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INTRODUCTION: Celiac disease is an autoimmune condition that affects approximately 1% of the population worldwide. Although its main impact often concerns the small intestine, resulting in villous atrophy and nutrient malabsorption, it can also cause systemic manifestations, particularly when undiagnosed or left untreated. METHOD: Attention is directed to the possible psychological, psychiatric, and organic brain manifestations of celiac disease. Specific topics related to the influence and risk of such manifestations with respect to celiac disease are defined and discussed. Overall, eighteen main topics are considered, sifted from over 500 references. RESULTS: The most often studied topics were found to be the effect on quality of life, organic brain dysfunction and ataxia, epilepsy, Down syndrome, generalized psychological disorders, eating dysfunction, depression, and schizophrenia. For most every topic, although many studies report a connection to celiac disease, there are often one or more contrary studies and opinions. A bibliographic analysis of the cited articles was also done. There has been a sharp increase in interest in this research since 1990. Recently published articles tend to receive more referencing, up to as many as 15 citations per year, suggesting an increasing impact of the topics. The number of manuscript pages per article has also tended to increase, up to as many as 12 pages. The impact factor of the publishing journal has remained level over the years. CONCLUSION: This compendium may be useful in developing a consensus regarding psychological, psychiatric, and organic brain manifestations that can occur in celiac disease and for determining the best direction for ongoing research focus.
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AIMS/HYPOTHESIS: While the association between coeliac disease and type 1 diabetes is well documented, the association of coeliac disease with type 2 diabetes risk remains undetermined. We conducted a nationwide cohort and Mendelian randomisation analysis to investigate this link. METHODS: This nationwide matched cohort used data from the Swedish ESPRESSO cohort including 46,150 individuals with coeliac disease and 219,763 matched individuals in the comparator group selected from the general population, followed up from 1969 to 2021. Data from 9053 individuals with coeliac disease who underwent a second biopsy were used to examine the association between persistent villous atrophy and type 2 diabetes. Multivariable Cox regression was employed to estimate the associations. In Mendelian randomisation analysis, 37 independent genetic variants associated with clinically diagnosed coeliac disease at p<5×10-8 were used to proxy genetic liability to coeliac disease. Summary-level data for type 2 diabetes were obtained from the DIAGRAM consortium (80,154 cases) and the FinnGen study (42,593 cases). RESULTS: Over a median 15.7 years' follow-up, there were 6132 (13.3%) and 30,138 (13.7%) incident cases of type 2 diabetes in people with coeliac disease and comparator individuals, respectively. Those with coeliac disease were not at increased risk of incident type 2 diabetes with an HR of 1.00 (95% CI 0.97, 1.03) compared with comparator individuals. Persistent villous atrophy was not associated with an increased risk of type 2 diabetes compared with mucosal healing among participants with coeliac disease (HR 1.02, 95% CI 0.90, 1.16). Genetic liability to coeliac disease was not associated with type 2 diabetes in DIAGRAM (OR 1.01, 95% CI 0.99, 1.03) or in FinnGen (OR 1.01, 95% CI 0.99-1.04). CONCLUSIONS/INTERPRETATION: Coeliac disease was not associated with type 2 diabetes risk.
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Enfermedad Celíaca , Diabetes Mellitus Tipo 2 , Análisis de la Aleatorización Mendeliana , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Enfermedad Celíaca/genética , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Suecia/epidemiología , Adulto , Estudios de Cohortes , Anciano , Factores de Riesgo , Predisposición Genética a la Enfermedad , Adolescente , Adulto JovenRESUMEN
BACKGROUND: Patients on a gluten-free diet (GFD) whose celiac disease (CD) status is unknown may undergo gluten challenge (GC) to clarify their diagnosis. Though this is an established diagnostic practice, the proportion of patients undergoing GC who are diagnosed with CD is unknown. AIMS: We aimed to analyze which factors were predictive of having CD in a cohort of patients who underwent GC followed by upper endoscopy with duodenal biopsy. METHODS: We identified adult patients at a CD referral center who had been on a GFD and then underwent GC to determine a diagnosis of CD during the years spanning 2006 to 2020. We compared those patients found to have CD (defined as villus atrophy/Marsh 3) on duodenal biopsy with those who did not, using the chi square and Fischer exact tests. RESULTS: We identified 206 patients who underwent GC. Of these 206, 30 (14%) were diagnosed with CD based on post-GC duodenal biopsy. 176 of the 206 (85%) patients reported various gastrointestinal symptoms, including bloating (39%), though these were more common in those without CD (any GI symptoms: 89% vs 67%, p 0.004; bloating: 43% vs 20%, p 0.019). Serology values, when normalized, including pre- and post-challenge TTG IgA (37% vs 1.7%, p 0.001; 23% versus 2.3%, p 0.001), DGP IgG and IgA (57% vs 2.8%, p 0.001; 37% vs 6.2%, p 0.001) were higher in the group of patients with CD. CONCLUSION: Among patients undergoing GC for diagnostic purposes, only 14% had evidence of villus atrophy corresponding with CD on duodenal biopsy. The presence of any elevated pre-challenge serology was associated with CD. Bloating in combination with low serologies may help risk stratify patients as being less likely to have CD upon GC.
