Causal influence of celiac disease on the risk of sarcoidosis: A Mendelian randomization study.

Observational research shows a link between celiac disease (CeD) and sarcoidosis, but the causal link between CeD and sarcoidosis is still unknown. A two-sample Mendelian randomization (MR) study was conducted to ascertain the causal connection between the 2 disorders. In our two-sample MR analysis, we identified independent genetic variants associated with CeD using publicly accessible GWAS data from people of European ancestry. Summary data for sarcoidosis were obtained from the FinnGen Consortium, the UK-Biobank, and a large GWAS dataset. To assess the association between CeD and sarcoidosis, our MR analysis used inverse variance weighted (IVW) as the primary method, incorporating the MR-Egger, weighted median (WM), and MR-PRESSO (outliers test) as a complementary method. In order to ensure that the findings were reliable, several sensitivity analyses were performed. Our study indicated that CeD had a significant causal relationship with sarcoidosis (IVW odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.07-1.20, P = 5.58E-05; WM OR = 1.12, 95% CI: 1.03-1.23, P = 1.03E-02; MR-Egger OR = 1.07, 95% CI: 0.96-1.19, P = 2.20E-01). Additionally, we obtain the same results in the duplicated datasets as well, which makes our results even more reliable. The results of this investigation did not reveal any evidence of horizontal pleiotropy or heterogeneity. Our MR analysis showed a causal effect between CeD and an elevated risk of sarcoidosis. Further study is still needed to confirm the findings and look into the processes underlying these relationships.

Prevalence of eating disorders in patients with celiac disease: a comparative study with healthy individuals.

INTRODUCTION: Celiac disease is a chronic immune-mediated disease, which is triggered and maintained by gluten in genetically susceptible individuals. Eating disorders are a persistent disturbance in eating-related behavior that results in altered food consumption or absorption and that significantly impairs physical health or psychosocial functioning. OBJECTIVE: This study aimed at evaluating the prevalence of eating disorders in Brazilian celiac patients. METHODS: This cross-sectional study was conducted as online survey including adult celiac patients who agreed to participate and a paired control health group. Questionnaires included questions about socioeconomic data and celiac disease diagnosis, and a validated questionnaire about eating disorders (Eating Attitudes Test-26. RESULTS: In total, 741 responses were studied, with 484 from the celiac group and 257 from the control group. No significant difference was observed between the number of individuals at risk of developing eating disorder (p=0.39). Both groups showed a high risk of developing eating disorders (34.2% in the celiac group and 37.7% in the control group). Furthermore, among patients with celiac disease, we found higher scores on the Eating Attitudes Test-26 in those with depression (p=0.0013), those with living difficulty due to the disease (p<0.0001), and those dissatisfied with their weight (p<0.0001). CONCLUSION: In the sample analyzed, no greater risk of eating disorders was identified in patients with celiac disease compared with the control group. However, in general, about one-third of the respondents in each group had scores associated with the risk of eating disorders. Among celiac patients, depression, difficulties living with celiac disease, and being unhappy with one's weight were associated with higher risk for eating disorder.

Relationship between vitamin D levels and pediatric celiac disease: a systematic review and meta-analysis.

