Consecutive Celiac Disease Patients Research Articles

Autoimmune Polyendocrine Syndromes in Adult Italian Celiac Disease Patients.

Celiac disease (CD) is frequently associated with other autoimmune disorders. Different studies have explored the association between CD and single autoimmune endocrine disease (AED), especially autoimmune thyroiditis (AIT) and type-1 diabetes mellitus (T1DM). Data about CD as a component of autoimmune polyendocrine syndrome (APS) are scant. We analyzed a large dataset including prospectively collected data from 920 consecutive adult CD patients diagnosed in a third-level Italian institution in the 2013-2023 period, The prevalence of isolated autoimmune endocrine diseases and APS were collected. A total of 262 (28.5%) CD patients had at least one associated AED, with AIT (n = 223, 24.2%) and T1DM (n = 27, 2.9%) being the most frequent conditions. In most cases (n = 173, 66%), AEDs were diagnosed after CD. Thirteen patients (1.4%) had at least two of the requested three endocrinopathies, satisfying the diagnosis of type 2 APS. APS-2 is a rare but not exceptional occurrence among Italian CD patients, underscoring the intricate and multifaceted nature of autoimmune disorders. Periodic evaluations of thyroid function and glycaemia should be recommended after the diagnosis of CD together with testing for autoantibodies that may be helpful in assessing disease risk before disease onset. Likewise, implementation of a systematic screening for CD amongst T1DM and other autoimmune endocrine diseases are paramount.

Comparison of Clinical, Biochemical and Histological Features between Adult Celiac Patients with High and Low Anti-Transglutaminase IgA Titer at Diagnosis and Follow-Up

In adults, celiac disease (CD) diagnosis is based on specific serology (anti-transglutaminase IgA-anti-tTG) and duodenal histology. Evidence is raising the possibility of perform CD diagnosis based only on high anti-tTG titer in children. We aimed to evaluate clinical, histological and biochemical differences between adult patients with high tTG IgA titer (HT) and those with low titer (LT) at CD diagnosis and follow-up. This retrospective study included consecutive adult CD patients divided into two groups: HT (anti-tTG > 10 × ULN) and LT (anti-tTG < 10 × ULN). Clinical, biochemical and histological features were compared between groups at CD diagnosis and at follow-up. A total of 291 patients were included (HT: 47.1%; LT: 52.9%). At CD diagnosis, HT patients showed a non ‘classical’ presentation (p = 0.04), Marsh 3C (p = 0.005), hypoferritinaemia (p = 0.006) and osteopenia/osteoporosis (p = 0.04) more frequently than LT patients. A total of 216 patients (HT: 48.6%; LT: 51.4%) performed a follow-up after a median Gluten-free diet of 14 months; HT patients had persistent antibodies positivity (p = 0.001) more frequently and GI symptoms (p = 0.04) less frequently than LT patients. In conclusion, HT patients presented severe histological damage more frequently at diagnosis, recovering similarly to LT patients after the start of the Gluten-free diet. At follow-up, anti-tTG persisted positive in HT more frequently compared to LT patients, without differences regarding histological recovery and clinical improvement.

Hepatic Steatosis in Patients with Celiac Disease: The Role of Packaged Gluten-Free Foods.

Background: An increased risk of nonalcoholic fatty liver disease (NAFLD) in patients with celiac disease (CD) adhering to a gluten-free diet (GFD) was recently reported. The nutritional composition of packaged gluten-free foods (PGFF) has been proposed as a possible cause. This hypothesis has not been investigated further, since a systematic structural nutritional interview for all patients would be problematic in clinical practice. Methods: We administered a simple questionnaire based on a Recency, Frequency, and Monetary value (RFM) analysis (a cornerstone of direct marketing segmentation) to consecutive CD patients on a GFD for >6 months and verified its association with NAFLD. Subgroup analyses were performed to understand whether specific patterns of PGFF consumption were significantly associated with NAFLD. Results: Amongst 147 patients (female 82%, median age 42 years), 45 (30.6%) had NAFLD. Total RFM score (adjusted odds ratio = 1.223, 95% CI: 1.059–1.413, p = 0.006), body mass index, and total cholesterol and triglycerides were independently related to NAFLD, and “Bread and bakery” (p = 0.002), “salty convenience” (p = 0.005), and “sweet convenience” (p = 0.049) products were significantly related with NAFLD. Also, questions about the number of purchased PGFF in the last month (monetary value) and different categories of PGFF consumed in the last week (recency) were particularly able to identify NAFLD patients. Conclusions: The specific GFD dietary habits of CD patients were correlated with the degree of risk of NAFLD. Information was obtained through a questionnaire which could be used in clinical practice to favor a patient-tailored approach and in future studies to verify the reproducibility of our results in different geographical areas.