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Enfermedad Celíaca , Dieta Sin Gluten , Duodeno , Glútenes , Humanos , Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Duodeno/patología , Glútenes/efectos adversos , Glútenes/administración & dosificación , Glútenes/inmunología , Biopsia , Anciano , Estudios RetrospectivosRESUMEN
Background: Celiac disease (CeD) is associated with several immune-mediated disorders, but it is unclear whether it is associated with eosinophilic esophagitis (EoE). Objective: We sought to examine the risk of EoE in patients with biopsy-verified CeD compared with matched controls and siblings. Methods: Using nationwide population-based histopathology data, we identified 27,338 patients with CeD diagnosed in the period 2002 to 2017 in Sweden. Patients with CeD were age- and sex-matched with up to 5 reference individuals (n = 134,987) from the general population. Cox Regression was used to estimate hazard ratios (HRs) for developing biopsy-verified EoE. In a secondary analysis, we used unaffected siblings of patients with CeD as comparators to adjust for intrafamilial confounding. Results: The median age at CeD diagnosis was 27 years, and 63.3% were female patients. During a median follow-up of 8.1 years, 17 patients with CeD and 13 matched reference individuals were diagnosed with EoE. This corresponded to incidence rates of 0.08 versus 0.01 per 1000 person-years, respectively, and an adjusted HR for EoE of 6.65 (95% CI, 3.26-13.81). Compared with their siblings without CeD, patients with CeD were however at a no increased risk of EoE (HR, 1.39; 95% CI, 0.55-3.51). Conclusions: In this study, individuals with CeD were at a 6.6-fold increased risk of later EoE compared with the general population. This association might be explained by an altered health-seeking behavior or through shared genetic or early environmental factors because the excess risk disappeared in sibling analyses.
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BACKGROUND & AIMS: The aim of this study was to determine the risk of irritable bowel syndrome (IBS) diagnosis in patients with celiac disease (CD) compared with general population comparators. METHODS: Using Swedish histopathology and register-based data, we identified 27,262 patients with CD diagnosed in 2002-2017 and 132,922 age- and sex-matched general population comparators. Diagnoses of IBS were obtained from nationwide inpatient and non-primary outpatient records. Cox regression estimated hazard ratios (aHRs) for IBS adjusted for education level and Charlson Comorbidity Index. To reduce potential surveillance bias our analyses considered incident IBS diagnosis ≥1 year after CD diagnosis. Using conditional logistic regression, secondary analyses were calculated to estimate odds ratios (ORs) for IBS diagnosis ≥1 year before CD diagnosis. RESULTS: During an average of 11.1 years of follow-up, 732 celiac patients (2.7%) were diagnosed with IBS vs 1131 matched general population comparators (0.9%). Overall (≥1-year of follow-up), the aHR for IBS was 3.11 (95% confidence interval [CI], 2.83-3.42), with aHR of 2.00 (95% CI, 1.63-2.45) after ≥10 years of follow-up. Compared with siblings (n = 32,010), celiac patients (n = 19,211) had ≥2-fold risk of later IBS (aHR, 2.42; 95% CI, 2.08-2.82). Compared with celiac patients with mucosal healing, those with persistent villus atrophy on follow-up biopsy were less likely to be diagnosed with IBS (aHR, 0.66; 95% CI, 0.46-0.95). CD was also associated with having an earlier IBS diagnosis (OR, 3.62; 95% CI, 3.03-4.34). CONCLUSIONS: In patients with CD, the risk of IBS is increased long before and after diagnosis. Clinicians should be aware of these long-term associations and their implications on patient management.
