Subclinical Celiac Disease Research Articles

Nutritional status, growth and disease management in children with single and dual diagnosis of type 1 diabetes mellitus and coeliac disease.

BackgroundThe consequences of subclinical coeliac disease (CD) in Type 1 diabetes mellitus (T1DM) remain unclear. We looked at growth, anthropometry and disease management in children with dual diagnosis (T1DM + CD) before and after CD diagnosis.MethodsAnthropometry, glycated haemoglobin (HbA1c) and IgA tissue transglutaminase (tTg) were collected prior to, and following CD diagnosis in 23 children with T1DM + CD. This group was matched for demographics, T1DM duration, age at CD diagnosis and at T1DM onset with 23 CD and 44 T1DM controls.ResultsNo differences in growth or anthropometry were found between children with T1DM + CD and controls at any time point. Children with T1DM + CD, had higher BMI z-score two years prior to, than at CD diagnosis (p < 0.001). BMI z-score change one year prior to CD diagnosis was lower in the T1DM + CD than the T1DM group (p = 0.009). At two years, height velocity and change in BMI z-scores were similar in all groups. No differences were observed in HbA1c between the T1DM + CD and T1DM groups before or after CD diagnosis. More children with T1DM + CD had raised tTg levels one year after CD diagnosis than CD controls (CDx to CDx + 1 yr; T1DM + CD: 100% to 71%, p = 0.180 and CD: 100% to 45%, p < 0.001); by two years there was no difference.ConclusionsNo major nutrition or growth deficits were observed in children with T1DM + CD. CD diagnosis does not impact on T1DM glycaemic control. CD specific serology was comparable to children with single CD, but those with dual diagnosis may need more time to adjust to gluten free diet.

Subclinical celiac disease presented with postpartum low-back pain: case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Pediatric and adult celiac disease: similarities and differences

Differences between children and adults in celiac disease (CD) presentation and epidemiology are reviewed here. Clinical manifestations, histological changes, serology, and response to gluten-free diet are similar. Differences exist in epidemiology, type of clinical presentations, coexisting diseases, complications, and association with obesity. CD is two to five times more common in children than in adults. Classical CD with gastrointestinal symptoms is more common in children whereas nonclassical CD dominates in adults. A gene dose phenomenon (double-dose HLA-DQB1 02 allele) is postulated to be responsible for this difference. Coexisting autoimmune diseases like diabetes mellitus type 1, Sjogren's syndrome, and dermatitis herpetiformis are more common in adults than in children (42 % vs. 5 %). The association of overweight/obesity and CD is stronger in adults than in children (22.5 % vs. 14 %). Besides poor compliance, pancreatic insufficiency, bacterial overgrowth, lactose intolerance, irritable bowel syndrome, lymphocytic colitis, and microscopic colitis are considered responsible for nonresponsive CD in adults but not in children. Complications like refractory sprue and small intestinal neoplasms are seen exclusively in adults. Existing diagnostic criteria (modified ESPGHAN) are not suitable for diagnosing CD in adults as the majority of cases are either nonclassical or subclinical CD.

Letter: complications of coeliac disease despite a gluten‐free diet

In their recent paper, Lebwohl and colleagues report an interesting finding: persistent villous atrophy (VA) does not seem to be associated with increased mortality in coeliac disease (CD).1 This conclusive statement is quite surprising. As already stated by the authors, CD patients are at risk of earlier death,2, 3 and failure in mucosal healing has been thought to be the main factor.4, 5 This study seems to call into question this consolidate hypothesis, and it deserves some comments from a clinical practice's point of view. We know that histological recovery takes different times, according to the age when gluten-free diet (GFD) has started. In our experience, subdividing the patients according to age, only the younger patients (5–30 years) showed significant improvement of histology within 12 months (P < 0.034); older patients (>30 years) showed histological improvement, but this was not statistically significant, even after 24 months on a GFD.6 Gluten-free diet is generally advised to CD patients for three main reasons: treating symptoms related to the disease; preventing immunological gluten-related disorders; and preventing neoplastic complications. GFD and adherence to diet are considered the key factors in obtaining mucosal healing and in preventing occurrence of complications.7, 8 In our experience, the time to the occurrence of complications with GFD seems to be related to type of disease rather than to the severity of the histological lesion at the time of the diagnosis. In fact, considering the time of appearance of complications after GFD had started, complications occurred after a mean/median time with GFD of 6.5/5 years [standard deviation (s.d.) ± 5.08] in classical CD, and after a mean/median time of 3.5/4 years (s.d. ± 1) in subclinical CD. However, looking at the compliance to GFD in patients developing complications, we found that 6/14 (42.9%) patients with classical CD were not fully compliant with GFD, whilst 2/4 (50%) of subclinical CD were not fully compliant (P = n.s.).9 In light of our and Lebwohl's experience, should a GFD still be advised to prevent complications? Despite the retrospective design, Lebwohl's study calls into question whether and why an increased complication rate (increased mortality rate included) occurs in CD. Furthermore, confirmative and prospective studies are, therefore, welcomed. Declaration of personal and funding interests: None.