Association in Clinical Practice Between Gluten Intake and Gluten Immunogenic Peptides in Celiac Children.

The dietary compliance and its assessment in celiac disease (CD) patients on a strict gluten-free diet (GFD) remain a challenge. Two relatively new, validated methods have been proposed to detect occasional gluten ingestion: standardized dietary questionnaire and determination of urinary gluten immunogenic peptides (GIPs). Our aim was to prospectively assess dietary compliance via these methods and compare their results with those of tissue transglutaminase antibodies (tTGA). This was a prospective single-center study. Consecutive CD patients (aged 1-18 years) on a GFD scheduled for regular consultation between March and August 2019 were invited. In addition to standard care, a completed dietary questionnaire and urine sample for GIP were collected. Pearson's chi-square test, Fisher's exact test, and Mann-Whitney U test were performed. Of the 156 eligible children, 110 provided informed consent. Completed dietary questionnaire, GIP, and tTGA results were available from 86 children (median age 12.8 years, median GFD duration 30 months, 65% female). Adherence to the GFD evaluated by GIP, dietary questionnaire, and anti-tTGA was 94.2%, 75.6% and 94.2%, respectively. No association was found between the tTGA results and the detection of GIP, as well as between the tTGA results and the dietary questionnaires scores (P= .5 and .312, respectively). The participants perceived both the questionnaire and the measurement of GIP as reassuring with regard to correct implementation of the GFD. All the 3 methods have limitations to monitor dietary compliance. The comparison of their performance shows that the best single method is the use of the validated dietary questionnaire, which should therefore be implemented in the regular care for children with CD. The most effective combination of dietary questionnaire and urinary GIP determination should be used in specific clinical situations.

Clinical Value of Tissue Transglutaminase Antibodies in Celiac Patients over a Long Term Follow-Up.

Introduction & Aim: Anti-tissue transglutaminase antibody (tTGA) titer is used during the follow-up of celiac patients to evaluate gluten-free diet (GFD) responsiveness. However, no clear data are available on this issue. The aim of this study was to evaluate tTGA significance during celiac disease (CD) monitoring. Methods: From January 2017 to January 2020, consecutive CD patients on a GFD with persistent positive tTGA were enrolled. Antibody titres were evaluated on a yearly basis from CD diagnosis to the last follow-up. Urinary gluten detection tests, duodenal histology and capsule enteroscopy (CE) were performed. A tTGA-positive cohort was compared with a control group composed of 212 treated CD patients with negative tTGA. Results: 65 patients (12% males, median age at enrollment and CD diagnosis, 37 (14–86) and 31 (1–76), respectively, median follow up 4 (1–26) years) presented with positive tTGA during follow-up. Overall, the tTGA titres were 3 (1–79) fold increased (ULN). Three different tTGA trends were recognized: (I) 36 (55%) patients with a progressive titres decrease; (II) 16 (25%) patients with a fluctuating behavior; (III) 13 (20%) patients with a steady state or increased titres. tTGA+ patients did not present with different clinical and demographic parameters. Duodenal atrophy was present in 10% vs. 36% of the tTGA positive vs. negative group (p < 0.005), respectively. Gluten detection results were positive in 3 (8%) cases, all in the III group. In tTGA+ patients, CE did not identify any CD-related complications. Conclusions: tTGA positivity during CD follow up did not present a relevant clinical significance without association with autoimmune comorbidities and mucosal damage.

Beneficial Effects of a Low-Nickel Diet on Relapsing IBS-Like and Extraintestinal Symptoms of Celiac Patients during a Proper Gluten-Free Diet: Nickel Allergic Contact Mucositis in Suspected Non-Responsive Celiac Disease.