BACKGROUND: The relationship between Vitamin D levels and pediatric celiac disease (CD) remains controversial. In this study, we conducted a systematic review and meta-analysis to examine the relationship between Vitamin D and pediatric CD. METHODS: We screened relevant studies from PubMed, EMBASE, and Web of Science published in English from January 1, 2000, to August 1, 2023. The included studies were assessed according to the STROBE checklist. Heterogeneity was quantified by Cochran's Q test and the I2 statistic. Publication bias was estimated by Begg's test and Egger's test. Meta-regression was used to detect potential sources of heterogeneity. RESULTS: A total of 26 studies were included in the meta-analysis. Nineteen articles compared 25(OH)D3 levels between CD patients and control groups, average 25-hydroxyvitamin D3 [25(OH)D3 or calcidiol], and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3 or calcitriol] levels, as the main forms of Vitamin D, there was a significant difference in CD patients and healthy controls (weighted mean difference (WMD) = - 5.77, 95% confidence interval (CI) = [- 10.86, - 0.69] nmol/L). Meanwhile, eleven articles reported the numbers of patients and controls with Vitamin D deficiency, there was a significant difference in the incidence of 25(OH)D3 deficiency between CD patients and healthy controls (odds ratio 2.20, 95% CI= [1.19, 4.08]). Nine articles reported changes in 25(OH)D3 levels before and after administering a GFD in patients with CD, the result of this study revealed the increase of 25(OH)D3 levels in CD patients after a gluten-free diet (GFD) (WMD = - 6.74, 95% CI = [- 9.78, - 3.70] nmol/L). CONCLUSIONS: Vitamin D levels in pediatric CD patients were lower than in healthy controls, and 25(OH)D3 deficiency was more prevalent in CD patients. We found that 25(OH)D3 levels were elevated in CD patients after GFD, which is consistent with previous research. Further well-designed, longitudinal, prospective cohort studies focusing on the role of Vitamin D in the pathogenesis of CD are therefore needed.

Prevalence and Predictors of Celiac Disease in Children With Constipation.

OBJECTIVE: To determine the prevalence of celiac disease and its predictors in children with constipation. METHODS: A hospital-based cross-sectional comparative study was conducted between November, 2018 to April, 2020. Children aged 1-12 years were screened for the presence of constipation as per ROME IV criteria and designated as cases. Age and sex matched healthy children with normal bowel habits were enrolled as comparison group. Participants underwent a detailed history and examination, and were screened for celiac disease by estimating serum anti-tissue transglutaminase IgA antibody levels (tTG-IgA). Upper gastrointestinal endoscopy and duodenal biopsy were performed in all participants who tested positive on screening (serum tTG-IgA ≥ 20 U/mL). The prevalence of celiac disease and associated factors were compared between the two groups. RESULTS: A total of 460 children (230 in each group) with mean (SD) age 64.08 (37.12) months were enrolled. Twenty-one (4.6%) children screened positive for anti tTG antibodies, among these 15 (75%) children had biopsy features suggestive of celiac disease (Marsh grade III). Children with constipation had significantly higher prevalence of celiac disease (5.65% vs 0.87%, P = 0.004) compared to children without constipation. Wasting and stunting were significantly associated with celiac disease in constipated children (P < 0.001). CONCLUSION: Children with constipation and associated growth failure have a high prevalence of celiac disease.

CT and MR Enterography in the Evaluation of Celiac Disease.

Celiac disease is a common inflammatory disease of the small bowel that induces mucosal intestinal lesions. The disease is mediated by an immune response and triggered by the ingestion of gluten in genetically predisposed individuals. Gluten contains gliadin, a component found mostly in wheat, barley, and rye. This process leads to gastrointestinal malabsorption with symptoms such as diarrhea, constipation, abdominal pain, and distention. It has a prevalence of 1%-2% in the general adult population, who present with symptoms at any age, but is more frequently found in adult women in the 3rd or 4th decade of life. Recognition of the disease has increased, but it remains a challenge to diagnose. CT and MR enterography are noninvasive studies used for evaluation of small bowel neoplasms and inflammatory small bowel pathologic conditions such as celiac disease. The authors review the spectrum of intestinal and extraintestinal findings of celiac disease at CT and MR enterography, as well as its complications, and the importance of recognizing certain imaging features that help in the diagnosis of celiac disease. More common and specific findings of celiac disease such as inversion of the jejunoileal fold pattern and mesenteric lymphadenopathy are reviewed. More uncommon entities that are more frequently associated with refractory or untreated celiac disease, such as ulcerative jejunoileitis, cavitary mesenteric lymph node syndrome, and malignancies including small bowel adenocarcinoma and lymphoma, are described. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. The slide presentation from the RSNA Annual Meeting is available for this article.