Type 1 diabetes and celiac disease: The effects of gluten free diet on metabolic control

Type 1 diabetes mellitus is associated with celiac disease, with a prevalence that varies between 0.6% and 16.4%, according to different studies. After a diagnosis of celiac disease is confirmed by small bowel biopsy, patients are advised to commence a gluten-free diet (GFD). This dietary restriction may be particularly difficult for the child with diabetes, but in Europe (and in Italy) many food stores have targeted this section of the market with better labeling of products and more availability of specific GFD products. Treatment with a GFD in symptomatic patients has been shown to improve the symptoms, signs and complications of celiac disease. However, the effects of a GFD on diabetic control are less well established. Initial reports of improved hypoglycemic control were based on children who were diagnosed with celiac disease associated with malabsorption, but there have subsequently been reports of improvement in patients with type 1 diabetes with subclinical celiac disease. There are other studies reporting no effect, improved control and an improvement of hypoglycemic episodes. Moreover, in this review we wish to focus on low glycemic index foods, often suggested in people with type 1 diabetes, since they might reduce postprandial glycemic excursion and enhance long-term glycemic control. In contrast, GFD may be rich in high glycemic index foods that can increase the risk of obesity, insulin resistance and cardiovascular disease, worsening the metabolic control of the child with diabetes. Hence, it is important to evaluate the impact of a GFD on metabolic control, growth and nutritional status in children with type 1 diabetes.

Subclinical Celiac Disease and Crystal-Induced Kidney Disease Following Kidney Transplant

Decreased kidney function from kidney deposition of calcium oxalate has been described previously in inflammatory bowel disease and after jejuno-ileal and Roux-en-Y gastric bypass surgeries. Although celiac disease is the most prevalent bowel abnormality associated with intestinal malabsorption, its relationship to high kidney oxalate burden and decreased kidney function has not been established. We report a case of subclinical celiac disease and hyperoxaluria that presented with loss of kidney function as a result of high oxalate load in the absence of overt diarrhea, documented intestinal fat malabsorption, and nephrolithiasis. Subclinical celiac disease is commonly overlooked and hyperoxaluria is not usually investigated in kidney patients. We propose that this entity should be suspected in patients with chronic kidney disease in which the cause of kidney damage has not been clearly established.

Revisiting the risk of celiac disease in children born small for gestational age: A sibling design perspective

Objective. An association between small for gestational age (SGA) and risk for celiac disease (CD) in childhood has previously been reported. However, this association may reflect residual confounding by genetic or environmental factors. For example, presence of subclinical CD in the mother might be a common cause of both SGA and CD in the offspring. We investigate whether SGA is causally associated with CD before age six years by applying both conventional population-based regression models and sibling analysis that investigates the association in siblings discordant for SGA. Material and methods. Using the Swedish Medical Birth Registry, we identified all singleton children born in Sweden during 1987–1993 (792,401). Of these we included 681,954 children in the study and identified 2641 cases of CD using the Swedish National In-Hospital Registry. We applied both conventional Cox regression analysis and a quasi-experimental sibling design that to some extent simulates a counterfactual situation of exposure, reducing possible confounding effects of genetic and shared environmental factors. Results. We identified an increased risk of CD in both boys (hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.25–2.32) and girls (HR 1.30, 95% CI 0.99–1.70) using conventional Cox regression models. Using sibling analysis, the association between SGA and CD was confirmed in boys (HR 4.23, 95% CI 1.19–15.04) but not in girls (HR 1.00, 95% CI 0.45–2.20). Conclusions.Our results support a causal association between SGA and CD risk in boys but not in girls, although the mechanisms underlying this difference are still unclear.