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Enfermedad Celíaca , Síndrome del Colon Irritable , Humanos , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/epidemiología , Síndrome del Colon Irritable/epidemiología , Síndrome del Colon Irritable/complicaciones , Femenino , Masculino , Suecia/epidemiología , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Adolescente , Estudios de Cohortes , Incidencia , Factores de Riesgo , NiñoRESUMEN
BACKGROUND: Predominantly antibody deficiency (PAD) is associated with noninfectious inflammatory gastrointestinal disease. Population estimates of celiac disease (CeD) risk in those with PAD are limited. OBJECTIVE: To estimate population risk of PAD in individuals with CeD. METHODS: We conducted a nationwide case-control study in Swedish individuals who received a diagnosis of CeD between 1997 and 2017 (n = 34,980), matched to population comparators by age, sex, calendar year, and county. The CeD was confirmed through the Epidemiology Strengthened by histopathology Reports in Sweden study, which provided information on biopsy specimens from each of Sweden's pathology departments. PAD was identified using International Classification of Diseases, 10th Revision coding and categorized according to the International Union of Immunologic Societies. Logistic regression was used to calculate adjusted odds ratios (aORs) and 95% CIs. RESULTS: PAD was more prevalent in CeD than in population controls (n = 105 [0.3%] vs n = 57 [0.033%], respectively). This translated to an aOR of 8.23 (95% CI 5.95-11.48). The association was strongest with common variable immunodeficiency (aOR 17.25; 95% CI 6.86-52.40), and slightly lower in other PAD (aOR 8.39; 95% CI 5.79-12.32). The risk of CeD remained increased at least 5 years after diagnosis of PAD (aOR 4.79; 95% CI 2.89-7.97, P-heterogeneity ≤ 0.001). CONCLUSION: PAD was associated with an increased risk of CeD. A particularly strong association was seen in those with CVID, although this should be interpreted cautiously given the limited understanding of the mechanisms of histopathologic changes in these patients.
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Enfermedad Celíaca , Humanos , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/complicaciones , Suecia/epidemiología , Estudios de Casos y Controles , Femenino , Masculino , Adulto , Persona de Mediana Edad , Anciano , Adolescente , Adulto Joven , Niño , Preescolar , Inmunodeficiencia Variable Común/epidemiología , Inmunodeficiencia Variable Común/complicaciones , Prevalencia , Lactante , Oportunidad Relativa , Factores de RiesgoRESUMEN
BACKGROUND: Coeliac disease (CeD) has been associated with a broad range of diseases in observational data; however, whether these associations are causal remains undetermined. We conducted a phenome-wide Mendelian randomization analysis (MR-PheWAS) to investigate the comorbidities of CeD. METHODS: Single nucleotide polymorphisms (SNPs) associated with CeD at the genome-wide significance threshold and without linkage disequilibrium (R2 <0.001) were selected from a genome-wide association study including 12,041 CeD cases as the instrumental variables. We first constructed a polygenic risk score for CeD and estimated its associations with 1060 unique clinical outcomes in the UK Biobank study (N = 385,917). We then used two-sample MR analysis to replicate the identified associations using data from the FinnGen study (N = 377,277). We performed a secondary analysis using a genetic instrument without extended MHC gene SNPs. FINDINGS: Genetic liability to CeD was associated with 68 clinical outcomes in the UK Biobank, and 38 of the associations were replicated in the FinnGen study. Genetic liability to CeD was associated with a higher risk of several autoimmune diseases (type 1 diabetes and its complications, Graves' disease, Sjögren syndrome, chronic hepatitis, systemic and cutaneous lupus erythematosus, and sarcoidosis), non-Hodgkin's lymphoma, and osteoporosis and a lower risk of prostate diseases. The associations for type 1 diabetes and non-Hodgkin's lymphoma attenuated when excluding SNPs in the MHC region, indicating shared genetic aetiology. INTERPRETATION: This study uncovers multiple clinical outcomes associated with genetic liability to CeD, which suggests the necessity of comorbidity monitoring among this population. FUNDING: This project was funded by Karolinska Institutet and the Swedish Research Council.
