The International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) is a global health coding system that provides a standardised language for recording, reporting and monitoring diseases. However, epidemiological studies using real-world data on clinically diagnosed coeliac disease (CD) based on the ICD-10-CM remain limited.

To evaluate in primary care: (1) the diagnostic adequacy of CD; (2) the accuracy of the ICD-10-CM code K90.0 for identifying CD; and (3) the prevalence of clinically diagnosed CD compared with the known CD seroprevalence in the same geographical area (5‰).

This was a population-based, cross-sectional study in the city of L'Hospitalet de Llobregat (269,382 inhabitants), Catalonia, from 2005 to 2020. The data retrieved with the K90.0 code from electronic medical records were cross-checked against laboratory and pathology registries. The CD diagnostic criteria were validated on a case-by-case basis. To calculate the accuracy of the K90.0 code for identifying CD, patients were classified into confirmed versus uncertain/misdiagnosed CD.

Overall, 536/737 patients (73 %) had confirmed CD, and 201/737 (27 %) were misdiagnosed. The accuracy of the K90.0 code for identifying CD was as follows: sensitivity, 91.63 %; specificity, 99.95 %; positive predictive value, 63.85 %; and negative predictive value, 99.99 %. The prevalence of clinically diagnosed CD was 1.99‰, with a decreasing age-related trend of -7.5 %.

The ICD-10-CM code K90.0 is accurate for identifying clinically diagnosed CD and is thus a great tool for epidemiological disease surveillance. The gap between CD seroprevalence and the prevalence of clinically diagnosed CD (5‰ vs. 1.99‰) calls for the implementation of case-finding programmes to reduce underdiagnosis.

As it appears that we are currently at the cusp of an era in which drugs that are new, re-purposed, or "supplements" will be introduced to the management of celiac disease, we need to reflect on whether the framework is set for celiac disease to be treated increasingly with pharmaceuticals as well as diet. This refers to reflecting on the rigor of current diagnostic practices; the limitations of the current standard of care, which is a gluten-free diet; and that we lack objective markers of disease severity. Investigating these issues will help us to identify gaps in technology and practices that could be critical for selecting patients with a well-defined need for an improved or alternative treatment. Both aspects, circumscribed limitations of the gluten-free diet and diagnostics helping to define celiac disease target groups, together with the guiding requirements by the responsible regulatory authorities, will contribute to defining the subgroups of patients with confirmed celiac disease eligible for distinct pharmacologic strategies. Because many patients with celiac disease are diagnosed in childhood, these aspects need to be differentially discussed for the pediatric setting. In this perspective, we aimed to describe these contextual issues and then looked ahead to the future. What might be the major challenges in celiac disease clinics in the coming years once drugs are an option alongside diet? And what will be the future objectives for researchers who further decipher the mucosal immunology of celiac disease? Speculating on the answers to these questions is as stimulating as it is fascinating to be part of this turning point.

The assessment of the nutritional and inflammatory status of paediatric patients with coeliac disease is an interesting approach to early diagnosis and functional follow-up. Most authors agree that the normalisation of symptoms takes about one year. The aim of the study was to evaluate the clinical manifestation and normalisation of routine analytics in Spanish children diagnosed with celiac disease.

We performed a retrospective case-control study in Spanish paediatric patients, including 21 celiac patients and 20 healthy controls. The 21 patients selected in the case-control study were followed for 5 years after starting a gluten-free diet (GFD). All patients had type 3 villous atrophy according to the Marsh-Oberhuber classification. A total of 39 blood samples were taken before the start of the GFD, and 109 were taken after. Twenty control sera from healthy donors were used for comparison.

We found that patients had a subclinical but statistically significant increase in blood calcium, transaminases, and white blood cells, and a decrease in serum iron, at the time of diagnosis. Our study also shows that analytical values normalise within five years on a gluten-free diet.