Differences in Plasma 25-Hydroxyvitamin D Levels at Diagnosis of Celiac Disease and Type 1 Diabetes.

AIM: The aim of this work is to assess the vitamin D levels, evaluated as plasma 25-hydroxyvitamin D of children with a new diagnosis of celiac disease (CD), of children with a new onset of type 1 diabetes (T1D) and in children with CD at diagnosis of T1D (T1D&CD). METHODS: In this single-center observational study, we collected data for four groups of children and adolescents: T1D, CD, T1D&CD, and a control group (CG). The CG included schoolchildren who had negative results during a mass screening campaign for CD and were not diagnosed for T1D, according to RIDI Marche registry data, were considered for the purposes of this study. Plasma 25-hydroxyvitamin D, 25(OH)D2, and 25(OH)D3 were considered as the parameters for evaluating vitamin D nutritional status, and the date of measurement was recorded to analyze vitamin D level seasonality. Vitamin D nutritional status was categorized as follows: severe deficiency (<10 ng/mL), deficiency (<20 ng/mL), insufficiency (20-29 ng/mL), or sufficiency/adequacy (≥30 ng/mL). The Kruskal-Wallis test was used to compare the groups. The association of 25(OH)D levels with health conditions and seasonal differences of 25(OH)D levels was analyzed using a multiple linear regression model. RESULTS: The number of children enrolled for the present study was 393: 131 in the CG, 131 CD, 109 T1D, and 22 T1D&CD. Significantly lower levels of vitamin D were displayed for children with CD, T1D, or both the diseases. Interestingly, severe vitamin D deficiency was detected in no children with CD, 1.5% of children in the CG, in 24.4% with T1D, and 31.8% with T1D&CD (p < 0.001). As expected, the CG children vitamin D levels were significantly influenced by seasonality. Contrarily, no seasonal differences were reported in children with CD, T1D, and T1D&CD. Multiple regression analysis showed that children with T1D and T1D&CD had lower 25(OH)D levels of 9.9 ng/mL (95% CI: 5.4; 14.5) and 14.4 ng/mL (95% CI: 6.2-22.7) compared to CG children (p < 0.001). CONCLUSIONS: Our results showed low levels of vitamin D diagnosis of T1D, CD, and T1D&CD; however, severe deficiency was only reported in children with T1D and T1D&CD. More studies are needed to better understand the role of this deficiency in children newly diagnosed with CD and T1D.

Development and validation of a brain fog scale for coeliac disease.

BACKGROUND: Brain fog is a subjective cognitive impairment commonly reported in coeliac disease. A standardised tool to define and assess it is an important unmet need. AIMS: To develop a patient-informed tool to assess brain fog in coeliac disease to support clinical care, research and drug development. METHODS: A pilot online study defined patient descriptors of brain fog. A second study evaluated the factor structure and performance of the scale across two-time points ('Now' and in the 'Past week'). One month later, participants were invited to repeat the study with two online cognitive processing tests, the Stroop task and the trail making test. RESULTS: Among adults with treated coeliac disease, 37 (91.9% F) participated in the pilot study and 510 (88.8% F) in the second study of whom 99 repeated the study 1 month later with 51 completing cognitive testing. The most common brain fog descriptors were 'difficulty focusing', 'difficulty thinking' and 'difficulty finding the right words and communicating'. The 12-item scale reflects 'cognitive impairment' and 'somatic and affective experience' and demonstrates strong psychometric properties. It tracked with patients report of brain fog being present or absent across two-time points. It did not significantly correlate with the cognitive tests. CONCLUSION: The brain fog assessment and severity scale is the first patient-informed clinical outcomes assessment tool measuring brain fog in coeliac disease. It is brief and validated for two time-based formats. Further research coupling it with biomarker discovery is needed to confirm its validity as a predictor of cognitive performance.

