaminase IgA was 6.70% in the group with recurrent abortion, 5.70% in the group with stillbirth, 5.65% in the group with infertility, 9.33% in the group with intrauterine growth restriction, and 1.30% in the control group. Rates of previous preterm births, low-birth-weight infants, and cesarean section were higher in seropositive women compared with seronegative subjects. CONCLUSION(S): Women having poor reproductive performance had subclinical celiac disease. The serology for celiac disease can be considered in idiopathic cases.

Balanced polymorphism: A survival advantage in celiac disease

            (Lerner 2011) Download

Coeliac disease in the father affects the newborn

         (Ludvigsson and Ludvigsson 2001) Download

BACKGROUND AND AIMS: Untreated coeliac disease in the mother is associated with lower birth weight. We examined the risk of adverse neonatal outcome when the infant's mother, father, or other relative suffered from known coeliac disease. METHODS: Mothers answered a questionnaire a few days after the birth of their infant. Of a total of 10,597 single birth infants from Southeast Sweden, 53 infants had a mother with coeliac disease (father 27, sibling 70, other close relative 442). Adjusted odds ratios and adjusted differences for neonatal outcome were calculated. RESULTS: Infants whose father suffered from coeliac disease had a lower birth weight (95% adjusted confidence interval (CI) -459, -72 g), more often belonged to the low birth weight (LBW) category (LBW < or =2499 g) (95% CI adjusted odds ratio (AOR) 1.48--17.18), and had a shorter pregnancy duration (95% adjusted CI -1.53, -0.08 weeks) than non-coeliac controls. They also weighed less than infants whose father suffered from other autoimmune diseases (95% CI -549, -93 g). Infants whose mother suffered from coeliac disease had a lower birth weight (95% adjusted CI -370, -74 g) and more often belonged to the LBW category (95% CI AOR 2.60--15.08) than non-coeliac controls. These infants were more often in the LBW category than infants whose mother suffered from non-diabetic autoimmune diseases (95% CI AOR 1.24--9.65). Coeliac disease in other relatives was not associated with any adverse effect on neonatal outcome. CONCLUSIONS: This study suggests that even treated coeliac disease, in either of the parents, has a negative effect on pregnancy, resulting in lower birth weight and perhaps shorter duration of pregnancy.

Reproductive life disorders in Italian celiac women. A case-control study

            (Martinelli, Fortunato et al. 2010) Download

BACKGROUND: The aim of this study is to explore the association between celiac disease and menstrual cycle, gestation and puerperal disorders. METHODS: The association between celiac disease and menstrual cycle, gestation and puerperal disorders in a sample of 62 childbearing age women (15-49 age) was assessed within an age and town of residence matched case-control study conducted in 2008. Main outcome measures were the presence of one or more disorders in menstrual cycle and the presence of one or more complication during pregnancy. RESULTS: 62 celiac women (median age: 31.5, range: 17-49) and 186 healthy control (median age: 32.5, range: 15-49) were interviewed. A higher percentage of menstrual cycle disorders has been observed in celiac women. 19.4% frequency of amenorrhea was reported among celiac women versus 2.2% among healthy controls (OR = 33, 95% CI = 7.17-151.8;, p = 0.000). An association has been observed between celiac disease and oligomenorrhea, hypomenorrhea, dysmenorrhea and metrorrhagia (p < 0.05). The likelihood of having at least one complication during pregnancy has been estimated to be at least four times higher in celiac women than in healthy women (OR = 4.1, 95% CI = 2-8.6, p = 0.000). A significant correlation has emerged for celiac disease and threatened abortion, gestational hypertension, placenta abruption, severe anaemia, uterine hyperkinesia, intrauterine growth restriction (p < 0.001). A shorter gestation has on average been observed in celiac women together with a lower birth weight of celiac women babies (p < 0.001). CONCLUSIONS: The occurrence of a significant correlation between celiac disease and reproductive disorders could suggest to consider celiac disease diagnostic procedures (serological screening) in women affected by these disorders.