Systemic and neurologic autoimmune disorders associated with seizures or epilepsy

In this article, we review the incidence and significance of seizures in well-established autoimmune disorders, including multiple sclerosis (MS), diabetes mellitus, celiac disease, thyroid disease, and systemic lupus erythematosus (SLE). The five following presentations discuss the incidence and possible pathogenesis of epilepsies that are found in these well-known autoimmune conditions. There is a large body of evidence describing the clinical presentation of seizures with MS and SLE, and showing that refractory epilepsy can complicate these already challenging disorders. However, the mechanisms involved are complex and generally not well understood. Neurologic syndromes, including seizure disorders, can also be a feature of celiac disease (CD) or subclinical CD, sometimes associated with cerebral calcification. The association between type-1 diabetes mellitus (T1DM) and epilepsy is unclear and requires more definitive epidemiologic analysis, despite the fact that antibodies to glutamic acid decarboxylase may provide a link between the two conditions. The association between thyroid disorders and encephalopathies, often termed Hashimoto's encephalopathy, is well known but the pathogenic significance of antithyroid antibodies in this condition is still debated. In general, the relationships between autoimmune mechanisms and seizures in these conditions are unclear; the seizures are likely to be caused by a variety of mechanisms, including ischemia, neuronal damage, and specific and nonspecific immunity.

Subclinical celiac disease and gluten sensitivity.

Atypical presentation is the most common form of celiac disease (CD). Although the terminologies like latent, silent and potential have expressed different aspects of clinical and pathological behaviour of CD, they also have contributed in some extent to confusion between clinicians and patients due to the multiple definitions and uncertainty around them. In the light of new advances and the discovery of entities such as non-celiac gluten sensitivity, using subclinical instead of silent and atypical instead of potential/latent may simplify the understanding behind the clinical behaviour of atypical CD. The evidence behind a lower threshold for starting a gluten free diet (GFD) in non-celiac gluten sensitive patients would strongly support applying a GFD treatment strategy in any forms of CD.

Association Between Psoriasis and Coeliac Disease? A Case-control Study

The first published data concerning a possible relationship between psoriasis and pathologies of the gastrointestinal tract appeared as long as 30 years ago (1, 2), and subsequently there have been numerous reports on psoriasis and coeliac disease (3-5). These reports have included investigations into the presence of antibodies specific to coeliac disease in patients with psoriasis compared with controls. The findings demonstrated, in some cases, no correlation (6-8), but in others the presence of high titre in the IgA antibodies anti-gliadin, anti-reticulin, anti-endomysium and tissue anti-transglutaminase (9, 10). Furthermore, the presence of these antibodies and their increase was linked to a greater severity in the skin pathology (4). There have also been reports of patients with extensive psoriasis lesions and positivity for anti-gliadin, whose skin lesions regressed significantly after following a gluten-free diet for 3—6 months only to reappear on stopping the diet (11). In particular, it was also found that using a gluten-free diet as sole therapy in patients with psoriasis, who were positive for anti-gliadin and with high transglutaminase titres, improvement in skin lesions occurred along with a reduction in transglutaminase titre (12). As regards the pathogenetic mechanism behind this possible association, little is known, although there have been diverse hypotheses (3, 13): (i) the anomalous intestinal permeability in people with coeliac disease could represent a trigger factor for psoriasis; (ii) in coeliac disease gliadin induces a sensibilization of T cells, and their activation could be associated with the pathogenesis of the cutaneous lesions; (iii) psoriasis lesions in people with coeliac disease could be related to vitamin D deficiency, a characteristic of both diseases. Because in Sardinia there is a high prevalence of subclinical coeliac disease (14), we performed a case-control study to evaluate a possible association between this disease and psoriasis.

Latent celiac disease in reproductive performance of women

To investigate the prevalence of positive serologic findings for celiac disease in Indian women with poor reproductive performance. Cross-sectional except that the women with intrauterine growth restriction were followed prospectively until delivery. Department of Obstetrics and Gynecology of a tertiary teaching hospital, New Delhi. 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). None. The presence of antigliadin IgA and IgG, anti-tissue transglutaminase IgA by ELISA, and IgA antiendomysium antibody by indirect immunofluorescence microscopy. 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. Women having poor reproductive performance had subclinical celiac disease. The serology for celiac disease can be considered in idiopathic cases.

The Hydrogen Breath Test: New Uses for an Old Test

The Hydrogen Breath Test: New Uses for an Old Test

Chronic Urticaria and Celiac Disease: A Case Report

We describe a case of a 9-year-old girl who presented chronic urticaria associated with celiac disease. The prevalence of the manifestation of chronic urticaria in celiac disease is unknown but increase in atopic immunologic disorders has been reported in the setting of gluten enteropathy. Relationship between the clinical manifestations is not clear. The present case of subclinical celiac disease diagnosis in an otherwise asymptomatic child with chronic urticaria further reinforces the evidence that differential for celiac disease warrants to be always considered in children with refractory urticaria.