[Chronic diarrhoea: when is it celiac disease and when not?] / Chronische Durchfälle: Wann ist es eine Zöliakie und wann nicht?

Patients who come to clinical consultation for chronic diarrhoea (i.e., diarrhoea lasting for more than four weeks) may suffer from a wide range of clinical conditions. The possible diagnoses range from a misunderstanding of what can be considered normal and what pathological in terms of daily bowel movements, to a severe malabsorption syndrome. Since the list of possible causes of chronic diarrhoea can be puzzling, the physician's approach needs to be systematic and structured in order to allow the correct diagnosis and treatment. This article proposes an algorithm for the diagnosis of chronic diarrhoea and discusses in detail the key clinical aspects of celiac disease, which is considered a paradigmatic disease as regards chronic malabsorptive diarrhoea.

Prevalence and Predictive Factors for Celiac Disease in Children With Type 1 Diabetes: Whom and When to Screen? A Nationwide Longitudinal Cohort Study of Swedish Children.

OBJECTIVE: To examine the prevalence and predictive factors for celiac disease (CD) after a diagnosis of type 1 diabetes (T1D) in children and adolescents, to improve the current screening guidelines. RESEARCH DESIGN AND METHODS: The association between sex, age at T1D diagnosis, HLA, and diabetes autoantibodies, and a diagnosis of CD was examined in 5,295 children with T1D from the Better Diabetes Diagnosis study in Sweden. RESULTS: The prevalence of biopsy-proven CD was 9.8%, of which 58.2% already had a CD diagnosis before or at T1D onset. Almost all, 95.9%, were diagnosed with CD within 5 years after the T1D diagnosis. Younger age at the T1D diagnosis and being homozygote for DQ2 increased the risk of CD after T1D, but neither sex nor diabetes-related autoantibodies were associated with the risk. CONCLUSIONS: Age at and time after diabetes diagnosis should be considered in screening guidelines for CD in children with T1D.

Microscopic colitis found together with celiac disease in a female population is associated with one episode of lymphocytic colitis.

BACKGROUND: Microscopic colitis (MC) is considered a chronic disease associated with autoimmune disease, smoking, and drugs. The aim was to examine the association between MC and celiac disease, adjusted for smoking, considering subtypes and clinical course of the disease in a retrospectively collected female cohort. METHODS: Women (n = 240), ≤ 73 years, diagnosed as MC in medical records or pathological registers were invited. One hundred and fifty-eight women accepted to be included. Participants completed a study questionnaire about sociodemographic factors, lifestyle habits, and medical history; the Rome III questionnaire; and the visual analog scale for irritable bowel syndrome (VAS-IBS). Participants were categorized into collagenous colitis (CC) (n = 92) and lymphocytic colitis (LC) (n = 66) or MC with one episode of the disease (n = 70) and refractory MC (n = 88). Presence of IBS-like symptoms were noted. Blood samples were collected and analyzed for anti-transglutaminase antibodies. Differences between groups were calculated and logistic regression was adjusted for smoking habits. RESULTS: MC and celiac disease debuted simultaneously in half of the cases. Celiac disease was most prevalent in LC (12.1% vs. 3.3%; p = 0.05) and MC with one episode (12.9% vs. 2.3%; p = 0.01). Anti-transglutaminase antibodies were found in one patient with one episode of MC. Corticosteroid use was most often found in CC (37.0% vs. 21.2%; p = 0.037) and refractory MC (38.6% vs. 20.0%; p = 0.015). Past smokers were most prevalent in patients with one episode of MC (54.3 vs. 29.5%; p = 0.007). Current smoking was the smoking habit with highest prevalence of IBS-like symptoms. When adjusted for smoking habits, celiac disease was associated with LC (OR: 4.222; 95% CI: 1.020-17.469; p = 0.047) and tended to be inversely associated with refractory MC (OR: 0.210; 95% CI: 0.042-1.506; p = 0.058). CONCLUSION: Celiac disease is most common in patients with one episode of LC. The question remains whether LC in combination with celiac disease should be classified as celiac disease or two different entities.