Background and Aim: Nickel (Ni)-rich foods can induce allergic contact mucositis (ACM) with irritable bowel syndrome (IBS)-like symptoms in predisposed subjects. Ni ACM has a high prevalence (>30%) in the general population and can be diagnosed by a Ni oral mucosa patch test (omPT). Many celiac disease (CD) patients on a gluten-free diet (GFD) often show a recrudescence of gastrointestinal and extraintestinal symptoms, although serological and histological remission has been achieved. Since a GFD often results in higher loads of ingested alimentary Ni (e.g., corn), we hypothesized that it would lead to a consequent intestinal sensitization to Ni in predisposed subjects. We wanted to (1) study Ni ACM prevalence in still symptomatic CD patients on a GFD and (2) study the effects of a low-Ni diet (LNiD) on their recurrent symptoms. Material and Methods: We recruited 102 consecutive CD patients (74 female, 28 male; age range 18–65 years, mean age 42.3 ± 7.4) on a GFD since at least 12 months, in current serological and histological remission (Marsh–Oberhuber type 0–I) who complained of relapsing gastrointestinal and/or extraintestinal symptoms. Inclusion criteria: presence of at least three gastrointestinal symptoms with a score ≥5 on the modified Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. Exclusion criteria: IgE-mediated food allergy; history of past or current cancer; inflammatory bowel diseases; infectious diseases including Helicobacter pylori; lactose intolerance. All patients enrolled underwent Ni omPT and followed a LNiD for 3 months. A 24 symptoms questionnaire (GSRS modified according to the Salerno Experts’ Criteria, with 15 gastrointestinal and 9 extraintestinal symptoms) was administered at T0 (free diet), T1 (GFD, CD remission), T2 (recurrence of symptoms despite GFD), and T3 (GFD + LNiD) for comparisons. Comparisons were performed using Wilcoxon signed-rank test. RESULTS: Twenty patients (all female, age range 23–65 years, mean age 39.1 ± 2.9) out of 102 (19.6%) were finally included. All 20 patients enrolled (100%) showed positive Ni omPT, confirming an Ni ACM diagnosis. A correct GFD (T0 vs. T1) induced the improvement of 19 out of the total 24 (79.2%) symptoms, and 14 out of 24 (58.3%) were statistically significant (p-value < 0.0083 according to Bonferroni correction). Prolonged GFD (T1 vs. T2) revealed the worsening of 20 out of the total 24 (83.3%) symptoms, and 10 out of 24 (41.7%) were statistically significant. LNiD (T2 vs. T3) determined an improvement of 20 out of the total 24 (83.4%) symptoms, and in 10 out of 24 (41.7%) symptoms the improvement was statistically significant. Conclusions: Our data suggest that the recrudescence of gastrointestinal and extraintestinal symptoms observed in CD subjects during GFD may be due to the increase in alimentary Ni intake, once gluten contamination and persisting villous atrophy are excluded. Ni overload can induce Ni ACM, which can be diagnosed by a specific Ni omPT. Improvement of symptoms occurs after a proper LNiD. These encouraging data should be confirmed with larger studies.

A23 NUTRITIONAL DEFICIENCIES ARE FREQUENT IN CELIAC PATIENTS ON A GLUTEN-FREE DIET, REGARDLESS OF THE DURATION AND COMPLIANCE OF THE DIET

Abstract Background The only available treatment for celiac disease (CD) is adherence to a strict gluten-free diet (GFD). CD is associated with several nutritional deficiencies, which could be explained by malabsorption when the disease is active. However, the magnitude of nutritional deficiencies in treated CD and how this is influenced by the duration and compliance of GFD is less clear. Aims We aim to evaluate the presence of nutritional deficiencies in celiac patients on short term (≤2yrs) vs long-term (&amp;gt;2yrs) GFD, and in those with persistent symptoms or asymptomatic in the follow up. Methods We included consecutive biopsy-proven CD patients attending the McMaster Adult Celiac Clinic. GFD adherence was assessed by validated Celiac Dietary Adherence Test (CDAT) and by anti-tissue transglutaminase antibody IgA(tTG IgA) levels. Serology, vitamins and minerals were measured in blood samples collected at enrolment. Continuous data was expressed as Median (IQR) and categorical data as proportion%. Mann-U-Whitney and Chi2 were used to compare difference between groups. Results We enrolled 171 CD patients (80% female; Median age 43 years). 76/171 (44%) of CD patients were following a GFD for over 2 years. Eighty-two percent of the patients (141/171) had persistent symptoms in the follow up and 80.7% had normal tTG IgA levels. The most common nutritional abnormalities were deficiencies in zinc (56%), iron (23%), copper (20%). Chromium was increased in 74% of patients. There were no differences in nutritional deficiencies between group of patients with short and long-term duration of GFD, nor between those strictly compliant with GFD compared to those fairly compliant (p&amp;gt;0.05). Conclusions Nutritional deficiencies are frequent in celiac patients on a GFD regardless of the presence of symptoms, dietary compliance or duration. The previous suggest that nutrients deficiencies may be more related to GFD nutritional inadequacy rather than malabsorption. Funding Agencies None

