Gluten and dyspepsia

Celiac disease: India on the global map

Management of Celiac Disease: Beyond the Gluten-Free Diet

The diagnosis of celiac disease (CD) is based on the histological identification of gluten-sensitive enteropathy and detection of anti-tissue transglutaminase antibodies (tTGA) and/or endomysial antibodies. Serial measurements of tTGA are now recommended as a follow-up strategy to monitor compliance with a gluten-free diet (GFD). We evaluated the performances of a quantitative radiobinding assay (RBA) of tTGA immunoglobulin A at diagnosis and during monitoring of GFD in pediatric CD. Eighty children with confirmed CD were selected. Levels of serum tTGA measured by RBA and a commercial enzyme-linked immunosorbent assay (ELISA) were compared at diagnosis. The relation between RBA-tTGA levels and histological damage was analyzed, as well as the time course of tTGA clearance during GFD. Both RBA and ELISA showed high sensitivity and specificity for tTGA detection at diagnosis. There was no relation between RBA-tTGA levels at diagnosis and severity of mucosal damage. Upon initiation of GFD, the rate of RBA-tTGA positivity declined slower than that of endomysial antibodies positivity, with >50% of the children still tTGA positive at year 5; however, tTGA levels decreased rapidly during the first year of GFD and more slowly thereafter. Children who seroreverted had lower tTGA levels at diagnosis (2080±1554 cpm) than those who remained tTGA positive throughout follow-up (3688±1435 cpm). The high sensitivity of RBA is likely responsible for higher tTGA positivity rates during GFD than previously reported with ELISA. A decreasing trend for tTGA levels may represent a better surrogate marker of compliance with GFD than absolute normal tTGA levels.

A negative fallout of COVID-19 lockdown in Italy: Life-threatening delay in the diagnosis of celiac disease

Background: Studies assessing the association between coeliac disease (CD) and psoriasis show conflicting results. Objective: To assess in the primary care setting the prevalence of CD in patients with psoriasis and the response to a gluten-free diet (GFD) in subjects with psoriasis and CD. Methods: We enrolled 218 patients with psoriasis and 264 controls. Coeliac screening was carried out in all subjects (Eurospital, Trieste, Italy). In subjects with a positive serology, the diagnosis of CD was confirmed histologically. Results: Nine (4.1%) psoriatic patients had positive anti-tissue transglutaminase antibodies compared to only 1 among controls (0.4%, p < 0.05; OR 2.03, 95% CI 1.42-90.11). The diagnosis of CD was confirmed histologically in all 10 subjects. At 6 months GFD was associated with a great improvement of skin lesions in 7 out of 8 patients with psoriasis. Conclusion: Our multicentre primary care study showed an high prevalence of CD in psoriasis and an improvement of skin lesions in CD under GFD.

Gluten-free diet, chromosomal abnormalities, and cancer risk in coeliac disease.

Celiac Disease: Advances in Treatment via Gluten Modification

Type 1 diabetes mellitus (T1DM) may be associated with other autoimmune diseases. Celiac disease (CD), another autoimmune disorder that mainly affects the small intestine, is caused by intolerance to gluten ingestion. CD has a higher prevalence in patients with T1DM than in the general population. However, the prevalence of CD in patients with T1DM in Japan is unknown. This study investigated the prevalence of CD in Japanese patients with T1DM. We included 115 patients with T1DM treated at Hyogo Brain and Heart Center from December 2020 to April 2021. A questionnaire survey about dietary habits and abdominal symptoms was administered, and serum anti-tissue transglutaminase (TTG) antibody titers were determined for all participants. A CD (CD-seropositive) diagnosis was based on TTG levels >10 U/ml. Fifty-eight patients (50.4%) had some abdominal symptoms (such as constipation, diarrhea, and abdominal pain). The average TTG-IgA antibody titer was 0.75 ± 0.49 U/ml and negative (<10 U/ml) in all patients. In conclusion, the prevalence of CD among patients with T1DM at our hospital was 0%. Thus, the prevalence of CD in Japan is low compared to that in other countries, even among patients with T1DM, who are considered to have high comorbidity rates.