Celiac disease and depressive disorders as nutritional implications related to common factors - A comprehensive review.

Celiac disease (CD) is an immune-mediated disease affecting the small intestine. The only treatment strategy for CD is the gluten-free diet (GFD). One of the more common mental disorders in CD patients is major depressive disorder (MDD). The influence of GFD on the occurrence of MDD symptoms in patients with CD will be evaluated. This diet often reduces nutritional deficiencies in these patients and also helps to reduce depressive symptoms. Both disease entities are often dominated by the same deficiencies of nutrients such as iron, zinc, selenium, iodine, or B and D vitamins. Deficiencies of particular components in CD can favor MDD and vice versa. Gluten can adversely affect the mental state of patients without CD. Also, intestinal microbiota may play an important role in the described process. This work aims to comprehensively assess the common factors involved in the pathomechanisms of MDD and CD, with particular emphasis on nutrient imbalances. Given the complexity of both disease entities, and the many common links, more research related to improving mental health in these patients and the implementation of a GFD would need to be conducted, but it appears to be a viable pathway to improving the quality of life and health of people struggling with CD and MDD. Therefore, probiotics, micronutrients, macronutrients, and vitamin supplements are recommended to reduce the risk of MDD, given that they may alleviate the symptoms of both these disease entities. In turn, in patients with MDD, it is worth considering testing for CD.

Maternal, obstetrical, and neonatal outcomes in celiac disease.

OBJECTIVES: Some studies have suggested a link between celiac disease (CD) and adverse maternal, obstetrical, and neonatal outcomes. Using a large database, we evaluated the effect of CD on pregnancy outcomes. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) of all deliveries from 2015 to 2019 in the United States. Using ICD-10 codes, we identified pregnant patients who had CD and those who did not. A multivariate logistic regression was used to generate odds ratios (ORs) with 95% confidence intervals (CIs) for maternal, obstetrical, and neonatal outcomes. RESULTS: Of 12,039,222 deliveries between 2015 and 2019, there were 10,555 births in women with CD. Pregnant women with CD were more likely to be white and older compared to those without CD. Pregnant women with CD were significantly more likely to carry a diagnosis of gestational hypertension (OR 1.26; 95% CI 1.04-1.52), preeclampsia (1.28; 1.08-1.53), and severe preeclampsia (1.62; 1.25-2.09). They were less likely to have a full-term uncomplicated delivery (OR 0.11; 95% CI, 0.05-0.20), while being more likely to require device-assisted delivery (1.25; 1.04-1.50) and sustain 3rd or 4th degree vaginal lacerations (1.56; 1.21-2.02). Babies of pregnant women with CD were more likely to be small for gestational age (SGA) (OR 1.29; 95% CI 1.03-1.61). CONCLUSIONS: CD in pregnancy appears to be associated with increased adverse maternal, obstetrical, and neonatal outcomes. Clinicians should discuss these increased risks with CD patients who are planning to conceive.

Validation of red flags in the workup of children with long-term abdominal pain - A retrospective study.

AIM: To evaluate red flags as an instrument to distinguish other medical conditions from Functional Gastrointestinal Disorders (FGID) in children with long-term abdominal pain. METHODS: In a retrospective follow-up, data were collected from 317 children who were referred for medical assessment due to long-term abdominal pain between the years 2011 and 2012 at three Swedish paediatric open clinic units in Sweden. Throughout the review of medical records, any documented red flags at the primary consultation and finally set diagnosis after 1 year were noted for all cases. RESULTS: A non-FGID disease was diagnosed in 32 cases (10.1%). The sensitivity of red flags to predict inflammatory bowel disease (IBD) was 100% and the specificity 64.1%. The sensitivity of red flags to predict celiac disease was 45.5% and the specificity 63.7%. The sensitivity of red flags to predict any non-FGID disease was 59.4%, and the specificity was 65.6%. CONCLUSION: The use of red flags is a sensitive instrument to identify patients with IBD but less applicable when identifying celiac disease and other organic diseases. Specificity is generally low and future biomarkers for assessing children with long-term abdominal pain is needed.