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OBJECTIVES: Celiac disease (CeD) has been linked to an increased risk of other autoimmune diseases, yet the impact of delayed CeD diagnosis on risk of developing additional autoimmune diseases remains uncertain. We investigated this through a nationwide matched case-control study. METHODS: Using the ESPRESSO cohort with histophatology data from Sweden's 28 pathology departments, we assessed 46,575 biopsy-confirmed CeD cases from 1964 to 2017. We extracted 225,295 matched controls without histopathology information from the Swedish Total Population Register. Autoimmune disease was defined through diagnostic codes in the National Patient Register. Through conditional logistic regression we estimated odds ratio (OR) of autoimmune disease up until CeD diagnosis/matching date comparing CeD cases to controls across different age strata. RESULTS: A total of 3059 (6.6 %) CeD patients and 4076 (1.8 %) controls had earlier autoimmune disease. The overall OR for autoimmune disease in CeD was 3.50 (95%CI 3.32-3.70). The risk of autoimmune disease did not escalate with increasing age at CeD diagnosis. Compared with controls, the OR of autoimmune disease in CeD patients was 7.70 (95%CI 4.71-12.57) in those diagnosed with CeD in 0-4 years, 19.02 (95%CI 13.80-26.23) in 5-9 years, 6.18 (95%CI 5.14-7.44) in 10-14 years, 4.80 (95%CI 3.97-5.79) in 15-19 years, 4.24 (95%CI 3.55-5.07) in 20-29 years, 4.65 (95%CI 3.93-5.51) in 30-39 years, 3.67 (95%CI 3.30-4.09) in 40-59 years, and 1.67 (95%CI 1.50-1.85) in ≥60 years. CONCLUSIONS: This study revealed an increased risk of autoimmune disease among CeD patients compared with controls. However, older age at CeD diagnosis did not seem to escalate the risk of autoimmune diseases.
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Enfermedades Autoinmunes , Enfermedad Celíaca , Humanos , Anciano , Estudios de Casos y Controles , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/patología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/epidemiología , Modelos Logísticos , BiopsiaRESUMEN
BACKGROUND: The diagnosis of celiac disease (CD) is based on positive IgA autoantibodies to tissue transglutaminase (TTG IgA) and confirmatory histopathology demonstrating duodenal villus atrophy (VA). Diagnostic challenges can occur when VA is found on duodenal biopsies in patients without prior CD serologies. AIMS: To characterize the predictors of CD seropositivity in patients with VA on biopsy without prior CD serologies. METHODS: We performed a retrospective cohort study of patients found to have duodenal VA on histopathology from 2010 to 2020 who did not have prior CD serologies measured and who had them checked after their biopsy. Patients with known or suspected CD prior to their duodenal biopsy were excluded. RESULTS: Of 162 patients with VA and no prior CD serologies, 50 (31%) subsequently had an elevated TTG IgA consistent with CD. Patients with an elevated TTG IgA were more likely to be non-Hispanic (76% vs. 42%; p < 0.001), white (74% vs. 62%; p = 0.025), and younger (ages 18-39, 26% vs. 12%; p = 0.002) compared to those with a negative TTG IgA. By contrast, these patients were less likely to present in middle adulthood (ages 40-59, 6% vs. 29%; p = 0.002). The most common identified etiologies of seronegative VA were Crohn's disease (13%), seronegative CD (8.9%), H. pylori infection (6.3%), tropical sprue (5.4%), and olmesartan-related enteropathy (3.6%). CONCLUSION: Age and ethnicity may be helpful when stratifying the likelihood of CD in the absence of supporting serologies. A majority of patients (69%) diagnosed with VA without prior CD serologies have negative serologies, consistent with seronegative CD or the spectrum of non-celiac enteropathies for which further evaluation is needed.
