Subclinical Celiac Disease Research Articles

Beyond diagnosis: exploring coeliac disease incidence alongside clinical and laboratory characteristics of newly diagnosed children in Slovenia.

Coeliac disease is characterized by a wide array of clinical presentations. The focus of our study was to comprehensively assess the clinical manifestations of coeliac disease in newly diagnosed children in Slovenia. Our objectives include estimating the incidence of the disease in children in 2022. In this prospective study, Slovenian paediatric gastroenterologists were invited to provide patient data using medical records of children under 19 diagnosed with coeliac disease from March 2021 to October 2023. Patient data were collected through a dedicated web-based form adapted from the CD SKILLS project, including data on clinical manifestations and laboratory results. Furthermore, the study included an estimation of the incidence of coeliac disease in children and adolescents in Slovenia in 2022. Analysis involved data from 160 children and adolescents (median age: 8 years; 61.9% female). Overall, 16.9% were asymptomatic at diagnosis and 29.4% belonged to a high-risk group for coeliac disease. Among symptomatic cases ( N = 133), abdominal pain was the leading symptom (44.4%), followed by anaemia (12.0%) and diarrhoea (10.5%). Malabsorption symptoms were more prevalent in very young children. Anaemia was found in 22.8 and 10.7% had abnormal alanine aminotransferase levels. The estimated incidence of coeliac disease in Slovene children in 2022 was 17.5/100 000. Abdominal pain emerged as the primary symptom of coeliac disease in children and adolescents, except in very young children where malabsorption symptoms were predominant. Our observation of a lower prevalence of abnormal liver function tests suggests subclinical coeliac disease may be less common in children. Moreover, the calculated coeliac disease incidence in Slovenia aligns with existing data.

S1562 Subclinical Celiac Disease in the U.S. Hispanic Population: Results From the Los Angeles County Department of Health Services

Introduction: Anemia is a common extraintestinal manifestation of celiac disease (CeD). Although perceived as a predominantly White disease with a 1% prevalence, CeD also affects other underreported populations, such as the Hispanic population. We aimed to estimate the prevalence of CeD in Hispanic patients presenting with unexplained anemia. Methods: A cross-sectional study was completed through a clinical management database and electronic medical record after receiving Institution Review Board approval. Adult Hispanic patients with unexplained anemia who underwent upper endoscopy with duodenal biopsies between 2013 and 2020, were included. This study was conducted at the Los Angeles County Department of Health Services, a safety-net public health care system with a predominantly Hispanic (65%) population. Electronic medical records were queried for the diagnosis of biopsy-proven CeD. Results: Two hundred six subjects underwent upper endoscopy for unexplained anemia, of which 61 were excluded (18 underwent an upper endoscopy without biopsy, 7 were non-Hispanic, and 36 patients had normal hemoglobin levels; Table). Among all Hispanic patients referred for endoscopic evaluation of unexplained anemia (N = 145), the mean age was 53.9 years, and 66% were female. The overall prevalence of biopsy-proven CeD was 4.8% (N = 7/145). In patients with iron-deficiency anemia (IDA) specifically, the prevalence of CeD was 4.5% (N = 3/67). Of the 7 patients with confirmed CeD, only one in retrospect had associated diarrhea. None of the patients had a family history of CeD. Interestingly, only one of 5 tested patients had positive IgA tissue transglutaminase antibody, and the remainder were seronegative. Other CeD-related laboratory testing including vitamin B12 and liver function tests were unremarkable; thyroid stimulating hormone (TSH) levels were within normal range except for one patient with elevated levels due to poorly controlled hypothyroidism. Conclusion: The prevalence of CeD in adult Hispanic patients with unexplained anemia (unspecified or IDA) is similar to the prevalence in White patients, a finding not previously reported in the literature. Screening for CeD in patients with unexplained anemia in general, and IDA specifically, is of value in Hispanic patients as well as White ones. Seronegative CeD requires endoscopic evaluation with duodenal biopsies for diagnosis. Table 1. - Clinical and Lab Characteristics of Patients with Biopsy-Confirmed Celiac Disease tTG: IgA tissue transglutaminase within <4 months from index endoscopy; TSH: thyroid stimulating hormone; M: male; F: female; AST: aspartate aminotransferase; ALT: alanine transaminase ID Hemoglobin (Ferritin) AST/ALT Total Bilirubin IgA tTG Vitamin B12 TSH Other Comorbidities 49 F 8.5 33/17 0.5 None 652 12.8 Hypothyroidism, Rheumatoid arthritis on sulfasalazine and methotrexate 42 F 11.6 (70.7) None None < 1 596 None Refractory GERD s/P fundoplication 57 F 8.4 (7.6) 42/51 0.6 >100 NA None Hypothyroidism, Chronic hepatitis C 34 F 11.7 16/12 0.6 < 1 325 None None 40 M 10.7 29/40 0.6 None 481 0.83 Substance abuse, Coronary artery disease with NSTEMI, Osteoporosis 50 F 9.9 (5.4) 22/23 0.5 < 1 291 2.1 Stage II breast cancer 44 F 9.5 (3.1) 29/33 0.6 < 1 NA 1 Type II diabetes