Evaluating CD4 and Foxp3 mRNA Expression in Tissue Specimens of Celiac Disease and Colorectal Cancer Patients.

OBJECTIVE: Celiac disease (CD) and colorectal cancer (CRC) are distinct gastrointestinal conditions with a debated association. This study aimed to evaluate the mRNA expression of CD4 and Foxp3 in tissue specimens of CD and CRC patients. The findings can provide valuable insights into the complex connection between these different gastrointestinal conditions. METHODS: Tissue samples from 100 CRC patients, 50 CD patients, and 50 healthy controls (HCs) were collected. RNA extraction, cDNA synthesis, and quantitative real-time PCR were performed. Statistical analysis was conducted using ANOVA and Pearson's correlation test. RESULT: CD4 mRNA expression was significantly higher in CRC patients compared to CD patients and HCs (P<0.0001 for both). Foxp3 mRNA expression was significantly higher in CD patients compared to CRC patients and HCs (P<0.0001 for both). Clinicopathological characteristics did not correlate significantly with gene expression levels. CONCLUSION: This study reveals differential expression patterns of CD4 and Foxp3 mRNA in CRC and CD patients. Upregulated CD4 mRNA suggests its potential role in promoting tumor growth, while increased Foxp3 mRNA expression may reflect an immunosuppressive mechanism in CD pathogenesis. These findings provide insights into the molecular and immunological aspects of CRC and CD, warranting further studies for potential therapeutic strategies.

A significant increase in anthropometric indices during long-term follow-up of pediatric patients with celiac disease, with no endocrine disorders.

Celiac disease (CeD) is likely to be associated with growth impairment and poor weight gain. However, long-term growth patterns following diagnosis are poorly characterized. We evaluated long-term anthropometric changes in a large cohort of pediatric patients with CeD. A retrospective chart review of patients diagnosed with CeD between 1999 and 2018 was conducted. Demographic and clinical data were collected, and anthropometrics were analyzed from diagnosis and throughout follow-up. The study included 500 patients (59.8% females, median (IQR) age at diagnosis 5.7 (3.7-8.9) years), with a mean follow-up of 5.5 (range 1.5-16.2) years. Weight, height, and BMI Z-score-for-age (WAZ, HAZ, and BMIZ) increased significantly from a mean (± SD) of - 0.82 (± 1.21), - 0.73 (± 1.16), and - 0.32 (± 1.11) at diagnosis to - 0.41 (± 1.23), - 0.45(± 1.16), and - 0.17 (± 1.14) at last follow-up, respectively (p < 0.001 for WAZ and HAZ and p = 0.002 for BMIZ). The largest improvements were observed in patients diagnosed before 3 years of age (p < 0.01). Patients for whom the final adult height was available (n = 86) improved from HAZ mean (± SD) - 0.89 ± 1.37 at diagnosis to - 0.51 ± 1.28 at adulthood measurement, p < 0.05. Wasting was present in 19.7% and stunting in 16.4% of the cohort at diagnosis and normalized in 77.3% and 64.8%, respectively, within a median (IQR) time of 0.79 (0.42-4.24) and 2.3 (0.72-6.02) years, respectively. Gluten-free diet adherence and frequency of visits were not associated with normalization of wasting or stunting in all age groups.  Conclusion: Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. Younger age at diagnosis is associated with greater improvement in weight and linear growth, emphasizing the importance of early diagnosis of CeD. What is Known: • Celiac disease (СeD) is likely to be associated with growth impairment and poor weight gain. • Long-term changes in anthropometric indices after diagnosis of CeD are not well characterized. What is New: • Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. • Young age at diagnosis is associated with larger improvement in weight and linear growth.