The role of TMPRSS6 and HFE variants in iron deficiency anemia in celiac disease.

We investigated the role of HFE C282Y, H63D, and TMPRSS6 A736V variants in the pathogenesis of iron deficiency anemia (IDA) in celiac disease (CD) patients, at diagnosis and after 1year of gluten-free diet (GFD). Demographic and clinical features were prospectively recorded for all CD patients between 2013 and 2017. C282Y, H63D, and A736V variants were evaluated for CD patients and controls. Finally, 505 consecutive CD patients and 539 age-matched control subjects were enrolled. At diagnosis, 229 CD subjects had IDA (45.3%), with a subgroup of anemic patients (45.4%) presented persistent IDA at follow-up. C282Y allele frequency was significantly increased in CD compared with controls (1.1% vs 0.2%, P = .001), whereas H63D and A736V allele frequencies were similar among patients and controls (P = .92 and .84, respectively). At diagnosis, C282Y variant in anemic CD patients was significantly increased compared to nonanemic group (2% and 0.5%, P = .04). At follow-up, A736V was significantly increased in IDA persistent than in IDA not persistent (57.7% vs 35.2%, P < .0001). CD patients with H63D mutation showed higher Hb, MCV, serum iron, and ferritin levels than subjects without HFE mutations. Decreased hepcidin values were observed in anemic compared to nonanemic subjects at follow-up (1.22 ± 1.14 vs 2.08 ± 2.15, P < .001). This study suggests a protective role of HFE in IDA CD patients and confirms the role of TMPRSS6 in predicting oral iron response modulating hepcidin action on iron absorption. Iron supplementation therapeutic management in CD could depend on TMPRSS6 genotype that could predict persistent IDA despite iron supplementation and GFD.

Normal Bone Mineral Density Associates with Duodenal Mucosa Healing in Adult Patients with Celiac Disease on a Gluten-Free Diet.

Impairment of bone mineral density (BMD) is frequent in celiac disease (CD) patients on a gluten-free diet (GFD). The normalization of intestinal mucosa is still difficult to predict. We aim to investigate the relationship between BMD and duodenal mucosa healing (DMH) in CD patients on a GFD. Sixty-four consecutive CD patients on a GFD were recruited. After a median period of a 6-year GFD (range 2–33 years), patients underwent repeat duodenal biopsy and dual-energy X-ray absorptiometry (DXA) scan. Twenty-four patients (38%) displayed normal and 40 (62%) low BMD, 47 (73%) DMH, and 17 (27%) duodenal mucosa lesions. All patients but one with normal BMD (23 of 24, 96%) showed DMH, while, among those with low BMD, 24 (60%) did and 16 (40%) did not. At multivariate analysis, being older (odds ratio (OR) 1.1, 95% confidence interval (CI) 1.03–1.18) and having diagnosis at an older age (OR 1.09, 95% CI 1.03–1.16) were associated with low BMD; in turn, having normal BMD was the only variable independently associated with DMH (OR 17.5, 95% CI 1.6–192). In older CD patients and with late onset disease, BMD recovery is not guaranteed, despite a GFD. A normal DXA scan identified CD patients with DMH; thus, it is a potential tool in planning endoscopic resampling.