Celiac disease in duodenal biopsies; 2 year experience at a tertiary care hospital

Background: Duodenal endoscopic biopsy is a common useful test advised for patients presenting with various malabsorption syndromes. Aim: To study the histopathological changes observed in suspected malabsoption cases including Celiac disease (CD) with emphasis upon the Intraepithelial Lymphocytes (IELs) and to have a clinico-pathologic correlation. Settings & Design: This was a 2 year prospective study of cases presenting to gastrology OPD with suspected malabsorption selected for duodenal biopsy. Materials and Methods : Haematoxylin and Eosin (H&E) stain was used for study of histological parameters. IEL counts were correlated in CD3 immunohistochemical (IHC) stain. Clinical and laboratory parameters were correlated wherever available. Statistical Analysis: The variables were expressed as mean SD. Chi - square test or independent T test was used for comparison of variables. p value was < 0> Results: Out of 164 duodenal biopsies,105 cases had raised IEL.11 patients had CD (10.47%), rest were non celiac disease (NCD) of differen t aetiologies.Liver function tests, Endoscopy, Architecture of mucosa, crypt architecture, blunting, villous crypt ratio showed statistically significant correlation between CD and nonceliac disease groups with p values (P~0.034), (P~0.000),P~0.002),(P~0.000), (P~0,000) and (P~0.000) respectively. The specificity and positive predictive value (PPV) of villous tip IEL in both H&E & CD3 IHC were 100% in CD cases in our study. Conclusion: A complete clinical, endoscopic, serological and histopathological evaluation is essential for diagnosis of CD cases. Raised IEL in duodenal biopsies can be a very useful initial indicator for detecting many latent or subclinical CD cases. Keywords: Biopsy, Celiac Disease, Intraepithelial lymphocytes, Malabsorption.

Effect of Gluten-FREE Diet on Metabolic Control and Anthropometric Parameters in Type 1 Diabetes with Subclinical Celiac Disease: A Randomized Controlled Trial