Serological screening for coeliac disease in adults with Turner's syndrome: prevalence and clinical significance of endomysium antibody positivity

ObjectiveTo investigate the prevalence of coeliac disease (CD) in an adult population with Turner's syndrome (TS).DesignA clinic population with TS was screened using a serological test for CD.MethodsTwo hundred and fifty six patients with TS were included in the study. Five patients had existing diagnoses of CD. The remaining 251 asymptomatic patients were screened using an IgA endomysium antibody (EMA) test. Positive cases were offered endoscopy with duodenal biopsy. HLA typing was undertaken in existing cases and new EMA-positive cases.ResultsOf the 251 patients screened, eight were found to be EMA positive (3.2%). Seven patients proceeded to duodenal biopsy on which all were confirmed histologically to have CD (2.8%). The prevalence of subclinical CD in the population can therefore be estimated between 2.8 and 3.2%. The total population prevalence of CD, including the previously diagnosed cases, is estimated between 4.7 and 5.1%. Ten patients with histologically confirmed CD underwent HLA typing of which eight were HLA-DQ2 positive, one was HLA-DQ8 positive and one was negative to both HLA-DQ2 and HLA-DQ8.ConclusionsThis study demonstrates an increased prevalence of CD in an adult population with TS over the general population. This is consistent with previous data published in paediatric populations.

Complications in Celiac Disease Under Gluten-Free Diet

We assessed the onset of malignant and nonmalignant complications in a cohort of celiac disease (CD) patients under gluten-free diet (GFD). Five hundred and forty-nine CD patients were retrospectively assessed. Two hundred and fifty-one (45.7%) showed classical, 262 (47.7%) subclinical, and 36 (6.6%) silent form of CD at the time of the diagnosis. The mean time under GFD was 7.13 years (range 1-15 years). Out of 549 patients, 381 (69.4%) were fully compliant, 112/549 (20.4%) reported less than one dietary transgression/month, and 56/549 (10.2%) reported at least one dietary transgression/month. Out of 549 patients, 18 (3.3%) patients developed complications under GFD (seven malignant and 11 nonmalignant complications). Fourteen patients were previously affected by classical CD (5.6% of the overall patients with classical CD), and four were affected by subclinical CD (1.5% of the overall patients with subclinical CD). None of the patients affected by silent CD developed complications. There was no statistical difference between the mean age of the two groups developing complications (P = n.s.). Complications appeared after a mean time under GFD of 6.5 years in classical CD, and after a mean time of 3.5 years in subclinical CD (P = n.s.). Finally, 6/14 (42.8%) patients with classical CD were not fully compliant to GFD, while 2/4 (50%) of subclinical CD patients were not fully compliant to GFD (P = n.s.). Less than 5% of CD patients may develop complications under GFD. Complications seem to affect more classical CD than subclinical CD, and seem to be irrespective of optimal GFD adherence.

Urinary Stone Disease in Adults With Celiac Disease: Prevalence, Incidence and Urinary Determinants

Intestinal diseases may cause urinary stone disease via hyperoxaluria or diarrhea induced hyperconcentrated acidic urine. Data are missing on urinary stone disease in celiac disease, a common malabsorptive disorder. In this study we analyzed urinary stone disease and urine composition in adults with celiac disease. Study patients were 18 years or older, untreated, and newly diagnosed with celiac disease by serum markers and jejunal biopsy. Clinical presentation of celiac disease was assessed focusing on 5 disorders of diarrhea, and deficiency of calorie (low body mass index or weight loss), lipid (low prothrombin time or low serum lipids), iron (low hemoglobin or low serum ferritin) and calcium (low serum calcium or low bone densitometry). Urinary stone disease history was assessed by questionnaire (imaging, stone excretion, stone disruption/removal). Urinary variables were measured in a 24-hour collection in a subgroup of patients. Under untreated conditions (baseline) urinary stone disease was independent of celiac disease presentation and more prevalent in patients with celiac disease than in a population sample used as a control (608 and 3,540, 7.9% and 5.0%, sex and age adjusted odds ratio 4.0, 95% CI 2.7-5.9). Excluding from analysis individuals with baseline urinary stone disease, the incidence of urinary stone disease history was not significantly different between the treated celiac disease (gluten-free diet) and control population (458 and 3,003, 2.4% vs 3.9%). The urine of untreated patients with celiac disease differed from that of healthy volunteers with 120% higher oxalate and 43% lower calcium (in 45 and 45, p <0.001). A gluten-free diet corrected urinary abnormalities (p <0.01). Urinary stone disease risk is high in untreated patients with celiac disease independent of overt malabsorption. Hyperoxaluria is likely the underlying disorder. A gluten-free diet reduces urinary stone disease risk and oxaluria.