Inadequate seroconversion rates in celiac disease after 3 doses of hepatitis B vaccine, administered at 3, 5 and 11 months of life

Celiac disease (CD) is a clinical condition potentially impairing the immune system. We tested the hypothesis that CD could hinder seroconversion following hepatitis B vaccine (HBV). We compared 81 consecutive CD patients (24 male and 57 female) with a median [interquartile range (IQR)] age of 10 (7) yr (range 2–30 yr) and 50 controls (26 male and 24 female) with a median (IQR) age 7 (7) yr (range 1–26 yr) who received a standard immunisation schedule with HBV given at 3, 5 and 11 mo of. The median (IQR) interval from the last dose of HBV was higher in CD patients as compared to controls [10 (7), range 2–29 yr vs. 6 (7), range 1–26 yr; P

Do patients with celiac disease patients differ from those with concurrent celiac disease with type 1 diabetes mellitus?

Background and objectives Celiac disease (CD) and type 1 diabetes mellitus (T1DM) share common genetic loci. Patients with T1DM developing CD may remain asymptomatic and some of the common symptoms of CD may be considered as part of the chronic complications of diabetes like gastrointestinal intolerance, diarrhea, nocturnal diarrhea, alternate diarrhea and constipation. There are no reports on comparison of presenting features of patients with CD and those with CD and T1DM together. The present study was planned to compare clinical, biochemical and hormonal profile of patients of CD and CD with T1DM. Patients and methods Consecutive CD patients with and without T1DM ≤ 20 years seen by us were evaluated clinically and underwent thyroid, gonadal function tests (where applicable) and serum cortisol, besides routine hemogram and biochemical tests. Patients were subjected to screening for CD by anti tissue transglutaminase antibodies (tTGAb) and those positive were subjected to endoscopy of descending part of the duodenum, and 3 biopsies were taken. Histological interpretation was done by an experienced pathologist and recorded as per modified Marsh classification [1]. Patients were diagnosed to have CD as per modified ESPGHAN criteria [2] and T1DM as per ADA position statement [3]. All patients received gluten free diet (GFD) and / or diabetic diet. Patients with CD alone (group A) were compared with those having CD with T1DM (Group B). Results 109 patients (57 males) with mean age of 14.9±2.9 year fulfilled the eligibility criteria. 23 (21.1%) had T1DM

Are positive serum-IgA-tissue-transglutaminase antibodies enough to diagnose coeliac disease without a small bowel biopsy? Post-test probability of coeliac disease

BackgroundIt has been suggested that high titres of tTG are associated with elevated positive predictive values (PPV) for celiac disease. However, the PPV of a strongly positive tTG will depend on the celiac disease prevalence in the different risk groups of the disease AimsTo assess the PPV of a strongly positive tTG for celiac disease. In addition, to calculate the post-test probability for celiac disease of a strongly positive tTG in a setting of routine clinical practice. Methods145 consecutive celiac disease patients with positive tTG, and with a small bowel biopsy were included. The PPV for different cut-off points of tTG levels for the diagnosis of celiac disease was assessed. In addition, the cut-offs associated with higher PPV were used to calculate the positive likelihood ratio. A simulation in a setting of routine clinical practice was performed to calculate the post-test probability of celiac disease. ResultsNo cut-off level was associated with a PPV of 100%. A cut-off of 80U/mL (11.4×upper normal limit) was associated with the higher PPV value of 98.6%. In the most frequent clinical situations, which in general have a pre-test probability <10%, the post-test probability after having a strongly positive tTG was 90% or less. ConclusionsA strongly positive tTG should not be enough to diagnose celiac disease in the most frequent clinical situations, small bowel biopsy remaining as the gold standard in these cases.

1452 Seroconversion Rates in Celiac Disease After Hbv Vaccination

Celiac disease (CD) is a condition potentially impairing seroconversion against hepatitis B virus (HBV). Methods. We studied retrospectively 81 consecutive CD patients (24 M and 57 F) with a median (interquartile range, IQR) age of 10 (7) yr (range 2-30 yr) and 50 controls (26 M and 24 F) with a median (IQR) age 7 (7) yr (range 1-26 yr) who received a standard anti-HBV vaccination schedule at 3, 5 and 11 months of age. Subjects affected by autoimmune and neoplastic diseases or immunosuppressive treatment where excluded from the study. Results: The median (IQR) interval from the last dose of vaccine was higher in CD patients as compared to controls [10 (7), range 2-29 yr vs. 6 (7), range 1-26 yr, p < 0.0001]. The median (IQR) age of gluten introduction was comparable in the two groups [6 (1), range 4-12 mo vs. 6 (1), range 5-11 mo]. The median (IQR) duration of gluten intake in the CD group was 3.5 (4.8) yr (range 0.2- 12.3 yr). A cut-point ≥ 10 mUI/ml for HbsAg title was considered to indicate seroconversion for HBV vaccination. 33/81 CD patients did not seroconverte compared to 10/50 controls (p < 0.05). The Odds ratio of a protective HbsAg title in CD subjects vs controls was 0.36 (95% CI, 0.16-0.83, p < 0.0001) and was not associated with gender, the interval from the last administration of the vaccine nor with the duration of gluten intake in CD patients.