Objective: It is unclear whether the institution of gluten-free diet (GFD) is beneficial in patients with type 1 diabetes (T1DM) and subclinical celiac disease (CD). Our primary objective was to evaluate the effect of GFD on the frequency of hypoglycemia, in patients with T1DM and subclinical CD. Our secondary objective was to investigate the effect of GFD on height, weight, glycosylated hemoglobin (HbA1c), insulin dose requirement, and bone mineral homeostasis. Methods: We carried out a prospective open label randomized controlled trial (RCT). Patients with T1DM and subclinical CD were randomized to receive GFD or a normal diet for 1 year. The primary outcome was the frequency of hypoglycemic episodes (blood glucose <70 mg/dL) measured by self-monitoring of blood glucose (SMBG) at the sixth month of the study in the 2 groups. Results: Screening for CD was carried out in 320 T1DM patients. Thirty eligible patients were randomized to receive GFD (n = 15) or a normal diet (n = 15). The mean number of hypoglycemic episodes/month recorded by SMBG and the mean time spent in hypoglycemia measured by CGM (minutes) in the GFD group versus the non-GFD group at six months was 2.3 minutes versus 3.4 minutes (P = .5) and 124.1 minutes versus 356.9 minutes (P = .1), respectively. The mean number of hypoglycemic episodes/month significantly declined in the GFD group (3.5 episodes at baseline versus 2.3 episodes at the sixth month; P = .03). The mean HbA1c declined by 0.73% in the GFD group and rose by 0.99% in non-GFD group at study completion. Conclusion: This is the first RCT to assess the effect of GFD in T1DM and subclinical CD. A trend towards a decrease in hypoglycemic episodes and better glycemic control was seen in patients receiving GFD. Abbreviations: BMC = bone mineral content; BMI = body mass index; CD = celiac disease; CGM = continuous glucose monitoring; GFD = gluten-free diet; Hb = hemoglobin; HbA1c = glycosylated hemoglobin; iPTH = intact parathyroid hormone; RCT = randomized controlled trial; SMBG = self-monitoring of blood glucose; T1DM = type 1 diabetes mellitus; tTG-IgA = tissue transglutaminase immunoglobulin A.

Current Concepts of Dermatitis Herpetiformis.

Dermatitis herpetiformis (DH) is an autoimmune skin disease that causes itchy, blistering rash, typically on the elbows, knees and buttocks. DH and coeliac disease share the same genetic background, glutendependent enteropathy and antibody response against tissue transglutaminase. DH is currently considered a cutaneous manifestation of coeliac disease, and the prevailing hypothesis is that DH develops as a late manifestation of subclinical coeliac disease. The incidence of DH is decreasing contemporarily with the increasing incidence of coeliac disease. The IgA immune response in DH skin is directed against epidermal transglutaminase, while the autoantigen in the gut is tissue transglutaminase. Granular IgA deposition in the papillary dermis is pathognomonic for DH, and is a finding used to confirm the diagnosis. The treatment of choice for DH is a life-long gluten-free diet, which resolves the rash and enteropathy, increases quality of life, and offers a good long-term prognosis.

High Prevalence of Celiac Disease in Patients with Immune Thrombocytopenia.

Celiac disease (CD) is known to be associated with several autoimmune disorders. We studied the prevalence of subclinical CD among patients with immune thrombocytopenia (ITP) as compared to general population. Cases of primary ITP between the age group of 18-60years were studied. Besides clinical examination, all patients underwent serology testing for tissue transglutaminase antibody (tTG) IgA and anti-endomysial antibodies IgA. The diagnosis of CD was made if both antibodies were positive. Healthy subjects acted as controls and underwent serological testing for tTG IgA. Seventy-nine primary ITP and 316 healthy subjects underwent serology testing for CD. Four patients of primary ITP (4/79) were positive for both serology as compared to 2 (2/316) healthy controls [odds ratio 8.37 (CI 1.50-46.47, p < 0.005)]. Among the ITP cases only one had clinical symptoms of CD while none of the healthy controls had symptoms of CD. There is a significantly higher prevalence of subclinical CD in patients with ITP. Since the prevalence of CD is known to vary among different geographical zones, we suggest further studies on screening of ITP patients for CD in areas of high prevalence.

Celiac Disease Prevalence Is Increased in Primary Sjögren’s Syndrome and Diffuse Systemic Sclerosis: Lessons from a Large Multi-Center Study

Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p < 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p ≤ 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc–CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis.

Iron-deficiency anemia as a subclinical celiac disease presentation in an Argentinian population.

There is a wide heterogeneity in the reports of celiac disease prevalence in iron-deficiency anemia patients. To determine the prevalence of celiac disease in patients with iron-deficiency anemia. Adult patients with a diagnosis of iron-deficiency anemia were enrolled for upper endoscopy with duodenal biopsies. Healthy volunteers that underwent upper endoscopy were enrolled as controls. A total of 135 patients with iron-deficiency anemia and 133 controls were enrolled. Celiac disease prevalence was higher in the iron-deficiency anemia group [11.11 vs. 1.51%, OR: 8.18 (1.83-36.55), P=.001). Of the celiac disease patients in the iron-deficiency anemia group, 73.3% had at least one endoscopic sign suggesting villous atrophy, whereas 100% of the celiac disease patients in the control group presented with at least one endoscopic sign. Patients with iron-deficiency anemia have an increased risk for celiac disease. Up to 25% of these patients may not present any endoscopic sign suggesting villous atrophy.