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Enfermedad Celíaca , Anomalías del Sistema Digestivo , Humanos , Adulto , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Estudios Retrospectivos , Transglutaminasas , Duodeno/patología , Biopsia , Autoanticuerpos , Endoscopía Gastrointestinal , Inmunoglobulina A , Atrofia/patologíaRESUMEN
INTRODUCTION: Persistent villous atrophy (VA) is not uncommon in celiac disease (CeD) while patients take a gluten-free diet (GFD). METHODS: We conducted a retrospective study with 122 serum samples collected from controls and patients with CeD either at the initial diagnosis or at the follow-up during endoscopy. These samples were assigned to 3 groups: nonceliac control, non-VA CeD (Marsh score 0-2), and VA CeD (Marsh score 3a-3c). We established an in-house multiplex assay to identify potential serological biomarkers for VA. We assessed autoantibodies reported to affect the small intestine, including IgA and IgG antibodies against tissue transglutaminase (tTG), interferons, villin, actin, autoimmune enteropathy-related 75 kDa antigen (AIE-75), and tryptophan hydroxylase (TPH)-1, as well as 27 cytokines. The apolipoproteins quantified included apo A1, apo B-100, and apo A4, which were produced predominantly by the intestinal epithelium or expressed specifically in villi. RESULTS: Autoantibody levels were high only for tTG antibodies, which performed well in initial CeD diagnosis, but suboptimally for VA prediction during follow-up, because 14.6% of the follow-up patients with VA had low tTG-IgA. Increasing dilution improved tTG-IgA quantification, particularly when the antibody levels were extremely high but did not significantly improve VA detection. Among those with low tTG-IgA and persistent VA, high proinflammatory cytokines were observed in 2 patients. Median low-density lipoprotein cholesterol levels were significantly lower in the VA CeD group ( P = 0.03). Apolipoprotein levels were similar in patients with and without VA but diverged between those on a GFD or not. DISCUSSION: tTG-IgA as a biomarker is suboptimal for VA prediction while on a GFD. Persistent VA is associated with low low-density lipoprotein cholesterol levels and partially related to persistent high proinflammatory cytokines.
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Enfermedad Celíaca , Humanos , Estudios Retrospectivos , Transglutaminasas , Biomarcadores , Autoanticuerpos , Inmunoglobulina A , Atrofia , Citocinas , Lipoproteínas LDL , ColesterolRESUMEN
Celiac disease (CD) is an autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4+ T cell activation culminates in intraepithelial T cell (T-IEL)-mediated intestinal damage remain unclear. Here, we performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different CD states and healthy controls. Untreated, active, and potential CD were associated with an enrichment of activated intestinal T cell populations, including CD4+ follicular T helper (TFH) cells, regulatory T cells (Tregs), and natural CD8+ αß and γδ T-IELs. Natural CD8+ αß and γδ T-IELs expressing activating natural killer cell receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. After gluten ingestion, both αß and γδ T cell clones from this memory population of T-IELs circulated systemically along with gluten-specific CD4+ T cells and assumed a cytotoxic and activating NKR-expressing phenotype. Collectively, these findings suggest that cytotoxic T cells in CD are rapidly mobilized in parallel with gluten-specific CD4+ T cells after gluten ingestion.
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Enfermedad Celíaca , Linfocitos Intraepiteliales , Humanos , Glútenes , Linfocitos T Citotóxicos , InflamaciónRESUMEN
The etiology and mechanism of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are poorly understood and no biomarkers have been established. Specifically, the relationship between the immunologic, metabolic, and gastrointestinal abnormalities associated with ME/CFS and their relevance to established symptoms of the condition remain unclear. Relying on data from two independent pairs of ME/CFS and control cohorts, one at rest and one undergoing an exercise challenge, we identify a state of suppressed acute-phase innate immune response to microbial translocation in conjunction with a compromised gut epithelium in ME/CFS. This immunosuppression, along with observed enhancement of compensatory antibody responses to counter the microbial translocation, was associated with and may be mediated by alterations in glucose and citrate metabolism and an IL-10 immunoregulatory response. Our findings provide novel insights into mechanistic pathways, biomarkers, and potential therapeutic targets in ME/CFS, including in the context of exertion, with relevance to both intestinal and extra-intestinal symptoms.
