Spondyloarthritis (SpA) is a group of chronic inflammatory diseases affecting the spine and peripheral joints, causing pain, stiffness, and reduced mobility. This narrative review examines how lifestyle factors-specifically smoking, alcohol consumption, and unhealthy diet-contribute to the onset and progression of SpA. It highlights their impact on disease activity, comorbidities, radiographic damage, and treatment response. Therefore, healthcare providers are encouraged to support patients in making personalized lifestyle changes. These findings underscore the importance of a comprehensive approach to SpA management, integrating lifestyle modifications with conventional therapies for optimal disease control and improved outcomes.

Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to have a diagnosis. Untreated coeliac disease may lead to malnutrition, anaemia, osteoporosis and lymphoma.

The objectives were to define at-risk groups and determine the cost-effectiveness of active case-finding strategies in primary care.

(1) Systematic review of the accuracy of potential diagnostic indicators for coeliac disease. (2) Routine data analysis to develop prediction models for identification of people who may benefit from testing for coeliac disease. (3) Systematic review of the accuracy of diagnostic tests for coeliac disease. (4) Systematic review of the accuracy of genetic tests for coeliac disease (literature search conducted in April 2021). (5) Online survey to identify diagnostic thresholds for testing, starting treatment and referral for biopsy. (6) Economic modelling to identify the cost-effectiveness of different active case-finding strategies, informed by the findings from previous objectives.

For the first systematic review, the following databases were searched from 1997 to April 2021: MEDLINE® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), Cochrane Library, Web of Science™ (Clarivate™, Philadelphia, PA, USA), the World Health Organization International Clinical Trials Registry Platform ( WHO ICTRP ) and the National Institutes of Health Clinical Trials database. For the second systematic review, the following databases were searched from January 1990 to August 2020: MEDLINE, Embase, Cochrane Library, Web of Science, Kleijnen Systematic Reviews ( KSR ) Evidence, WHO ICTRP and the National Institutes of Health Clinical Trials database. For prediction model development, Clinical Practice Research Datalink GOLD, Clinical Practice Research Datalink Aurum and a subcohort of the Avon Longitudinal Study of Parents and Children were used; for estimates for the economic models, Clinical Practice Research Datalink Aurum was used.

For review 1, cohort and case-control studies reporting on a diagnostic indicator in a population with and a population without coeliac disease were eligible. For review 2, diagnostic cohort studies including patients presenting with coeliac disease symptoms who were tested with serological tests for coeliac disease and underwent a duodenal biopsy as reference standard were eligible. In both reviews, risk of bias was assessed using the quality assessment of diagnostic accuracy studies 2 tool. Bivariate random-effects meta-analyses were fitted, in which binomial likelihoods for the numbers of true positives and true negatives were assumed.

People with dermatitis herpetiformis, a family history of coeliac disease, migraine, anaemia, type 1 diabetes, osteoporosis or chronic liver disease are 1.5-2 times more likely than the general population to have coeliac disease; individual gastrointestinal symptoms were not useful for identifying coeliac disease. For children, women and men, prediction models included 24, 24 and 21 indicators of coeliac disease, respectively. The models showed good discrimination between patients with and patients without coeliac disease, but performed less well when externally validated. Serological tests were found to have good diagnostic accuracy for coeliac disease. Immunoglobulin A tissue transglutaminase had the highest sensitivity and endomysial antibody the highest specificity. There was little improvement when tests were used in combination. Survey respondents (n = 472) wanted to be 66% certain of the diagnosis from a blood test before starting a gluten-free diet if symptomatic, and 90% certain if asymptomatic. Cost-effectiveness analyses found that, among adults, and using serological testing alone, immunoglobulin A tissue transglutaminase was most cost-effective at a 1% pre-test probability (equivalent to population screening). Strategies using immunoglobulin A endomysial antibody plus human leucocyte antigen or human leucocyte antigen plus immunoglobulin A tissue transglutaminase with any pre-test probability had similar cost-effectiveness results, which were also similar to the cost-effectiveness results of immunoglobulin A tissue transglutaminase at a 1% pre-test probability. The most practical alternative for implementation within the NHS is likely to be a combination of human leucocyte antigen and immunoglobulin A tissue transglutaminase testing among those with a pre-test probability above 1.5%. Among children, the most cost-effective strategy was a 10% pre-test probability with human leucocyte antigen plus immunoglobulin A tissue transglutaminase, but there was uncertainty around the most cost-effective pre-test probability. There was substantial uncertainty in economic model results, which means that there would be great value in conducting further research.