Anti-microbial antibodies in celiac disease: Trick or treat?

To determine the prevalence of a new set of anti-glycan and anti-outer membrane protein (anti-OMP) antibodies in a Hungarian cohort of adult Celiac disease (CD) patients. 190 consecutive CD patients [M/F: 71/119, age:39.9 (SD:14.1) years], 100 healthy, and 48 gastrointestinal controls were tested for glycan anti-Saccharomyces cerevisiae (gASCA), anti-laminaribioside (ALCA), anti-chitobioside, anti-mannobioside, anti-OMP antibodies and major NOD2/CARD15 mutations. Thirty out of 82 CD patients enrolled at the time of diagnosis were re-evaluated for the same antibodies after longstanding gluten-free diet (GFD). 65.9% of the CD patients were positive for at least one of the tested antibodies at the time of the diagnosis. Except anti-OMP and ALCA, anti-microbial antibodies were exclusively seen in untreated CD; however, the overall sensitivity was low. Any glycan positivity (LR+: 3.13; 95% CI: 2.08-4.73) was associated with an increased likelihood ratio for diagnosing CD. Significant correlation was found between the levels of anti-glycan and anti-endomysial or anti-transglutaminase antibodies. Anti-glycan positivity was lost after longstanding GFD. Anti-glycan antibody titers were associated with symptoms at presentation, but not the presence of NOD2/CARD15 mutations. Patients with severe malabsorption more frequently had multiple antibodies at diagnosis (P = 0.019). The presence of anti-glycan antibodies in CD seems to be secondary to the impaired small bowel mucosa which can lead to increased antigen presentation. Furthermore, anti-glycan positivity may be considered an additional marker of CD and dietary adherence.

Unexplained Elevated Serum Pancreatic Enzymes: A Reason to Suspect Celiac Disease

The frequency of elevated serum pancreatic enzymes in patients with celiac disease (CD) is unknown. The aim of this study was to evaluate the serum levels of pancreatic enzymes in CD patients. Serum pancreatic isoamylase and lipase levels were assayed in 90 adult and 112 pediatric consecutive CD patients at diagnosis and after 12 months of gluten-free diet (GFD). Serum elastase and trypsin levels were assayed in a subgroup of adult CD patients. Pancreatic ultrasonography was also performed. Twenty-six adult (29%) and 29 pediatric (26%) CD patients exhibited elevated values of serum pancreatic amylase and/or lipase; trypsin was elevated in 69% and elastase in 19%. The frequency of elevated serum pancreatic enzymes observed was identical in the patients with "typical" and "atypical" CD symptoms and in the asymptomatic patients. Most of the elevated values were lower than 2-fold the threshold limits. Elevated pancreatic enzymes were not associated with alcohol consumption, drug use, presence of abdominal pain, or diabetes mellitus. Abdominal ultrasound scan showed no abnormal findings in the pancreatic region in any of the CD patients. After 12 months of GFD, pancreatic amylase was elevated in 3 cases and lipase in 2 cases; these patients had not strictly adhered to the GFD. We demonstrated a frequency of about 25% of elevated pancreatic enzymes values in CD patients, including subjects without gastrointestinal manifestations and apparently asymptomatic subjects. The finding of elevated serum amylase or lipase level, in the absence of signs of pancreatic disease, would appear to suggest a need to screen for celiac disease.