The use of a combination of subclinical changes, including low iron, high calcium, elevated leukocytes, lymphocytes, and ALT levels in blood samples, together with a low growth percentile, is pertinent in detecting coeliac disease. This set of parameters could help in the diagnosis of patients without clinical symptoms. We can also show that the levels of Fe, Ca, transaminases, and leucocytes remain subclinically altered after 3 years, despite the gluten-free diet.

Coeliac disease is a systemic disorder characterized by immune-mediated enteropathy, which is caused by gluten ingestion in genetically susceptible individuals. The clinical presentation of coeliac disease is highly variable and ranges from malabsorption through solely extra-intestinal manifestations to asymptomatic. As a result, the majority of patients with coeliac disease remain undiagnosed, misdiagnosed or experience a substantial delay in diagnosis. Coeliac disease is diagnosed by a combination of serological findings of disease-related antibodies and histological evidence of villous abnormalities in duodenal biopsy samples. However, variability in histological grading and in the diagnostic performance of some commercially available serological tests remains unacceptably high and confirmatory assays are not readily available in many parts of the world. Currently, the only effective treatment for coeliac disease is a lifelong, strict, gluten-free diet. However, many barriers impede patients' adherence to this diet, including lack of widespread availability, high cost, cross-contamination and its overall restrictive nature. Routine follow-up is necessary to ensure adherence to a gluten-free diet but considerable variation is evident in follow-up protocols and the optimal disease management strategy is not clear. However, these challenges in the diagnosis and management of coeliac disease suggest opportunities for future research.

Wheat and other gluten-containing grains are widely consumed, providing approximately 50% of the caloric intake in both industrialised and developing countries. The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence. This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media. However, in recent years, the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease (CD) from obscurity to global prominence. These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD. Different scientific societies, mainly from Europe and America, have proposed guidelines based on CD's most recent evidence.

To identify the most recent scientific guidelines on CD, aiming to find and critically analyse the main differences.

We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language. PubMed was lastly accessed on 1 March 2021.

We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions. Differences were noted in the possibility of a no-biopsy diagnosis, HLA testing, follow-up protocols, and procedures.

We found a relatively high concordance between the guidelines for CD. Important modifications have occurred in the last years, especially about the possibility of a no-biopsy diagnosis in children. Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities.

Background and objectives: Duodenal lymphocytosis (DL) is a condition characterized by enhanced infiltration of intraepithelial lymphocytes (IELs) in the duodenal mucosa, and it can be linked to both gluten- and non-gluten-related diseases, such as irritable bowel syndrome (IBS). Materials and methods: We retrospectively selected patients with DL linked to IBS. Formalin-embedded biopsy samples of the duodenum were collected. CD3 lymphocyte immunohistochemistry was used for IELs. The real-time polymerase chain reaction was used to quantify the amount of mRNA coding for tissue transglutaminase 2 (tTG2), interferon-gamma (IFNγ), toll-like receptor 2 (TLR2), and myeloid differentiation primary response 88 (MyD88). All subjects underwent DQ2-8 haplotype analysis. Controls were represented by subjects with IBS without DL. Results: Thirty-two patients with IBS-DL were retrospectively recruited. Fourteen subjects (43.8%) had a DQ2-8 haplotype. DQ2-8 positive subjects had similar levels compared to negative ones for tTG2, IFNγ, TLR2, and MyD88. Cigarette smoke did not influence molecular expression in our study. Smokers had a statistically higher IELs count than non-smokers (54.2 ± 7.7 vs. 36.0 ± 8.8, p < 0.001). A significant, direct correlation between IELs and duodenal expression of IFNγ was found (r = 0.36, p = 0.04). Conclusions: IBS with DL showed higher expression of inflammatory markers than controls, but DQ2-8 haplotype did not seem to affect their expression. Smoking might increase IELs infiltration.

Celiac disease (CeD) is a lifelong immune-mediated enteropathy in which dietary gluten triggers an inflammatory reaction in the small intestine. This retrospective cohort study examines healthcare resource utilization (HRU) and costs between patients with CeD and matched controls.