Iron-deficiency anemia as a subclinical celiac disease presentation in an Argentinian population

BackgroundThere is a wide heterogeneity in the reports of celiac disease prevalence in iron-deficiency anemia patients. AimTo determine the prevalence of celiac disease in patients with iron-deficiency anemia. Materials and methodsAdult patients with a diagnosis of iron-deficiency anemia were enrolled for upper endoscopy with duodenal biopsies. Volunteers that underwent upper endoscopy were enrolled as controls. ResultsA total of 135 patients with iron-deficiency anemia and 133 controls were enrolled. Celiac disease prevalence was higher in the iron-deficiency anemia group [11.11 vs. 1.51%, OR: 8.18 (1.83-36.55), P=.001). Of the celiac disease patients in the iron-deficiency anemia group, 73.3% had at least one endoscopic sign suggesting villous atrophy, whereas 100% of the celiac disease patients in the control group presented with at least one endoscopic sign. ConclusionsPatients with iron-deficiency anemia have an increased risk for celiac disease. Up to 25% of these patients may not present any endoscopic sign suggesting villous atrophy.

Abnormalities in CD57 + cytotoxic T cells and Vδ1 + γδT cells in subclinical celiac disease in childhood are affected by cytomegalovirus. The Generation R Study

Celiac disease (CD) is a digestive and autoimmune disorder driven by an immune response to modified gluten peptides. Affected intestines show infiltrates of various T-cell and NK-cell subsets. It is currently unclear if individuals with subclinical CD have systemic abnormalities in immune cells. We here studied whether subclinical CD is associated with changes in blood CD57-expressing and Vδ1-expressing lymphocytes in children, and whether cytomegalovirus (CMV) infection modifies this association. Included were 1068 children from the Generation R Study. Serum Immunoglobulin G (IgG) levels against CMV were measured by ELISA; Tissue transglutaminase type 2 antibody (TG2A) levels with fluorescence enzyme immunoassay (FEIA). Duodenal biopsies, additional Human Leukocyte Antigen (HLA) DQ 2.2, 2.5 and 8 and endomysial antibody (EMA) typing were performed in TG2A positive children. Subclinical CD cases (n=12) had 1.8 fold (95% CI 1.06; 3.1) fewer Vδ1+ T cells which was predominantly observed in CMV seronegative children (p-interaction 0.02), and 2.7 fold (95% CI 1.25; 5.99) more CD57+ T cells than HLA DQ2/-DQ8 positive controls (n=339). Hence, children with subclinical CD have alterations in specific blood T cell subsets that are linked to viral pathology. The observed interaction effect between subclinical CD and CMV may contribute to the understanding of disease pathogenesis.

Elevated tissue transglutaminase antibodies in juvenile idiopathic arthritis children: Relation to neutrophil-to-lymphocyte ratio and disease activity

Background: Subclinical gut inflammation is described in juvenile idiopathic arthritis (JIA), so has joint involvement been related to celiac disease (CD). The well-known involvement of tissue transglutaminase (tTG) in the pathogenesis of CD stimulated progress in the field of autoimmune diseases. Aim of the work: To screen JIA children for tTG antibodies and to detect its relation to the neutrophil-lymphocyte ratio (NLR) and disease activity. Patients and methods: The study included 44 JIA children with 44 matched controls. All subjects had no GIT symptoms suggestive of CD. Disease activity was assessed using the juvenile arthritis disease activity score in 27 joints (JADAS-27). The tTG antibodies (IgA and IgG) were assessed. Results: The patients mean age was 12.5±2.8years and disease duration 5.01±2.9years; Female:Male 3.4:1. The mean JADAS-27 score was 12.6±2.04. tTG antibodies were positive in 43.2% of the patients compared to 18.2% control (p=0.01). Antibodies positivity was comparable according to gender and subtypes. The NLR in JIA children (1.62±0.58) was significantly higher than in control (1.3±0.5) (p=0.006). Those with positive tTG antibodies had a significantly reduced body mass index (p=0.02) and increased NLR (p=0.02) compared to those with negative tTG. Only NLR and JADAS-27 would significantly predict antibodies positivity (p=0.037 and p=0.04, respectively). Conclusion: Increased tTG antibodies are frequent in JIA children raising the possibility of an associated subclinical CD. Markedly reduced BMI and increased NLR could forecast the presence of these antibodies. In addition to the JADAS-27, the NLR is a simple test that could predict this association and could be a useful biomarker.