IS CELIAC DISEASE SCREENING IN RISK GROUPS JUSTIFIED? A LONG-TERM FOLLOW-UP STUDY

Aim: The benefits of celiac disease (CD) screening are debatable and the compliance to gluten-free diet (GFD) in screen-detected patients is thought to be poor; we investigated the dietary compliance, quality of life (QoL), physical well-being and bone mineral density in screen-detected CD patients after long-term treatment. Methods: 53 consecutive screen-detected CD patients (both children and adults at the diagnosis of CD) were enrolled to follow-up study after median of 14 (range 5-21) years of commencement to GFD; screening was carried out because of family history of CD or associated autoimmune diseases. Dietary compliance was assessed by an interview, a 4-day food record and CD serology. QoL was evaluated by Psychological General Well-Being (PGWB), SF-36 and gastrointestinal symptoms by Gastrointestinal Symptom Rating Scale·questionnaires. The results were compared to those in 44 symptom-detected treated CD patients, non-CD controls and general population. Results: The long-term compliance to GFD did not differ significantly between screen-detected and symptom-detected CD patients, being good in 83% and 77% respectively. QoL was as good in screen-detected treated CD patients as in symptom-detected CD and nonceliac controls when measured by PGWB. Mean value of mental health in SF-36 was significantly better in screen-detected treated CD than in the general population; in other items there was a similar tendency. Screen-detected long-term treated CD patients had slightly less abdominal symptoms and better bone mineral density than symptom-detected treated CD patients (not significant). Summary: Long-term compliance to GFD in screen-detected CD patients was good. Despite evident dietary restrictions, the QoL was comparable to that of symptom-detected patients, and even to non-celiac controls or general population. Conclusions: In terms of QoL and compliance CD screening and early treatment seems to be conceivable in CD risk groups. These data can be applied when decisions about mass-screening of CD in general population are rationalized.

Anti-Actin Antibodies in Celiac Disease: Correlation with Intestinal Mucosa Damage and Comparison of ELISA with the Immunofluorescence Assay

The presence in the sera of celiac disease (CD) patients of anti-actin autoantibodies (AAAs) has been suggested as a marker of severe intestinal villus atrophy (1). AAAs have been detected with an immunofluorescence (IF) technique and seem to contribute to villus cytoskeleton damage and to the pathogenesis of intestinal damage in CD (2). The aims of the present study were to evaluate the relationship between the presence of serum IgA AAAs and severity of intestinal mucosa damage in CD patients and to compare the IF assay with a new ELISA for IgA AAA determination. We enrolled 150 individuals in the study. IgA AAAs were assayed in 58 consecutive CD patients diagnosed between January and December 2003: 30 adults (10 male; median age, 32 years; range, 18–56 years) and 28 children (14 male; median age, 18 months; range, 1–12 years). The sera were collected at CD diagnosis, after overnight fasting, and were frozen at −80 °C for a mean of 9 months before AAA determination. In 20 patients, AAAs were reassayed after 6–12 months of gluten-free diet. CD diagnosis was based on the revised criteria of the European Society of Pediatric Gastroenterology and Nutrition (3). We enrolled 64 patients as “healthy” controls [34 adults evaluated for suspected hypercholesterolemia (15 male; median age, 35 years; range, 18–56) and 30 children with recurrent pharyngotonsilitis (14 male; median age, 3 years; range, 1–12 years)]. None of these controls had symptoms or laboratory signs suggesting CD, and all were negative for anti-endomysium (EmA) and anti-transglutaminase (anti-tTG). We enrolled an additional 28 adults with autoimmune or gastrointestinal diseases other than CD as “disease” controls: type 1 autoimmune hepatitis (AH; 6 cases), type 2 AH (4 cases), systemic lupus erythematosus (4 cases), Sjogren disease (3), primary biliary cirrhosis (2), Crohn disease (4), multiple food intolerance (3), …

Hypertransaminasemia in pediatric celiac disease patients and its prevalence as a diagnostic clue.