Natural History of Potential Celiac Disease

            (Matuchansky 2011) Download

Gastrointestinal symptoms in children with type 1 diabetes screened for celiac disease

         (Narula, Porter et al. 2009) Download

BACKGROUND: The association between celiac disease (CD) and type 1 diabetes mellitus (DM) is recognized. Most cases of CD in patients with DM are reported to be asymptomatic. OBJECTIVES: The objectives of this study were to (1) compare and audit our practice with the published standards for screening for CD in children with DM, (2) characterize the children with DM and biopsy-confirmed CD, in terms of growth and gastrointestinal symptoms, and compare them with children with DM and negative celiac serology, and (3) document the effects of a gluten-free diet (GFD) after 1 year of gastrointestinal symptoms, growth, and insulin requirement. METHOD: We performed a retrospective case-note review of 22 children with DM, positive celiac serology +/- biopsy-confirmed CD, and 50 children with DM and negative celiac serology. RESULTS: Twenty-two children (3.9% of the total diabetic population) had positive celiac serology on screening, with 17 (3%) having biopsy-confirmed CD. Ninety-four percent of the children had standardized celiac serology testing. At diagnosis of CD, 13 of the 17 biopsy-positive children (76.4%) had > or =1 gastrointestinal symptom. The frequency of gastrointestinal symptoms in negative celiac serology diabetic children was 6% (3 of 50) (P < .0005). Symptoms resolved in all children after introduction of a GFD. A significant improvement in weight SD score (P = .008) and BMI SD score (P = .02) was noted in those compliant with a GFD after 1 year. CONCLUSIONS: Children with DM and CD have a higher frequency of gastrointestinal symptoms than their diabetic peers with negative celiac serology and are not truly asymptomatic. Institution of a GFD has a positive effect on nutritional status and symptom resolution in the short-term.


Type 1 diabetes mellitus and celiac disease: endothelial dysfunction

            (Picarelli, Di Tola et al. 2011) Download

Many reports indicate a hypercoagulative state in diabetes mellitus as result of endothelial damage. Experimental evidence suggests that a metabolic derangement triggers a cascade of biochemical events that lead to vascular dysfunction. The net effect is to convert the endothelium from thromboresistant to thrombogenic surface. In literature, a strong association between type 1 diabetes mellitus (DM1) and celiac disease (CD) has been reported. We do not have information about the hemostatic system in these associated conditions. Our study aims at evaluating whether the presence of CD in a group of DM1 patients is associated with a different expression of some hemostatic factors and with a different manifestation and/or progression of microvascular complications of DM1 in comparison with patients with only diabetes. Ninety-four adult DM1 patients were enrolled in the study and subsequently screened for CD. Anti-endomysial antibodies (EMA) were positive in 13 of 94 DM1 patients (13.8%). CD diagnosis was confirmed by histology and organ culture. The mean age and duration of DM1 of patients also affected by CD were similar to those of only diabetic patients, but the metabolic control and the hemocoagulative parameters were significantly different between the two groups: DM1 patients also affected by CD presented significantly lower concentrations of glycosylated hemoglobin (HbA1c) (P < 0.05), cholesterol (P < 0.001), triglycerides (P < 0.001), factor VII antigen (FVII:ag) (P < 0.005), factor VII coagulant activity (FVII:c) (P < 0.05), and prothrombin degradation fragments (F1+2) (P < 0.001), as well as higher values of activated C protein (APC) (<0.001). No retinal abnormalities and no signs of renal damage were observed in DM1 patients also affected by CD. Our results suggest a potential protective role of CD in the prothrombotic state of DM1.

Mean platelet volume could be a promising biomarker to monitor dietary compliance in celiac disease