Changes in Presentation of Celiac Disease in Ireland From the 1960s to 2015.

Celiac disease is an immune-mediated enteropathy characterized with high heterogeneity in presentation among genetically predisposed individuals. In recent years, a change in the phenotypic presentation of celiac disease has been reported. We studied clinical presentation, from 1960 through 2015, in Ireland, which has a high incidence of celiac disease. We performed a retrospective analysis of medical charts from patients diagnosed with celiac disease at 5 secondary referral centers in Ireland from 1960 through 2015 (n= 749; median age, 56 years; age range, 18-91 years). The cohort was divided into 5 groups based on year of diagnosis (≤1985, 1986-1995, 1996-2005, 2006-2010, or 2011 and later). We collected findings from clinical presentation at diagnosis; serology tests; small intestinal biopsy analyses; and patients' demographic, clinical, and family data. Presentations at diagnosis were classified according to the Oslo criteria as follows: classical (patients presenting with malabsorption), nonclassical (no signs or symptoms of malabsorption at presentation), or subclinical (below the threshold of clinical detection). The primary outcome was change in clinical presentation of celiac disease over time. Of the 749 patients studied, 512 were female and 237 were male (ratio of 2.2:1). Female patients were diagnosed at younger ages than male patients (42 vs 47 years, respectively; P= .004), and had more immune-mediated conditions than male patients (35.7% for female patients vs 21.5% for male patients; P < .001). For patients diagnosed as adults (after the age of 18 years), the median age of diagnosis increased from 34.0 years during the period ≤1985 to median ages of 44-46 years after 1985 (P < .002). A smaller proportion of patients presented with classical features of celiac disease after 2010 (48.4%) than ≤1985 (85.2%); the proportion of patients with nonclassical or subclinical celiac disease increased from 14.8% ≤1985 to 51.6% after 2010 (P= .006 for each). Biopsies categorized as Marsh 3c decreased, from 52.2% in the period 1996-2005 to 22.5% in the period after 2010 (P= .003). The prevalence of associated thyroid disease has decreased during the study period, from 36.6% ≤1985 to 17.1% after 2010 (P= .039), whereas body mass index at diagnosis increased from 21.5 kg/m2 ≤1985 to 24.8 kg/m2 after 2010 (P < .001). We found the clinical presentation of celiac disease changed significantly in Ireland from 1960 through 2015. The age of presentation in adulthood increased over this time period, as did the proportions of patients with nonclassical or subclinical disease.

Endocrine manifestations in celiac disease.

Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison’s disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet.

Subclinical Celiac Disease Presented with Postpartum Low Back Pain Case Report

Subclinical Celiac Disease Presented with Postpartum Low Back Pain Case Report

Diagnostic screening for subclinical celiac disease using a rapid test in children aged 2-4.

Our aim is to study the prevalence of subclinical celiac disease (CD) and analyze the diagnostic yield of a new rapid test in children aged 2-4. We carried out a cross-sectional study in a sample population of children aged 2-4 from the same metropolitan area. We recruited apparently healthy subjects, and collected clinical, anthropometric, analytical, and serological variables. We also tested for anti-gliadin IgA and anti-transglutaminase IgG and IgA using a rapid immunochromatographic test CD1WB and CD2WB (Operon, Zaragoza, Spain). One hundred and ninety-eight children were recruited, signed the informed consent form, and completed the protocol (mean age 32.3 ± 9.2 mo, 53% males). CD prevalence according to the serological tests was 3% (CI 95%, 1.4-6.4%). Biopsies were used to confirm the diagnosis in all suspected cases. The sensitivity and negative predictive value of the CD2WB immunochromatographic test strip were 100% and 1, respectively. The sensitivity of CD1WB was 16.6% and its specificity was high (89.1%). The prevalence of subclinical CD in the sample group of 2-4-y old was higher than that found by other authors. The CD2WB immunochromatographic test strip is an excellent diagnostic screening tool with high sensitivity and negative predictive value.