Prevalence of celiac-related antibodies and its impact on metabolic control in Egyptian children with type 1 diabetes mellitus.

OBJECTIVE: The simultaneous presence of celiac disease and type 1 diabetes (T1DM) is coupled with more hazards of comorbidities and complications. This current study aimed to screen for celiac disease in Egyptian children with type 1 diabetes and evaluate its impact on glycemic control. METHODS: A cross-sectional study was verified with 200 Egyptian children diagnosed with T1DM and having a diabetic duration of less than five years. Testing for anti-tissue transglutaminase IgA (tTG-IgA), anti-tissue transglutaminase IgG (tTG-IgG), anti-Endomysial IgA (EMA), and Hb A1c levels were done. RESULTS: The serological screening revealed that 11 cases (5.5%) tested positive; 8 children with T1DM (4.0%) showed tTG-IgA antibodies ≥ 10 times the upper limit of normal (ULN) with at least one symptom; and 3 cases (1.5%) had levels between 20 and 50 IU/ml (considering a cut-off point of 10 U/ML for positive results). Intestinal biopsy was performed for these three cases, with one case detected to have subtotal villous atrophy, resulting in an overall prevalence of celiac disease in T1DM as 4.5%. Children with positive screening exhibited a higher insulin dose, a higher HbA1c, an increased frequency of hypoglycemic attacks, and recurrent DKA compared to negative cases. A negative correlation was detected between tTG-IgA antibodies with height Z score and hemoglobin level, while a positive correlation was found between tTG-IgA antibodies and HbA1c level. CONCLUSION: Undiagnosed celiac disease in children with T1DM negatively impacted metabolic control and affected their general health.

Prevalence of coeliac disease in patients with systemic lupus erythematosus: a systematic review and meta-analysis.

BACKGROUND: There is some evidence of a higher prevalence of coeliac disease (CD) among patients with SLE than in the general population. However, the prevalence estimates vary substantially. OBJECTIVE: To investigate the prevalence of CD among patients with SLE through systematic review and meta-analysis. METHODS: We performed searches in the databases of Medline, Embase, Cochrane and Web of Science Core Collection between 1 January 1990 and 9 July 2023. A total of 2053 publications were rendered in the searches, of which 68 were reviewed in full text and 14 included in the analyses. Primary analysis estimated the pooled prevalence of biopsy-verified CD in patients with SLE. In the secondary analysis, the prevalence of serological markers indicative of CD was investigated. The quality of studies was appraised using the Joanna Briggs Institute Critical Appraisal Tool. We conducted meta-regression analyses to investigate associations between the prevalence of CD in individuals with SLE and publication year, study population size, CD prevalence in the general population, proportion of females and quality assessment score. RESULTS: A total of 14 studies met the inclusion criteria, of which 11 were included in the primary analysis of biopsy-verified CD. Among 1238 patients with SLE, 14 had CD. The weighted pooled prevalence of CD was 0.7% (95% CI 0.0 to 1.8). The weighted pooled prevalence of CD serological markers in 1063 patients with SLE was 3.7% (95% CI 1.4 to 6.7). In meta-regression analyses, no associations between CD prevalence and study characteristics, demographics and quality assessment scores were found. CONCLUSIONS: In this meta-analysis, we found a weighted pooled prevalence of biopsy-verified CD in patients with SLE comparable with the prevalence in the general population. Our findings do not support routine screening for CD in patients with SLE. However, individual screening could be considered in cases of clinical suspicion and additional risk factors for CD. PROSPERO REGISTRATION NUMBER: CRD42022339594.

Genotypes predisposing for celiac disease and autoimmune diabetes and risk of infections in early childhood.