Patients with CeD (cases) with an endoscopic biopsy and ≥2 medical encounters with a CeD diagnosis between January 1, 2010, and October 1, 2015, were identified in the MarketScan databases. The date of the first claim with a CeD diagnosis on or after the endoscopic biopsy was the index date. Cases were matched 1:1 to patients without CeD (controls) on demographic characteristics and Deyo-Charlson Comorbidity Index score. Clinical characteristics, all-cause, and CeD-related HRU and costs (adjusted to 2017 US dollars) were compared between cases and controls during the 12 months before (baseline) and 24 months after (follow-up) the index date.

A total of 11,008 cases (mean age 40.6 years, 71.3% women) were matched to 11,008 controls. During the follow-up, a higher proportion of cases had all-cause and CeD-related HRU including inpatient admissions, emergency department visits, gastroenterologist visits, dietician visits, endoscopic biopsies, and gastroenterology imaging (all P ≤ 0.002). Incremental all-cause and CeD-related costs were in the first ($7,921 and $2,894) and second ($3,777 and $935) year of follow-up, driven by outpatient services costs.

In this US national claims database analysis, there was evidence of an increase in both all-cause and CeD-related HRU and related costs in patients with CeD compared with matched patients without CeD, suggesting a significant economic burden associated with CeD.

Gluten-free (GF) foods are typically less nutritious and more expensive than their gluten-containing variants, yet people without a diagnosed gluten sensitivity continue to adopt this diet. There is a lack of research about what factors drive people without Celiac disease or non-Celiac gluten sensitivity to follow the GF diet.

A nationally representative sample of 2982 US residents without a diagnosed gluten sensitivity were surveyed about their attitudes, perceptions, and experiences with the GF diet. Logistic regression was used to compare respondents who were currently avoiding or had avoided gluten previously (GF consumer) to respondents who had never tried a GF diet (non-GF consumer).

Over one-fifth of respondents were GF consumers. Beliefs that a gluten-reduced diet is healthier (OR 1.69; 95% CI [1.30,2.18]), that GF products are more nutritious (OR 1.46, 95% CI [1.11,1.90), and that a GF diet can help clear acne (OR 1.46; 95% CI [1.13,1.88]) were all positively associated with trying a GF diet. Personal research was the most influential source of information associated with trying a GF diet (OR 2.92; 95% CI [1.91,4.52]). This was followed by "healthcare center or health professional" (OR 2.57; 95% CI [1.71,3.90]. Respondents who were never encouraged to try the GF diet were less likely to try the diet (OR 0.33, 95% CI [0.23,0.46]).

Positive, but scientifically unsubstantiated, beliefs about the benefits of the GF diet were strongly associated with trying a GF diet, and the source of recommendation to try a GF diet was important.

The association between autoimmune atrophic gastritis and thyroid disorders has been observed since the early 1960s and the expression "thyrogastric syndrome" was coined to indicate the presence of thyroid autoantibodies or autoimmune thyroid disease in patients with pernicious anemia, a late clinical stage of autoimmune atrophic gastritis. More recently, it was confirmed that autoimmune thyroid disorders, in particular Hashimoto's thyroiditis, may be frequently associated with other organ-specific, immune-mediated disorders, such as autoimmune atrophic gastritis or celiac disease. The association of Hashimoto's thyroiditis with autoimmune atrophic gastritis or celiac disease in adult patients is currently considered part of the polyglandular autoimmune syndromes which include several autoimmune disorders associated with an autoaggressive impairment of endocrine glands. From a clinical point of view, the thyro-entero-gastric autoimmunity may lead to potentially serious consequences like anemia, micronutrients deficiencies, and drugs malabsorption, as well as to an increased risk for malignancies. These alterations may frequently present in an underhand manner, with consequent diagnostic and treatment delays. Many aspects of the association between thyroid, gastric and intestinal autoimmune diseases still await clarification. The present review focuses on the embryological, genetic and pathophysiological aspects of thyro-entero-gastric autoimmunity. In particular, the current diagnostic criteria of autoimmune thyroid disease, autoimmune atrophic gastritis, and celiac disease are reviewed, along with the evidences for their association in poly-autoimmunity syndromes. The benefits of proactive screening of autoimmune thyroid disorders in patients with autoimmune gastritis or enteropathy and viceversa are also discussed.