Significant bone microarchitecture impairment in premenopausal women with active celiac disease

Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones—distal radius and tibia—in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29years, range: 18–49) and 22 healthy women of similar age (median age 30years, range 21–41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm3 (mean±SD: 274.7±51.7 vs. 324.7±45.8, p 0.0006 at the radius; 264.4±48.7 vs. 307±40.7, p 0.002 at the tibia), trabecular density mg/cm3 (118.6±31.5 vs. 161.9±33.6, p<0.0001 at the radius; 127.9±28.7 vs. 157.6±15.6, p<0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9±2.6 vs. 13.5±2.8, p<0.0001 at the radius; 10.6±2.4 vs. 13.1±1.3, p<0.0001 at the tibia); number of trabeculae 1/mm (1.69±0.27 vs. 1.89±0.26, p 0.009 at the radius; 1.53±0.32 vs. 1.80±0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058±0.010 vs. 0.071±0.008, p<0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm3 860±57.2 vs. 893.9±43, p 0.02; 902.7±48.7 vs. 932.6±32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a—8% decay with p 0.11 in both bones). Patients with symptomatic CD (n=22) had a greater bone microarchitectural deficit than those with subclinical CD. HR-pQCT was used to successfully identify significant deterioration in the microarchitecture of trabecular and cortical compartments of peripheral bones. Impairment was characterized by lower trabecular number and thickness—which increased trabecular network heterogeneity—and lower cortical density and thickness. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture recovers and to what extend after gluten-free diet.

Dermatitis Herpetiformis: Pathognomonic Transglutaminase IgA Deposits in the Skin and Excellent Prognosis on a Gluten-free Diet

Dermatitis herpetiformis (DH) is an itchy, blistering skin disease with sites of predilection at the elbows, knees and buttocks. Although DH is mostly asymptomatic, all patients exhibit small bowel villous atrophy or at least coeliac-type inflammatory changes. Deposition of immunoglobulin A (IgA) in the papillary dermis is a key diagnostic feature of DH. Epidermal transglutaminase (TG3) is the antigen for IgA deposited in the skin, and tissue transglutaminase (TG2) is the antigen for IgA deposited in the small bowel mucosa. Clinically silent, but immunologically active coeliac disease in the gut appears to result in IgA TG3 antibody complexes aggregated into DH skin. The prevalence of DH in northern Europe is high (30-75/100,000), but its incidence is decreasing, possibly due to increased recognition of subclinical coeliac disease. The rash and small bowel heal on a gluten-free diet, which is a life-long treatment. The risk of non-Hodgkin's lymphoma is increased, but in patients with DH who adhere strictly to a gluten-free diet long-term prognosis is excellent.

O-172 Infant Feeding And Anti-tissue Transglutaminase Antibody Levels In Children With Subclinical Celiac Disease: The Generation R Study

Objective To examine whether the timing of gluten introduction and breastfeeding duration are associated with subclinical celiac disease in children at the age of 6 years. Methods This study was embedded in the Generation R study, a population-based prospective cohort study. Participants included 1679 Dutch children positive for HLA-DQ2/DQ8. Data on the timing of gluten introduction ( 7 U/ml) levels. Positive anti-tTG levels were further categorised based on the ≥10 times upper limit of normal (ULN) levels of the test kit (>7–70 U/ml and ≥70 U/ml). Multivariable logistic regression analyses were performed. Results Positive anti-tTG levels were found in 43 children of which 26 children had levels above the 10 times ULN (≥70 IU/ml). The introduction of gluten from the age of 6 months onwards and breastfeeding for 6 months or longer were not significantly associated with positive anti-tTGlevels. In addition, the timing of gluten introduction and duration of breastfeeding were not significantly associated with positive anti-tTG levelsbelow and above the 10 times ULN. Conclusions Delayed introduction of gluten beyond the age of 6 months does not increase the risk of subclinical CD. Also, breastfeeding for 6 months or longer does not decrease the risk of subclinical CD in children at 6 years of age.