OBJECTIVES: Infections in early childhood have been associated with risk of celiac disease (CD) and type 1 diabetes (T1D). We investigated whether this is driven by susceptibility genes for autoimmune disease by comparing infection frequency by genetic susceptibility variants for CD or T1D. METHODS: We genotyped 373 controls and 384 children who developed CD or T1D in the population-based Norwegian Mother, Father and Child Cohort study (MoBa) study for human leukocyte antigen (HLA)-DQ, FUT2, SH2B3, and PTPN22, and calculated a weighted non-HLA genetic risk score (GRS) for CD and T1D based on over 40 SNPs. Parents reported infections in questionnaires when children were 6 and 18 months old. We used negative binomial regression to estimate incidence rate ratio (IRR) for infections by genotype. RESULTS: HLA genotypes for CD and T1D or non-HLA GRS for T1D were not associated with infections. The non-HLA GRS for CD was associated with a nonsignificantly lower frequency of infections (aIRR: 0.95, 95% CI: 0.87-1.03 per weighted allele score), and significantly so when restricting to healthy controls (aIRR: 0.89, 0.81-0.99). Participants homozygous for rs601338(A;A) at FUT2, often referred to as nonsecretors, had a nonsignificantly lower risk of infections (aIRR: 0.91, 95% CI: 0.83-1.01). SH2B3 and PTPN22 genotypes were not associated with infections. The association between infections and risk of CD (OR: 1.15 per five infections) was strengthened after adjustment for HLA genotype and non-HLA GRS (OR: 1.24). CONCLUSIONS: HLA variants and non-HLA GRS conferring susceptibility for CD were not associated with increased risk of infections in early childhood and is unlikely to drive the observed association between infections and risk of CD or T1D in many studies.

Systematic review with meta-analysis: Cause-specific and all-cause mortality trends across different coeliac disease phenotypes.

BACKGROUND: Data on mortality in coeliac disease are contrasting. AIMS: To systematically review the literature on all-cause and cause-specific mortality in coeliac disease compared to the general population, and evaluate differences across clinical phenotypes, geographical regions, and over time. METHODS: We searched PubMed and Embase from 1 January 1970 to 31 December 2022 for eligible studies reporting on all-cause and cause-specific mortality in coeliac disease compared to the general population or controls. The protocol was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/852DN). RESULTS: We included 25 studies. All-cause mortality (HR 1.16, 95% CI 1.05-1.27, I2 = 89%), mortality due to malignancies (HR 1.21, 95% CI 1.08-1.36, I2 = 65%) and respiratory disease (HR 1.39, 95% CI 1.04-1.86, I2 = 76%) were increased. Mortality due to non-Hodgkin lymphoma (HR 10.14, 95% CI 2.19-46.88, I2 = 96%) was markedly increased. Mortality significantly decreased in recent decades: 1989-2004 (HR 1.61, 95% CI 1.27-2.03, I2 = 91%), 2005-2014 (HR 1.16, 95% CI 0.99-1.36, I2 = 89%), 2015-2022 (HR 1.19, 95% CI 1.05-1.35, I2 = 93%). All-cause mortality was not increased in dermatitis herpetiformis (HR 0.85, 95% CI 0.73-0.99, I2 = 40%) and undiagnosed coeliac disease (HR 1.09, 95% CI 0.95-1.25, I2 = 0%). Mortality was increased in the UK (HR 1.23, 95% CI 1.03-1.47, I2 = 91%) but not Scandinavia (HR 1.01, 95% CI 0.91-1.13, I2 = 81%). Limitations include high heterogeneity and lack of data for many countries. CONCLUSION: Mortality in coeliac disease is increased, predominantly due to malignancies-particularly non-Hodgkin lymphoma-although differing significantly across disease phenotypes. Mortality of patients with coeliac disease has significantly decreased in recent decades. These results may influence diagnosis and management.