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Celiac disease (CD) is a chronic autoimmune disorder that affects the small intestine in genetically predisposed individuals. Previous studies have investigated the potential link between CD and cardiovascular disease (CVD); however, the findings have been inconsistent. We aimed to provide an updated review of the literature on the association between CD and CVD. PubMed was searched from inception to January 2023 using keywords including CD, cardiovascular disease, coronary artery disease, cardiac arrhythmia, heart failure, cardiomyopathy, and myocarditis. We summarized the results of the studies, including meta-analyses and original investigations, and presented them according to the different forms of CVD. Meta-analyses published in 2015 provided mixed results regarding the relationship between CD and CVD. However, subsequent original investigations have shed new light on this association. Recent studies indicate that individuals with CD are at a higher risk of developing overall CVD, including an increased risk of myocardial infarction and atrial fibrillation. However, the link between CD and stroke is less established. Further research is needed to determine the link between CD and other cardiac arrhythmias, such as ventricular arrhythmia. Moreover, the relationship between CD and cardiomyopathy or heart failure, as well as myopericarditis, remains ambiguous. CD patients have a lower prevalence of traditional cardiac risk factors, such as smoking, hypertension, hyperlipidemia, and obesity. Therefore, it is important to discover strategies to identify patients at risk and reduce the risk of CVD in CD populations. Lastly, it is unclear whether adherence to a gluten-free diet can diminish or increase the risk of CVD among individuals with CD, necessitating further research in this area. To fully comprehend the correlation between CD and CVD and to determine the optimal prevention strategies for CVD in individuals with CD, additional research is necessary.
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Enfermedades Cardiovasculares , Enfermedad Celíaca , Insuficiencia Cardíaca , Hipertensión , Miocarditis , Humanos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/epidemiología , Hipertensión/complicaciones , Factores de Riesgo , Arritmias Cardíacas/etiología , Arritmias Cardíacas/complicaciones , Miocarditis/complicaciones , Insuficiencia Cardíaca/complicacionesRESUMEN
INTRODUCTION: Several earlier studies have indicated an increased risk of cardiac birth defects among infants born to mothers with celiac disease (CeD). Through linking nationwide Swedish health care registries, we aimed to investigate maternal CeD and risk of any or cardiac birth defects in their offspring. METHODS: We performed a retrospective cohort study of infants born between 2002 and 2016 to women with biopsy-proven CeD (villous atrophy, Marsh III) matched to infants born to nonceliac women from the general population. Conditional logistic regression with odds ratios (OR) and their 95% confidence intervals (CI) was used to determine the association between maternal CeD and birth defects. To minimize the impact of intrafamilial confounding, we also compared infants born to mothers with CeD with infants born to their nonaffected sisters. RESULTS: A total of 6,990 infants were born to mothers with diagnosed CeD compared with 34,643 infants born to reference mothers. Any birth defect was seen in 234 (33 per 1,000 infants) and 1,244 (36/1,000) reference infants corresponding to an OR of 0.93 (95% CI 0.81-1.08). Cardiac birth defects were seen in 113 (16/1,000) vs 569 (16/1,000) infants (OR 0.98, 95% CI 0.80-1.20). Similar OR for any and cardiac birth defects were also seen in sibling comparisons. DISCUSSION: We found no statistically significant risk of any or cardiac birth defects in infants born to mothers with diagnosed CeD compared with the general population and to their nonaffected sisters.
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Enfermedad Celíaca , Madres , Lactante , Humanos , Femenino , Estudios Retrospectivos , Enfermedad Celíaca/epidemiología , Hermanos , Suecia/epidemiologíaRESUMEN
BACKGROUND: The only treatment for celiac disease (CeD) is strict lifelong adherence to a gluten-free diet (GFD). In some individuals the demands of a GFD may contribute to maladaptive eating attitudes and behaviors that impair quality of life (QOL). The Celiac Disease Food Attitudes and Behaviors (CD-FAB) is an easily administered and scored 11-item tool querying potentially maladaptive food attitudes and behaviors resulting from beliefs around gluten exposures and food safety. OBJECTIVES: To assess the usefulness of the CD-FAB in establishing the presence of maladaptive food attitudes and behaviors among adults with CeD and to explore the relationship between these attitudes and behaviors and other factors including QOL, anxiety, depression, CeD symptoms and personality traits. METHODS: The study is a cross-sectional pilot of 50 adults (mean age 29.6 years) with biopsy-proven CeD who followed a GFD for at least one year and had no self-reported eating disorder diagnosis. High scores on the CD-FAB tool suggest higher disordered eating attitudes and beliefs. RESULTS: Compared to lower scores (mean 20.2), higher (worse) CD-FAB scores (mean 54.5) were positively associated with recency of diagnosis, number of CeD-related gastrointestinal symptoms, and the personality trait of neuroticism. Higher CD-FAB scores were statistically and clinically significantly associated with diminished QOL (p < 0.001). The relationship with anxiety and depression was less clear but trended in the expected direction. CONCLUSION: The CD-FAB may be a useful tool for dietitians who wish to monitor maladaptive food attitudes and behaviors among their CeD patients, especially in the first-year post-diagnosis.