Growth Trajectories and Bone Mineral Density in Anti-Tissue Transglutaminase Antibody–positive Children: The Generation R Study

Increased levels of anti-tissue transglutaminase (tTG) have been associated with reduced weight and bone mineral density (BMD) in symptomatic patients with celiac disease. Little is known about the effects of these antibodies in patients with subclinical or other forms of celiac disease. We examined associations between anti-tTG positivity and growth and BMD. In a population-based prospective cohort study, serum samples were collected from children (median age, 6 years; n = 4442) and analyzed for anti-tTG. All children were born between April 2002 and January 2006 and were not previously diagnosed with celiac disease. Children were categorized as anti-tTG negative (<7 U/mL, n = 4249) or anti-tTG positive (≥7 U/mL, n = 57). Children's levels of anti-tTG were further categorized on the basis of ≥10 times upper limit of normal (70 U/mL). Height, weight, and body mass index (BMI) age- and sex-adjusted standard deviation scores (SDS) ([observed value - mean]/SD) were obtained by using Dutch reference growth charts. BMD was measured by dual-energy x-ray absorptiometry. Multivariable linear regression and linear mixed models were performed. Children who tested positive for anti-tTG had reduced growth in weight SDS/year (reduction of 0.05; 95% CI, reductions of 0.09-0.01) and BMI SDS/year (reduction of 0.10; 95% CI, reductions of 0.18-0.01) from 6 months until 6 years, compared with children without anti-tTG; they also tended to have reduced growth in height from 6 months until 6 years (reduction of 0.02 SDS/year; 95% CI, reductions of 0.06-0.02). Children who tested positive for anti-tTG were shorter (0.29 SDS shorter; 95% CI, reductions of 0.55-0.04 SDS), weighed less (0.38 SDS less; 95% CI, reductions of 0.64-0.12), and had lower BMIs (0.26 SDS less; 95% CI, reductions of 0.49-0.03) and BMDs (0.26 SDS less; 95% CI, reductions of 0.45-0.08) at 6 years of age than anti-tTG negative children. Anti-tTG positive children without gastrointestinal symptoms have lower BMDs and reduced growth trajectories until they are 6 years old. This suggests that subclinical or potential celiac disease can affect BMD and growth.

Celiac symptoms in patients with fibromyalgia: a cross-sectional study.

Fibromyalgia is a chronic pain syndrome associated with numerous somatic symptoms including gastrointestinal manifestations of nonspecific nature. Celiac disease and nongluten sensitivity frequently evolve in adults with gastrointestinal and extraintestinal symptoms similar to those found among patients with fibromyalgia. The objective of the present study was to evaluate the presence of celiac-type symptoms among patients with fibromyalgia in comparison with healthy subjects and with those experienced by adult celiac patients and subjects with gluten sensitivity. A list of typical celiac-type symptoms was developed, comparing the frequency of presentation of these symptoms between patients with fibromyalgia (N = 178) and healthy subjects (N = 131), in addition to those of celiac patients and gluten-sensitive patients reported in the literature. The frequency of presentation of every celiac-type symptom, excepting anemia, was significantly higher among patients with fibromyalgia compared to controls (p < 0.0001). Regarding the existing data in the literature, the prevalence of fatigue, depression, cognitive symptoms and cutaneous lesions predominated among patients with fibromyalgia, whereas the prevalence of gastrointestinal symptoms was higher among patients with fibromyalgia compared to gluten-sensitive patients and was similar among patients with fibromyalgia and celiac disease patient. The symptomatological similarity of both pathologies, especially gastrointestinal symptoms, suggests that at least a subgroup of patients with fibromyalgia could experience subclinical celiac disease or nonceliac gluten intolerance.