Short stature is a common extraintestinal manifestation of celiac disease (CeD). We conducted a systematic review and meta-analysis to assess the global prevalence of CeD in patients presenting with short stature. We searched Medline and EMBASE databases for the keywords "celiac disease, coeliac disease, anti-gliadin, tissue transglutaminase antibody, anti-endomysial antibody, short stature and growth retardation." All the studies published from January 1991 to May 2020 were included. Patients without any prior evaluation for short stature were classified as all-cause short stature, while prior evaluated patients, where no cause was found for short stature, were classified as idiopathic short stature. The diagnosis of CeD was based on the European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines. A random-effects model was used to pool the data. Seventeen studies screening 3759 patients (1582 with all-cause short stature and 2177 with idiopathic short stature) were included. The pooled seroprevalence of CeD based on positive anti-tissue transglutaminase antibody and anti-endomysial antibody was 11.2% (95% CI 4.0-21.2%; I2 =86%) and 9.7% (95% CI 2.7-20.2%; I2 =95%) for all-cause and idiopathic short stature, respectively. Similarly, pooled prevalence of biopsy-confirmed CeD was 7.4% (95% CI 4.7-10.6%; I2 =76%) and 11.6% (95% CI 4.1-22.2%; I2 =97%), for all-cause and idiopathic short stature, respectively. There was an overall severe risk of selection bias and significant heterogeneity in the pooled results. Approximately one in 14 patients with all-cause short stature and one in nine patients with idiopathic short stature had biopsy-confirmed CeD. Therefore, evaluation for CeD may be prudent in all patients with short stature.

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

We have read with interest the original article by Picarelli et al. [1] describing metabolic control and selected hemocoagulative/anticoagulant parameters in patients with isolated type 1 diabetes mellitus (T1DM) and in those affected by celiac disease (CD) too. According to our experience at Pediatric Endocrinology Unit of Trieste, we respectfully disagree with Picarelli’s conclusion and otherwise support the importance of a gluten-free diet (GFD). Picarelli et al. emphasize a better metabolic and glycolipidic control in patients with both DM1 and CD not following a GFD and suggest a protective role of CD in the prothrombotic state of DM1. In our opinion, their study has three critical points. First, all patients presented a glycosylated hemoglobin level (HbA1c)\7.5%. These inclusion criteria could be a selection bias that could influence the results. Second, in accord with literature, we believe that a single variable (glycosylated hemoglobin) is not sufficient to evaluate glycemic control: daily insulin dosages, hypoglycemia frequency, and glycemic variability should be also considered. Glycemic variability, specially, is considered an independent risk factor for complications [2]. Third, they do not analyze the effect of CD on the anthropometric variables nor investigate the presence of other autoimmunities. We followed up 74 patients with diabetes to evaluate the prevalence of celiac disease (CD) in a cohort of children with type 1 diabetes (T1DM) and to investigate the influence of CD on growth and metabolic control, before and after gluten-free diet (GFD). A total of 17 celiac-positive subjects (group 1) and 57 celiac-negative subjects (group 2) were examined. Data on growth and metabolic control were collected retrospectively at three different moments (diabetes diagnosis, CD diagnosis, and 6–12 months after a GFD was started). Prevalence of CD accounts for 13% of our cohort, which is comparable with prevalence in Picarelli’s cohort (13.8%). In most of cases (70%), screening test led to the diagnosis. In 70% of CD-positive patients, HbA1c levels were\8% before GFD (vs 54% of CD negative), but only in 42% of them after GFD. In CD-positive cases, good HbA1c levels were often associated with glycemic variability (65%) before GFD, while quite rarely after 6–12 months of diet (28.5%). These results allow us to suppose that before GFD was started, metabolic control was apparently good, but it really improved after GFD (reduction in glycemic variability). Besides, in our cohort, we observed that the co-occurrence of both disease compromises growth, and meanwhile, it improves after that GFD is started (BMI of CD-positive subjects rises from 46 percentile before GFD, to 54 after GFD, P \ 0.05). In our cohort, CD remains asymptomatic in the most of cases (70%), and then, the diagnosis would have been missed if the screening had not been performed, as confirmed by Picarelli’s study too. This result accords with literature [3–10] and supports importance of serological screening in diabetic population. In conclusion, we believe that serological screening is useful for diagnosing asymptomatic CD and GFD in CDpositive diabetic patients can allow growth and diabetes control comparable with patients with T1DM alone. P. Pascolo (&) E. Faleschini G. Tonini A. Ventura Institute for Child Health IRCCS Burlo Garofolo, Trieste, Italy e-mail: paolapascolo@gmail.com

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.