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Enfermedad Celíaca , Calidad de Vida , Adulto , Humanos , Enfermedad Celíaca/diagnóstico , Estudios Transversales , Cooperación del Paciente , Actitud , Dieta Sin GlutenRESUMEN
BACKGROUND: An association has been reported between celiac disease (CD) and microscopic colitis (MC). However, large, population-based cohort studies are rare. OBJECTIVE: To systematically examine the association between CD and MC in a large, nationwide cohort. METHODS: We conducted a nationwide population-based matched cohort study in Sweden of 45,138 patients with biopsy-verified CD (diagnosed in 1990-2016), 223,149 reference individuals, and 51,449 siblings of CD patients. Data on CD and MC were obtained from all (n = 28) pathology departments in Sweden. Adjusted hazard ratios (aHRs) were calculated using Cox regression. RESULTS: During follow-up, 452 CD patients and 197 reference individuals received an MC diagnosis (86.1 vs. 7.5 per 100,000 person-years). This difference corresponded to an aHR of 11.6 (95% confidence interval [CI] = 9.8-13.8) or eight extra MC cases in 1000 CD patients followed up for 10 years. Although the risk of MC was highest during the first year of follow-up (aHR 35.2; 95% CI = 20.1-61.6), it remained elevated even after 10 years (aHR 8.1; 95% CI = 6.0-10.9). Examining MC subtypes lymphocytic colitis (LC) and collagenous colitis (CC) separately, the aHR was 12.4 (95% CI = 10.0-15.3) for LC and 10.2 (95% CI = 7.7-13.6) for CC. MC was also more common before CD (adjusted odds ratio [aOR] = 52.7; 95% CI = 31.4-88.4). Compared to siblings, risk estimates decreased but remained elevated (CD and later MC: HR = 6.2; CD and earlier MC: aOR = 7.9). CONCLUSION: Our study demonstrated a very strong association of MC with CD with an increased risk of future and previous MC in CD patients. The magnitude of the associations underscores the need to consider the concomitance of these diagnoses in cases in which gastrointestinal symptoms persist or recur despite a gluten-free diet or conventional MC treatment. The comparatively lower risk estimates in sibling comparisons suggest that shared genetic and early environmental factors may contribute to the association between CD and MC.
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Enfermedad Celíaca , Colitis Colagenosa , Colitis Linfocítica , Colitis Microscópica , Humanos , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Estudios de Cohortes , Colitis Microscópica/diagnóstico , Colitis Microscópica/epidemiología , Colitis Microscópica/patología , Colitis Linfocítica/diagnóstico , Colitis Linfocítica/epidemiología , Colitis Linfocítica/patología , Colitis Colagenosa/diagnóstico , Colitis Colagenosa/epidemiología , Colitis Colagenosa/patologíaRESUMEN
BACKGROUND: Coeliac disease (CeD), a common autoimmune condition, requires strict adherence to a gluten-free diet (GFD). Adherence to the GFD has been associated with quality of life (QOL). However, there may be other diet-related concerns, such as overall diet patterns, including diet quality or ultra-processed food (UPF) consumption, possibly associated with QOL among people with CeD following a GFD that have not been examined. METHODS: Diet quality was determined based on 24-h diet recalls of a cross-sectional prospectively recruited sample of 80 participants (50 adults and 30 teens) with biopsy-confirmed CeD ('Study Sample') using the Healthy Eating Index and Alternate Mediterranean Diet score. The amount of UPF consumed was assessed using Nova, a food processing classification system. QOL was measured using Celiac Disease-Specific Quality of Life (CDQOL) and Celiac Disease Pediatric-Specific Quality of Life (CDPQOL). The Study Sample's diet patterns were compared with National Health and Nutrition Examination Survey (NHANES) groups (25 adults reporting prior CeD and GFD; 51 adults with new CeD and no GFD; 15,777 adults and 2296 teens without CeD). The relationship of the Study Sample's diet patterns with CDQOL/CDPQOL was assessed using analysis of covariance. RESULTS: The Study Sample's diet patterns were suboptimal but generally favourable compared with all NHANES groups. Compared to Study Adults with the highest tertile of UPF, those with the lowest tertile had significantly higher CDQOL (mean: 67.6 vs. 78.3, p < 0.001). Compared to Study Teens with the lowest tertile of AMED, those with the highest tertile had significantly higher CDPQOL (mean: 67.0 vs. 79.9, p < 0.01). CONCLUSIONS: Maintaining high diet quality and minimising UPF may be important for CeD-specific QOL among individuals with CeD maintaining a GFD.