The interpretation of meta-analyses was limited by the substantial heterogeneity between the included studies, and most included studies were judged to be at high risk of bias. The main limitations of the prediction models were that we were restricted to diagnostic indicators that were recorded by general practitioners and that, because coeliac disease is underdiagnosed, it is also under-reported in health-care data. The cost-effectiveness model is a simplification of coeliac disease and modelled an average cohort rather than individuals. Evidence was weak on the probability of routine coeliac disease diagnosis, the accuracy of serological and genetic tests and the utility of a gluten-free diet.

Population screening with immunoglobulin A tissue transglutaminase (1% pre-test probability) and of immunoglobulin A endomysial antibody followed by human leucocyte antigen testing or human leucocyte antigen testing followed by immunoglobulin A tissue transglutaminase with any pre-test probability appear to have similar cost-effectiveness results. As decisions to implement population screening cannot be made based on our economic analysis alone, and given the practical challenges of identifying patients with higher pre-test probabilities, we recommend that human leucocyte antigen combined with immunoglobulin A tissue transglutaminase testing should be considered for adults with at least a 1.5% pre-test probability of coeliac disease, equivalent to having at least one predictor. A more targeted strategy of 10% pre-test probability is recommended for children (e.g. children with anaemia).

Future work should consider whether or not population-based screening for coeliac disease could meet the UK National Screening Committee criteria and whether or not it necessitates a long-term randomised controlled trial of screening strategies. Large prospective cohort studies in which all participants receive accurate tests for coeliac disease are needed.

This study is registered as PROSPERO CRD42019115506 and CRD42020170766.

This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 44. See the NIHR Journals Library website for further project information.

Nonceliac wheat sensitivity (NCWS) is characterized by intestinal and extraintestinal manifestations consequent to wheat ingestion in subjects without celiac disease and wheat allergy. Few studies investigated the relationship between NCWS and autoimmunity. The aim of this study is to evaluate the frequency of autoimmune diseases (ADs) and autoantibodies in patients with NCWS.

Ninety-one patients (13 men and 78 women; mean age of 40.9 years) with NCWS, recruited in a single center, were included. Seventy-six healthy blood donors (HBD) and 55 patients with a diagnosis of irritable bowel syndrome (IBS) unrelated to NCWS served as controls. Autoantibodies levels were measured. Human leukocyte antigen haplotypes were determined, and duodenal histology performed in all patients carrying the DQ2/DQ8 haplotypes. Participants completed a questionnaire, and their medical records were reviewed to identify those with ADs.

Twenty-three patients with NCWS (25.3%) presented with ADs; autoimmune thyroiditis (16 patients, 17.6%) was the most frequent. The frequency of ADs was higher in patients with NCWS than in HBD (P = 0.002) and in patients with IBS (P = 0.05). In the NCWS group, antinuclear antibodies tested positive in 71.4% vs HBD 19.7%, and vs patients with IBS 21.8% (P < 0.0001 for both). The frequency of extractable nuclear antigen antibody (ENA) positivity was significantly higher in patients with NCWS (21.9%) than in HBD (0%) and patients with IBS (3.6%) (P = 0.0001 and P = 0.004, respectively). Among the patients with NCWS, 9.9% tested positive for antithyroglobulin, 16.5% for antithyroid peroxidase, and 14.3% for antiparietal cell antibodies; frequencies were not statistically different from controls. The presence of ADs was related to older age at NCWS diagnosis, female sex, duodenal lymphocytosis, and eosinophil infiltration.

One in 4 patients with NCWS suffered from AD, and serum antinuclear antibodies were positive in a very high percentage of cases. These data led us to consider NCWS to be associated to ADs.

We aim to review the current literature on the association of musculoskeletal disorders and celiac disease that is a common disorder, affecting about 1% of the population. Extra-intestinal symptoms and presentations predominate.

While the literature supports an association with reduced bone mineral density and increased fracture risk and celiac disease, there is little evidence supporting associations with other rheumatological conditions. Patients frequently report musculoskeletal symptoms; however, studies of specific disease entities suffer from a lack of standardization of testing for celiac disease and a lack of control groups. Well-controlled, preferably population-based studies are required to further explore a relationship between celiac disease and musculoskeletal disorders.