            (Purnak, Efe et al. 2011) Download

Abstract Background. Celiac disease (CD) is an autoimmune disease that develops in patients with a genetic predisposition, incurring a susceptibility to gluten-containing foods such as barley, wheat, and rye. The elimination of gluten from the diet is the main therapeutic approach and usually leads to clinical and laboratory improvement. There are no ideal markers that objectively assess dietary compliance in CD patients. Materials and methods. Sixty newly diagnosed CD patients (male/female: 43/17) and 40 healthy subjects (male/female: 23/17) were enrolled in this study. The diagnosis of CD was established by both histological findings of duodenum biopsy (total villous atrophy and lymphocytic infiltration) and positive antibodies against endomysium or gliadin. Results. A significantly higher mean platelet volume (MPV) was observed in the CD group compared with healthy subjects (8.45 +/- 0.96 fL versus 7.93 +/- 0.63 fL; p = 0.004). After introduction of a gluten-free diet, the MPV of CD patients in the dietary adherent group was significantly lower than that of the non-adherent group (8.09 +/- 0.6 fL versus 8.9 +/- 1.08 fL; p = 0.001). Overall dietary adherence rate was 71.6% (43/60 CD patients). In the dietary compliant group, initiation of gluten-free diet was associated with a significant decrease in MPV from base-line values (8.56 fL versus 8.25 fL; p = 0.008). In the non-adherent group, MPV on 3-month follow-up was higher than at base-line (8.05 fL versus 8.91 fL; p = 0.001). Conclusion. MPV could be a promising and easily available biomarker for monitoring of dietary adherence in CD patients at a low cost in comparison with other modalities.

Home blood testing for celiac disease: recommendations for management

            (Rashid, Butzner et al. 2009) Download

OBJECTIVE: To provide recommendations for the management of patients who inquire about the Health Canada-approved, self-administered home blood tests for celiac disease or who present with positive test results after using the self-testing kit SOURCES OF INFORMATION: PubMed and the Cochrane Database of Systematic Reviews were searched from January 1985 to April 2008, using the subject headings diagnosis of celiac disease and management or treatment of celiac disease. Guidelines for serologic testing and confirmation of diagnosis of celiac disease by the American Gastroenterological Association and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition are used in this review. Level 1 evidence was used. MAIN MESSAGE: Although blood tests are helpful for screening purposes, the confirmatory test for celiac disease is a small intestinal biopsy. CONCLUSION: Patients whose blood tests for celiac disease provide positive results should have endoscopic small intestinal biopsies to confirm the diagnosis before starting a gluten-free diet.

Oral manifestations of celiac disease: a clinical guide for dentists

            (Rashid, Zarkadas et al. 2011) Download

Celiac disease (gluten sensitive enteropathy) is a common disorder affecting both children and adults. As many people with celiac disease do not present with the classic malabsorptive syndrome, delays in diagnosis are common. Dental enamel defects and recurrent aphthous ulcers, which may occur in patients with celiac disease, may be the only manifestation of this disorder. When dentists encounter these features, they should enquire about other clinical symptoms, associated disorders and family history of celiac disease. In suspected cases, the patient or family physician should be advised to obtain serologic screening for celiac disease and, if positive, confirmation of the diagnosis by intestinal biopsy. Dentists can play an important role in identifying people who may have unrecognized celiac disease. Appropriate referral and a timely diagnosis can help prevent serious complications of this disorder.

The incidence and clinical spectrum of refractory celiac disease in a north american referral center

            (Roshan, Leffler et al. 2011) Download

OBJECTIVES: Refractory celiac disease (RCD) is one of the most serious causes of persistent symptoms in patients with celiac disease (CD). Published reports suggest that approximately half of patients in Europe are RCD type II, which carries a poor prognosis with a 5-year survival rate of ~50% compared with ~90% for RCD type I. However, disease patterns may be different in North America. The aim of this study was to explore the clinical spectrum of RCD in a North American population. METHODS: Medical records of patients with biopsy-proven CD presenting to our institution were reviewed for a diagnosis of RCD. Demographic data, clinical characteristics, and mortality were evaluated and compared with our general CD population. RESULTS: In all, 34 out of 844 (4.0%) CD patients had RCD. The cumulative incidence of RCD for patients diagnosed with CD at our center was 1.5%. Unintentional weight loss at diagnosis of RCD was found in 76.5% (n=26) compared with 16.7% (n=141) at diagnosis of CD (P<0.0001) and diarrhea at diagnosis of RCD was found in 79.4% (n=27) compared with 40.5% (342) at diagnosis of CD (P<0.0001). Five patients (14.7%) were diagnosed with RCD type II and of these, two died of enteropathy-associated lymphoma within 24 months of diagnosis of CD (observed mortality rate 5.9%). CONCLUSIONS: Although RCD is a serious condition with significant morbidity; the observed mortality rates are low in our population. This study suggests that RCD may be less severe in North American vs. European populations.