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Enfermedad Celíaca , Calidad de Vida , Humanos , Adulto , Adolescente , Niño , Encuestas Nutricionales , Alimentos Procesados , Estudios Transversales , Dieta Sin GlutenRESUMEN
BACKGROUND AND OBJECTIVE: Celiac Disease (CD) is characterized by gluten intolerance in genetically predisposed individuals. High disease prevalence, absence of a cure, and low diagnosis rates make this disease a public health problem. The diagnosis of CD predominantly relies on recognizing characteristic mucosal alterations of the small intestine, such as villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. However, these changes are not entirely specific to CD and overlap with Non-Celiac Duodenitis (NCD) due to various etiologies. We investigated whether Artificial Intelligence (AI) models could assist in distinguishing normal, CD, and NCD (and unaffected individuals) based on the characteristics of small intestinal lamina propria (LP). METHODS: Our method was developed using a dataset comprising high magnification biopsy images of the duodenal LP compartment of CD patients with different clinical stages of CD, those with NCD, and individuals lacking an intestinal inflammatory disorder (controls). A pre-processing step was used to standardize and enhance the acquired images. RESULTS: For the normal controls versus CD use case, a Support Vector Machine (SVM) achieved an Accuracy (ACC) of 98.53%. For a second use case, we investigated the ability of the classification algorithm to differentiate between normal controls and NCD. In this use case, the SVM algorithm with linear kernel outperformed all the tested classifiers by achieving 98.55% ACC. CONCLUSIONS: To the best of our knowledge, this is the first study that documents automated differentiation between normal, NCD, and CD biopsy images. These findings are a stepping stone toward automated biopsy image analysis that can significantly benefit patients and healthcare providers.
Asunto(s)
Enfermedad Celíaca , Duodenitis , Enfermedades no Transmisibles , Humanos , Enfermedad Celíaca/diagnóstico , Duodenitis/diagnóstico por imagen , Duodenitis/patología , Inteligencia Artificial , Biopsia , Mucosa Intestinal/diagnóstico por imagenRESUMEN
BACKGROUND: Both undiagnosed celiac disease and some chronic childhood diseases are associated with lower academic achievement. However, there is little knowledge of achievements in those diagnosed with celiac disease. Our aim was to investigate school achievements in upper secondary school among Swedish adolescents with celiac disease. METHODS: We performed a retrospective cohort study using register data. We analyzed choice of upper secondary school program, completion of upper secondary school including achievements of basic eligibility for college/university, and final grade in individuals with celiac disease diagnosed before 15 years of age, born 1991-97. We compared with the Swedish population of the same birth years. Analyses were adjusted for sex, year of birth, living region at 17 years of age, and parental education as well as income. RESULTS: The cohort included 734 074 individuals, whereof 3 257 (62% females) with celiac disease. There was no significant difference in choice of upper secondary school program. No significant difference was found in completion or achieving basic eligibility for college/university in adjusted analyses. The mean final grade in the celiac disease group was 13.34 (standard deviation 4.85) compared to 12.78 (standard deviation 5.01) in the reference population (p < 0.001), out of a maximum of 20. The effect of celiac disease on final grade remained in adjusted analyses (p = 0.012). CONCLUSIONS: We found that diagnosed celiac disease does not negatively affect school achievements in upper secondary school. This finding suggests the diagnosis, treatment and follow-up programs of celiac disease could reverse potential deleterious academic processes.