Subclinical celiac disease (CD) has been associated with various neurological disorders, the most common being neuropathy and cerebellar ataxia. The aims of the present study were to assess the following: 1) the prevalence of CD in patients affected by migraine; 2) whether there are regional cerebral blood flow abnormalities in migraine patients with CD compared to migraine patients without CD; and 3) the effects of a gluten free diet in migraine patients with CD. A total of 90 patients affected by idiopathic migraine were enrolled, and 236 blood donors were used as controls. Serum IgG antitransglutaminase (TgA) and IgA antiendomysial (EmA) were measured. In positive cases, diagnosis was confirmed endoscopically. A gluten free diet was started in the patients diagnosed with CD, who were followed for 6 months. A single photon emission CT brain study was performed before and after a gluten free diet. Four of 90 (4.4%; 95% CI = 1.2-11.0) migraine patients were found to have CD compared with 0.4% (95% CI = 0.01-2.3) blood donor controls (p < 0.05). During the 6 months of gluten free diet, one of the four patients had no migraine attacks, and the remaining three patients experienced an improvement in frequency, duration, and intensity of migraine. Single photon emission CT studies showed a regional baseline reduction in brain tracer uptake in all four patients. Such reduction in uptake completely resolved at follow-up. Our results suggest that a significant proportion of patients with migraine may have CD, and that a gluten free diet may lead to a improvement in the migraine in these patients.

Oesophagitis and gastro-oesophageal reflux have been implicated recently in the manifestations of coeliac disease. The aim was to investigate this association in a primary-care setting. First, the prevalence of coeliac disease was calculated in 1198 adults with oesophagitis, in 2541 adults with reflux symptoms and in 200 adults suffering from dysphagia; 5459 patients with a history consistent with dyspepsia and 709 patients with a suspicion of coeliac disease served as controls. Second, the prevalence of oesophagitis was estimated in 382 untreated and 232 treated coeliac patients; controls here comprised 5404 patients with dyspeptic symptoms and 2525 patients with reflux symptoms. Third, oesophagitis and oesophageal reflux symptoms were investigated before and after a gluten-free diet was followed in 67 adults with coeliac disease. The diagnosis of coeliac disease was based on small-bowel histology; histological exclusion of the disease was unambiguous in all controls. Oesophagitis was identified by endoscopic inspection. Altogether, 0.9% of patients with oesophagitis and 0.6% of those with oesophageal reflux symptoms had coeliac disease. The corresponding percentages were 1.0% in patients with dyspepsia and 12% with suspicion of coeliac disease. The prevalence of oesophagitis was 5.2% in untreated coeliac disease, 5.6% in treated coeliac disease, 7.0% in patients with dyspepsia, and 27% in symptomatic reflux disease. In coeliac patients, the reflux symptoms were mild but nevertheless were alleviated on a gluten-free diet. This study does not support the conception that patients with reflux oesophagitis should be screened vigorously for coeliac disease. The association between these two conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for reflux symptoms in coeliac disease.

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Its prevalence in Europe and the USA is 0.5 to 1%. To analyze epidemiological aspects and degree of compliance with gluten-free diet (GFD) among Chilean individuals with CD. Subjects with confirmed or suspected CD were invited to answer an online survey published on the web at www.fundacionconvivir.cl. The answers were reinforced with a telephone interview. The survey was answered by 1212 subjects (79% females). Median age at diagnosis was 25.8 years (range 1 to 84 years), with a bimodal curve with two peaks at less than 3 years and at 20 to 40 years of age. The diagnosis was made only by serologic markers in 9%, only by intestinal biopsy in 17.5%, and by a combination of both methods in 70%o. Conditions associated with CD were reported by 30% > of subjects and 20% > had relatives with CD. The GFD was strictly adhered to by 70% >, occasionally by 27% > and never by 3% >. Seventy five percent of subjects with a strict adherence to GFD had a favorable clinical response compared with 42% > of those with incomplete or lack of adherence (odds ratio 4.0, 95% > confidence intervals 2.8-5.7p < 0.01). In 30% of respondents, the diagnosis of CD was not confirmed according to international guidelines that require serology and duodenal biopsy. One third of subjects recognized a poor compliance with GFD. Those with a strict adherence to it had a more favorable clinical course. However, 25% > did not experience a clinical improvement despite a strict GFD, a finding which requires further study.