Celiac disease (CD) is an immune-mediated gastrointestinal (GI) disorder driven by innate and adaptive immune responses to gluten. Presentation of CD has changed over time, with non-GI symptoms, such as anemia and osteoporosis, presenting more commonly. With improved screening and diagnostic methods, the reported prevalence of CD has increased globally, and there is considerable global variation in diagnostic and treatment practices. The objective of this study was to describe the current state of CD diagnosis and treatment patterns. A targeted review of literature from MEDLINE, Embase, the Cochrane Library, and screening of relevant conference abstracts was performed. The generally recommended diagnostic approach is GI endoscopy with small bowel biopsy; however, in selected patients, biopsy may be avoided and diagnosis based on positive serology and clinical symptoms. Diagnosis often is delayed; the average diagnostic delay after symptom onset is highly variable and can last up to 12 years. Barriers to accurate and timely diagnosis include atypical presentation, lack of physician awareness about current diagnostic criteria, misdiagnosis, and limited access to specialists. Currently, strict adherence to a gluten-free diet (GFD) is the only recommended treatment, which is not successful in all patients. Only one-third of patients are monitored regularly following diagnosis. Unmet needs for CD include improvements in the accuracy and timeliness of diagnosis, and the development of treatments for both refractory CD and GFD nonresponsive CD. Further research should investigate the impact of education about gluten-free eating and the availability of gluten-free foods support adherence and improve outcomes in patients with CD.

Accurate and prompt diagnosis of celiac disease has proven difficult due to the myriad of presenting symptoms and a lack of a clear diagnostic protocol. This pilot study investigated the use of an evidence-based multimedia educational module on nurse practitioner confidence and knowledge of celiac disease. Thirteen nurse practitioners in Pennsylvania completed all study activities, which involved the use of an online pretest, learning component, an immediate post-test, along with 2 follow-up surveys. Results revealed that nurse practitioner confidence (p ≤ .05) and knowledge (p ≤ .05) levels significantly improved after participation in the educational intervention. Qualitative data also revealed that nurse practitioners are more aware of the various presentations and symptoms of celiac disease and stated that with this knowledge, their clinical practice has changed to include recognition of the various celiac disease presentations. Findings suggest that nurse practitioners are now more knowledgeable of the various presentations of celiac disease and may be more likely to consider celiac disease as a diagnosis if patients present with typical or atypical symptoms.

Non-celiac gluten sensitivity (NCGS) is an emerging gluten-related condition. We investigated whether the presence of autoimmune stigmata in a group of patients with clinical suspicion of NCGS and a histological picture of microscopic enteritis (ME) could be a predictive factor of NCGS. Patients with ME were followed up by periodical examinations. At baseline, we collected data about previous clinical history, including autoimmune diseases. NCGS was diagnosed according to Salerno criteria; other causes of ME were diagnosed according to well-established protocols. Patients with celiac disease were excluded. Student's and chi-square tests were used in univariate analysis. Kaplan-Meier curves and Cox regression were used to estimate hazard ratios (HR). Sixty-three patients were included. Twenty-two had a final diagnosis of NCGS; the remaining 41 had non-gluten-related causes of ME. Prevalence of autoimmune thyroiditis was higher among NCGS patients (40.1%) than in other ME (14.6%; p = 0.03). NCGS showed higher positivity rate for anti-gliadin (27.3% versus 2.5%; p = 0.006) and anti-nucleus (45.4% versus 12.2%; p = 0.005). Autoimmune thyroiditis had a non-significant trend (p = 0.06) for NCGS diagnosis, (HR = 2.4). Both anti-gliadin (HR = 2.4; p = 0.04) and anti-nucleus (HR = 2.7; p = 0.04) were directly associated with NCGS diagnosis. In conclusion, NCGS may have a cohort of autoimmune stigmata that can precede its diagnosis.