The aims of this study were to evaluate the following: 1) the prevalence of hypertransaminasemia (HT) in a pediatric celiac disease (CD) and its relation with clinical parameters; 2) the frequency of HT as the only manifestation of pediatric CD; and 3) the evolution of HT after a gluten free diet. A total of 114 consecutive pediatric CD patients were studied (60% with classical and 40% with atypical forms). Antiendomisyum antibodies and anti-tissue transglutaminase antibodies were determined in patients with a clinical suspicion of CD (including unexplained chronic HT), in patients at risk, and in patients with preoperative increased ALT activity for minor surgery. CD was confirmed by duodenal biopsy. At baseline, the relationship between clinical factors and aminotransferase status was univariately and multivariately assessed. After starting a gluten free diet, patients were followed up, until serological markers cleared and serum aminotransferase normalized. HT occurred in 32% of patients (37 of 114) at diagnosis. HT was the only manifestation of CD in five patients (4.3%). Patients with HT were younger (2.9 +/- 0.4 yr) than patients with normal aminotransferases (5.1 +/- 0.5 yr) (p = 0.007). A higher percentage of patients with classical CD tend to have abnormal aminotransferases (73%; 95% CI = 65-81%) than do patients with atypical CD (27%; 95% CI = 19-35%) (p = 0.068). Logistic regression analysis showed that only younger age was significantly associated with HT (p = 0.039; OR = 0.8; 95% CI = 0.71-0.99). Aminotransferases normalized with a gluten free diet in all 35 patients who were followed-up, either before (n = 18) or at the same time (n = 17) as serological markers cleared. HT is a frequent finding in pediatric CD patients and, in a substantial proportion, may be the only manifestation of CD. Thus, serological markers of CD should be introduced in the first step of the diagnostic workup of liver diseases in pediatric patients.

Hypertransaminasemia in pediatric celiac disease patients and its prevalence as a diagnostic clue

OBJECTIVES: The aims of this study were to evaluate the following: 1) the prevalence of hypertransaminasemia (HT) in a pediatric celiac disease (CD) and its relation with clinical parameters; 2) the frequency of HT as the only manifestation of pediatric CD; and 3) the evolution of HT after a gluten free diet. METHODS: A total of 114 consecutive pediatric CD patients were studied (60% with classical and 40% with atypical forms). Antiendomisyum antibodies and anti-tissue transglutaminase antibodies were determined in patients with a clinical suspicion of CD (including unexplained chronic HT), in patients at risk, and in patients with preoperative increased ALT activity for minor surgery. CD was confirmed by duodenal biopsy. At baseline, the relationship between clinical factors and aminotransferase status was univariately and multivariately assessed. After starting a gluten free diet, patients were followed up, until serological markers cleared and serum aminotransferase normalized. RESULTS: HT occurred in 32% of patients (37 of 114) at diagnosis. HT was the only manifestation of CD in five patients (4.3%). Patients with HT were younger (2.9 ± 0.4 yr) than patients with normal aminotransferases (5.1 ± 0.5 yr) ( p = 0.007). A higher percentage of patients with classical CD tend to have abnormal aminotransferases (73%; 95% CI = 65–81%) than do patients with atypical CD (27%; 95% CI = 19–35%) ( p = 0.068). Logistic regression analysis showed that only younger age was significantly associated with HT ( p = 0.039; OR = 0.8; 95% CI = 0.71–0.99). Aminotransferases normalized with a gluten free diet in all 35 patients who were followed-up, either before (n = 18) or at the same time (n = 17) as serological markers cleared. CONCLUSIONS: HT is a frequent finding in pediatric CD patients and, in a substantial proportion, may be the only manifestation of CD. Thus, serological markers of CD should be introduced in the first step of the diagnostic workup of liver diseases in pediatric patients.

MICA-A5.1 allele is associated with atypical forms of celiac disease in HLA-DQ2-negative patients.

We selected 38 consecutive celiac disease (CD) patients (from a group of 316 consecutive CD patients) and 91 healthy blood donors, all of whom were HLA-DQ2 (DQA1*0501/DQB1*0201) negative, and investigated the presence of the classically associated alleles HLA-DQ8 and HLA-DRB4. We also studied the distribution of MICA transmembrane alleles in the two clinical forms of the disease. For this reason, these 38 DQ2-negative patients were subdivided into two groups: 18 typical CD patients and 20 atypical CD patients. No differences were found in the distribution of the DRB4 allele between DQ2-negative patients and controls. The HLA-DQ8 heterodimer (DQA1*03xx/DQB1*0302) was increased in CD patients (29%) compared with controls (10%), but no statistical differences were found. No differences were observed in the frequency of these alleles between either group of CD DQ2-negative patients. MICA-A5.1 was increased in atypical CD patients when compared with the typical forms of disease ( P(c)=0.03) and with healthy controls (P(c)=0.002). No other MICA allele was found to be significantly increased in the groups under study. The presence of MICA-A5.1 in atypical CD DQ2-negative patients may indicate a possible role of this allele in the development of CD.