Celiac disease and its effect on human reproduction: a review

            (Soni and Badawy 2010) Download

Celiac disease is an intestinal inflammatory disease that is triggered by gluten in the diet. Patients present with a wide array of symptoms due to malabsorption that include diarrhea, abdominal pain, bloating and weight loss. In women, this disease may have implications on menstrual and reproductive health. The symptom complex includes delayed menarche, early menopause, secondary amenorrhea, infertility, recurrent miscarriages and intrauterine growth restriction. These women benefit from early diagnosis and treatment. Therefore, celiac disease should be considered and screening tests performed on women presenting with menstrual and reproductive problems and treated accordingly. The objective of this article is to review the current literature on celiac disease and its association with the above-mentioned disorders.

A risk factor for female fertility and pregnancy: celiac disease

            (Stazi and Mantovani 2000) Download

Celiac disease is a genetically-based intolerance to gluten. In the past, celiac disease has been considered a rare disease of infancy characterized by chronic diarrhea and delayed growth. Besides the overt enteropathy, there are many other forms which appear later in life; target organs are not limited to the gut, but include liver, thyroid, skin and reproductive tract. It is now recognized that celiac disease is a relatively frequent disorder; the overall prevalence is at least 1:300 in Western Europe. Celiac disease may impair the reproductive life of affected women, eliciting delayed puberty, infertility, amenorrhea and precocious menopause. Clinical and epidemiological studies show that female patients with celiac disease are at higher risk of spontaneous abortions, low birth weight of the newborn and reduced duration of lactation. No adequate studies are available on the rate of birth defects in the progeny of affected women; however, celiac disease induces malabsorption and deficiency of factors essential for organogenesis, e.g. iron, folic acid and vitamin K. The overall evidence suggests that celiac disease patients can be a group particularly susceptible to reproductive toxicants; however, the pathogenesis of celiac disease-related reproductive disorders still awaits clarification. At present, like the other pathologies associated with celiac disease, the possible prevention or treatment of reproductive effects can only be achieved through a life-long maintenance of a gluten-free diet.

Celiac disease and pediatric type 1 diabetes: diagnostic and treatment dilemmas

            (Sud, Marcon et al. 2010) Download

Despite the advent of sensitive and specific serologic testing, routine screening for celiac disease (CD) in diabetic populations may not be universal practice, and many clinicians struggle to find the optimal approach to managing CD in pediatric Type 1 diabetes (T1D) patients. While some clinicians advocate screening for CD in all patients with T1D, others are unsure whether this is warranted. The diagnosis of patients who present with symptomatic CD, including malabsorption and obvious pathology upon biopsy, remains straightforward, with improvements noted on a gluten-free diet. Many patients identified by screening, however, tend to be asymptomatic. Evidence is inconclusive as to whether the benefits of screening and potentially treating asymptomatic individuals outweigh the harms of managing a population already burdened with a serious illness. This review focuses on current knowledge of CD in children and youth with T1D, highlighting important elements of the disease's pathophysiology, epidemiology, clinical presentation, and diagnostic challenges.

Celiac disease is not a risk factor for infertility in men

            (Zugna, Richiardi et al. 2011) Download

OBJECTIVE: To examine fertility in men with biopsy-verified celiac disease (CD) in light of research that suggests that men with CD have impaired sperm quality. DESIGN: Using multinomial logistic regression and Cox regression, we estimated the fertility of the study group compared with that of 31,677 age-matched reference male controls. SETTING: Sweden. PATIENT(S): Swedish nationwide population-based cohort of 7,121 men with CD (defined according to duodenal-jejunal biopsy data with [Marsh III] villous atrophy) ages 18-54 years at some point before the end of follow-up. MAIN OUTCOME MEASURE(S): Number of children according to the Swedish Multi-Generation Register. RESULT(S): During follow-up, men with CD had 9,935 children compared with 42,245 among controls. Adjusting for age, calendar period, and parity and stratifying by education, the overall fertility hazard ratio in the men with biopsy-verified CD was 1.02 (95% confidence interval, 0.99-1.04). CONCLUSION(S): This study found a normal fertility in men with diagnosed CD.


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