Review: Gluten and glucose management in type 1 diabetes

The prevalence of coeliac disease in patients with type 1 diabetes is significantly increased when compared to the general population. Ancompared to the general population. An explanation of the association between the development of both diseases may be explained by the inheritance of common major histocompatibility complex immunogenotypes that influence the presentation of auto antigens to CD4+ T-Cells. The subsequent loss of self tolerance results in destruction of the small bowel villi and pancreatic β-cells in coeliac and type 1 diabetes respectively. The diagnosis of coeliac disease in type 1 diabetic patients occurs commonly as a result of screening of individuals with subclinical coeliac disease. Recent studies have demonstrated the clinical benefit of treating subclinical coeliac disease in children with improvement in growth parameters, resolution of anaemia and fewer hypoglycaemic episodes. There is no current clinical evidence supporting routine screening of adult type 1 diabetic patients for coeliac disease. After the diagnosis of coeliac disease, type 1 diabetic patients should be commenced on a gluten-free diet with care co-ordinated between a dietician, gastroenterologist anddiabetologist.

Mesentric vein thrombosis as a presentation of subclinical celiac disease

Mesentric vein thrombosis as a presentation of subclinical celiac disease

Abnormal Intestinal Permeability in Primary Biliary Cirrhosis

Antimitochondrial antibodies (AMAs) found in patients with primary biliary cirrhosis (PBC) cross-react with bacterial proteins and hence molecular mimicry has been proposed as a mechanism for AMA development. Alterations in gastrointestinal permeability would provide a potential route for increased exposure of gut flora to the immune system. In this study we aimed to compare the measured gastrointestinal permeability in patients with PBC to that in patients with liver disease (hepatitis C) and healthy control populations. Subjects drank a mixture of sucrose, lactulose, and mannitol dissolved in water. Eight-hour urinary excretion of the sugars was measured to assess intestinal permeability. Antiendomysial antibody testing was performed to exclude subclinical celiac disease. Eighty-six patients with PBC were evaluated and compared to 69 hepatitis C patients and 155 healthy controls. The mean urinary excretion of sucrose in the PBC patients (133.89 +/- 72.56 mg) was significantly higher than that in hepatitis C patients (101.07+/-63.35) or healthy controls (89.46+/-41.76) (P=0.0001), suggesting abnormal gastric or proximal small intestinal permeability. Sucrose excretion was not increased among patients with hepatitis C compared to healthy controls. The ratio of lactulose:mannitol excretion, reflecting small bowel permeability, was also elevated in the PBC group (0.017+/-0.012) compared to healthy controls (0.012+/-0.007) (P=0.0001) but was equal to that found among patients with hepatitis C (0.016+/-0.011) (P=NS). We conclude that the permeability of both the stomach and the small bowel is increased in patients with PBC, however, it is unclear if it is a cause, consequence, or manifestation of the disease.

Autoantibodies in Argentine Women with Recurrent Pregnancy Loss

To determine the presence or absence of subclinical autoimmunity in Caucasian Argentine healthy women with first trimester recurrent pregnancy loss (RPL), the sera of 118 healthy women with a history of three or more consecutive abortions and 125 fertile control women without abortions and two children were analyzed for the presence of autoantibodies: immunoglobulin (Ig)G and IgM anticardiolipin, antinuclear (ANA), antismooth muscle (ASMA), antimitocondrial (AMA), antiliver-kidney-microsomal fraction (LKM), antigastric parietal cells (GPC), antineutrophil cytoplasmatic (ANCA) and antibodies antigliadin type IgA and IgG and IgA antitransglutaminase related with celiac disease (CD). ANA, ASMA, AMA, anti-LKM, antibodies to GPC and ANCA were determined by indirect immunofluorescence (IFI) and anticardiolipin, antigliadina and antitransglutaminase antibodies were measured by enzyme-linked immunosorbent assays (ELISA). There was no significant difference between controls and patients with ANA, ASMA, AMA, LKM, ANCA and GPC. The prevalence of anticardiolipin antibodies in RPL was significantly higher than controls (P < 0,01) and the prevalence of positive antibodies for antigliadina type IgA and IgG and IgA antitransglutaminase in RPL was significantly higher than controls (P < 0.04). We show that Caucasian Argentine women with RPL showed significantly higher incidence of anticardiolipin antibodies than normal controls and finally we recommended the screening of IgA and IgG antigliadina and IgA antitransglutaminase antibodies in pregnancy, because of the high prevalence of subclinical CD in RPL and the chance of reversibility through consumption of a gluten free diet.