Celiac disease is an autoimmune systemic disease having among its clinical manifestations frequent symptoms common to rheumatologic diseases such as musculoskeletal pain, asthenia, and cognitive fatigue. It is associated with other autoimmune diseases like Sjögren disease. It is a well-characterized disease with specific diagnostic tests. Non-celiac gluten sensitivity is an emerging entity with symptoms similar to celiac disease, but without specific diagnostic tests. The concept of non-celiac gluten sensitivity and its diagnostic problems are reviewed, and the hypothesis of its association with fibromyalgia, spondyloarthritis, and autoimmune conditions is proposed. Clinical observations supporting the hypothesis are described, highlighting the benefit of treating non-celiac gluten sensitivity.

Celiac disease (CD) is a unique autoimmune disorder in which the genetic factors (DQ2/DQ8) and the environmental trigger (gluten) are known and necessary but not sufficient for its development. Other environmental components contributing to CD are poorly understood. Studies suggest that aspects of gluten intake might influence the risk of CD occurrence and timing of its onset, i.e., the amount and quality of ingested gluten, together with the pattern of infant feeding and the age at which gluten is introduced in the diet. In this study, we hypothesize that the intestinal microbiota as a whole rather than specific infections dictates the switch from tolerance to immune response in genetically susceptible individuals. Using a sample of infants genetically at risk of CD, we characterized the longitudinal changes in the microbial communities that colonize infants from birth to 24 months and the impact of two patterns of gluten introduction (early vs. late) on the gut microbiota and metabolome, and the switch from gluten tolerance to immune response, including onset of CD autoimmunity. We show that infants genetically susceptible to CD who are exposed to gluten early mount an immune response against gluten and develop CD autoimmunity more frequently than at-risk infants in which gluten exposure is delayed until 12 months of age. The data, while derived from a relatively small number of subjects, suggest differences between the developing microbiota of infants with genetic predisposition for CD and the microbiota from infants with a non-selected genetic background, with an overall lack of bacteria of the phylum Bacteriodetes along with a high abundance of Firmicutes and microbiota that do not resemble that of adults even at 2 years of age. Furthermore, metabolomics analysis reveals potential biomarkers for the prediction of CD. This study constitutes a definite proof-of-principle that these combined genomic and metabolomic approaches will be key to deciphering the role of the gut microbiota on CD onset.

Several studies have indicated that adult patients with spondyloarthritis (SpA) have elevated levels of antibodies associated with celiac disease (CD). This has not been studied in children, and none of the studies corrected for total IgA levels.

We measured total IgA and IgA against tissue transglutaminase (TTG) levels in 42 children with Juvenile Idiopathic Arthritis (JIA), of whom 11 had SpA, along with 10 non-inflammatory control subjects.

Median (IQR) TTG IgA levels were elevated among children with ERA (8.8, 4.6 - 21) compared to 'JIA controls' (JIA subgroups other than ERA) (2.8, 1.5 - 5.9) and a healthy non-inflammatory control group (1.5, 0.82 - 12), p = 0.017, Kruskal-Wallis. There was no correlation between TTG IgA levels and measures of disease activity or with medicine use. None of the children were diagnosed endoscopically with celiac disease. Patients with ERA likewise had elevated total IgA level compared to the other groups (p = 0.001), and total IgA levels correlated highly with TTG IgA (r = 0.599, p<0.001).

These findings suggest that elevations in TTG IgA may reflect increased polyclonal IgA production, rather than a specific intestinal inflammatory process.

Spondyloarthritis (SpA) are diseases with increased gut inflammation. To search for (anti-Saccharomyces cerevisiae) ASCA IgA, ASCA IgG, and anti-endomysial antibodies (EmA-IgA) in a cohort of 70 patients with SpA, we found 18.6% (13/70) positive for IgA-ASCA in the SpA group and 3/57 (5.2%) in the control group (P = 0.031). ASCA IgG and EmA-IgA were found at the same frequency in SpA and controls. No relationship of ASCA IgA positivity could be established with disease activity (measured by ESR, C-reactive protein, and BASDAI), presence of uveitis, or peripheral arthritis neither with functional status measured by BASFI. SpA patients present an increase in the IgA-ASCA positivity without any relationship to disease activity, functional index, clinical profile or the presence of HLA-B27. There is no evidence of higher prevalence of EmA-IgA in SpA patients in the studied sample.

Inflammatory arthritis presents in a variety of diseases, from rheumatoid arthritis to hepatitis. Antibodies to autoantigens or to microbial constituents are commonly associated with these conditions. In some cases, the antibodies have diagnostic and prognostic relevance. It cannot as yet be determined definitively that any of them mediate joint damage, although the evidence from animal models indicates that this mechanism is likely. The purpose of this article is to give an overview of the spectrum of antibodies found in a variety of inflammatory arthritides. The relevant animal models are also discussed.