This study aimed to investigate follow-up patterns among celiac disease (CD) patients.

Gender factors are important in CD with women diagnosed more frequently than men despite equal seropositivity in screening studies. To determine if gender influences postdiagnosis care, we performed a retrospective cohort study investigating the impact of gender and mode of presentation on follow-up patterns after diagnosis.

The study included adults with biopsy-proven CD presenting to a single tertiary care center between 2005 and 2014. The primary exposure was at least 1 visit with a CD specialist. The primary outcome was ≥2 follow-up visits, including office visits and endoscopic procedures. Data extracted included whether patients had tissue transglutaminase antibodies performed by our laboratory.

We analyzed 708 patients of which 70.5% were female. Follow-up was good with a majority of patients (69%) having at least 1 follow-up visit. On bivariate analysis, patients least likely to follow-up were ages 18 to 29 (P=0.03) and women with atypical presentations (P=0.003). After adjusting for potential confounders, individuals over age 65 were significantly more likely to attend at least 2 follow-up visits (odds ratio, 2.07; 95% confidence interval, 1.21-3.55; P=0.0079). Individuals with an abnormal baseline tissue transglutaminase antibody value in our laboratory were significantly more likely to follow-up (odds ratio, 1.99; 95% confidence interval, 1.39-2.85; P=0.0002).

Gender had no impact on follow-up patterns despite prior studies demonstrating an impact on diagnosis rates. Future attention should focus on retaining young patients and those with atypical modes of presentation.

Coeliac disease (CD) is an autoimmune disorder of the small bowel associated with increased risk of additional autoimmune diseases (ADs).To investigate the prevalence of ADs in a population of adult coeliac patients.This was a retrospective case-control study. Data from coeliac patients and controls referred to a tertiary center between 2013 and 2016 were collected. The frequency of ADs and the unadjusted and adjusted odds ratios (ORs) for age, gender, disease duration, and body mass index with their 95% confidence intervals (CIs) were evaluated.Two hundred fifty-five patients with CD (median age 37.1 years; 206 women) were matched with 250 controls. ADs were more frequent (35.3%) in coeliac patients than in controls (15.2%). Adjusted ORs for the presence of only 1, at least 1, and more than 1 AD were 3.13 (95% CI 1.81-5.42, P < .0001), 3.31 (95% CI 2.00-5.46, P < .0001), and 3.93 (95% CI 1.49-10.36, P = .006), respectively. Hashimoto thyroiditis was the most prevalent AD (24.3% vs. 10%) OR = 2.55 (95% CI 1.39-4.70, P < .0001), followed by psoriasis (4.3% vs. 1.6%), type 1 diabetes (2.7% vs. 0.4%), and Sjögren syndrome (2.4% vs. 0.4%).These findings suggest a need for a careful surveillance of autoimmune status, especially for Hashimoto thyroiditis in patients with celiac disease.

Macrophage activation syndrome is described as a "clinical syndrome of hyperinflammation resulting in an uncontrolled and ineffective immune response" in the context of an autoinflammatory or rheumatic disease. Current associations of macrophage activation syndrome with autoimmune disease most notably include a host of rheumatological conditions and inflammatory bowel disease. Epidemiological studies have shown that macrophage activation syndrome is precipitated by autoimmune disease more commonly than previously thought. Diagnosing the precipitating factor is essential for effective treatment and prognosis.

We report a case of a six year old girl with coeliac disease diagnosed after two episodes of secondary haemophagocytic lymphohistiocytosis. Her condition only responded to treatment once the patient was placed on a gluten free diet. Further immunological testing confirmed anti-transglutaminase and anti-endomysial antibodies, however histological biopsy was deemed inappropriate due to the severity of her condition. She has remained stable with no further episodes of macrophage activation syndrome since commencing a gluten free diet.

This case report is the first literature that links macrophage activation syndrome to coeliac disease and highlights the challenge of diagnosing coeliac disease with unusual features such as associated prolonged fever. Clinicians should have a low threshold for screening children with other autoimmune diseases for coeliac disease.