Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK

BACKGROUND\nCoeliac disease (CD) is a disorder that may depend on genetic, immunological, and environmental factors. Recent observational studies suggest that breast feeding may prevent the development of CD.\n\n\nAIM\nTo evaluate articles that compared effects of breast feeding on risk of CD.\n\n\nMETHODS\nSystematic review and meta-analysis of observational studies published between 1966 and June 2004 that examined the association between breast feeding and the development of CD.\n\n\nRESULTS\nSix case-control studies met the inclusion criteria. With the exception of one small study, all the included studies found an association between increasing duration of breast feeding and decreased risk of developing CD. Meta-analysis showed that the risk of CD was significantly reduced in infants who were breast feeding at the time of gluten introduction (pooled odds ratio 0.48, 95% CI 0.40 to 0.59) compared with infants who were not breast feeding during this period.\n\n\nCONCLUSIONS\nBreast feeding may offer protection against the development of CD. Breast feeding during the introduction of dietary gluten, and increasing duration of breast feeding were associated with reduced risk of developing CD. It is, however, not clear from the primary studies whether breast feeding delays the onset of symptoms or provides a permanent protection against the disease. Long term prospective cohort studies are required to investigate further the relation between breast feeding and CD.

/pdf/effect-of-breast-feeding-on-risk-of-coeliac-disease-a-hr0485pcl8.pdf

Effect of breast-feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies: pg1-18

BACKGROUND
A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases.


METHODS
In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex.


FINDINGS
Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases.


INTERPRETATION
Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases.


FUNDING
Research Foundation Flanders.

Diabetic kidney disease (DKD) is a devastating condition associated with increased morbidity and premature mortality. The etiology of DKD is still largely unknown. However, the risk of DKD development and progression is most likely modulated by a combination of genetic and environmental factors. Patients with autoimmune diseases, like type 1 diabetes, inflammatory bowel disease, and celiac disease, share some genetic background. Furthermore, gastrointestinal disorders are associated with an increased risk of kidney disease, although the true mechanisms have still to be elucidated. Therefore, the principal aim of this review is to evaluate the impact of disturbances in the gastrointestinal tract on the development of renal disorders.

/pdf/the-gut-kidney-axis-putative-interconnections-between-8wmr6a17ft.pdf

The Gut-Kidney Axis: Putative Interconnections Between Gastrointestinal and Renal Disorders

Background A complex interplay between genetic and environmental factors contributes to disease etiology of most of the autoimmune disorders. Type 1 diabetes mellitus (T1DM) and celiac disease (CD) are polygenic autoimmune diseases that have high propensity to coexist due to shared etiological factors like genetics and clinico-pathological overlaps. Summary The mean prevalence rate for coexistence of these diseases is 8%, and this value is a gross underestimation as reported from biopsy-proven symptomatic cases. The prevalence rate will rise when studies will excavate bottom layers of the "celiac iceberg" to detect potential and silent celiac cases. The concomitant presence of both these disorders is a complex situation immunologically as well as clinically. There is an accentuated breakdown of tolerance and proinflammatory cytokine storm that leads to the progression of organ-specific autoimmunity to systemic. No immunomodulating drugs are advocated as exogenous insulin supplementation and gluten exclusion are recommended for T1DM and CD respectively. Nevertheless, these pose certain challenges to both the clinicians and the patients, as gluten free diet (GFD) has been described to have an impact on glycemic control, bone health, and vascular complications. Also intermittent gluten intake by these patients due to non-compliance with GFD also stimulates the autoreactive immune cells that result in an augmented immune response. Key Messages: Large public health studies are needed to estimate the prevalence of all forms of CD in T1DM patients. Strict global guidelines need to be formulated for the disease management and prognosis, and there is also a need for an extensive research on each front to thoroughly understand the co-occurrence of these diseases.

/pdf/interplay-between-type-1-diabetes-mellitus-and-celiac-4snj64dv13.pdf

Interplay between Type 1 Diabetes Mellitus and Celiac Disease: Implications in Treatment.

Type 1 diabetes (T1D) and celiac disease (CD) are autoimmune diseases with clinical and pathogenic overlap. The mean prevalence of CD in patients with T1D is about 8 %. Classic intestinal symptoms of CD may not be present in T1D leading to the recommendation for active case finding in this higher risk group. Screening is done with sensitive and specific serologies including tissue transglutaminase (tTG) IgA and deaminated gliadin peptide (DGP) IgA and IgG. Positive serologies are confirmed by the presence of villous atrophy and increased intraepithelial lymphocytes on duodenal biopsy. A strict gluten free diet is recommended, although this can pose challenges for T1D patients who already have dietary restrictions. In aggregate, it appears as if the gluten free diet may help T1D management. T1D and CD have overlapping genetic and environmental risk factors. Among these, non-HLA genetic factors and the gut microbiome are among recent developments that will be discussed in this review.

Type 1 diabetes and celiac disease: clinical overlap and new insights into disease pathogenesis.

http://www.cghjournal.org/article/S1542356523000290/pdf

Comparative Safety of Biologic Agents in Patients with Inflammatory Bowel Disease with Active or Recent Malignancy: A Multi-Center Cohort Study.

Ulcerative colitis (UC) is an idiopathic condition of the colon, in which acute and chronic inflammation results in an injured bowel. Chronic inflammatory damage, confined exclusively to the mucosa of the colorectum, is the hallmark of the disease. The inflammation is characteristically superficial in nature and appears to begin in the rectum with variable extension to more proximal portions of the colon. This inflammation, and subsequent loss of function, is the mechanism underlying the typical symptoms of UC. Although there may be more systemic symptoms, the majority of the symptoms of UC are derived from an inflamed rectum and due to loss of compliance of the rectum, loss of sensation of stool, as well as symptoms of tenesmus incomplete evacuation, urgency, and bleeding with hematochezia. The healed bowel can result in the resolution of symptoms and has been associated with disease control and resolution, but traditional clinical assessment of UC involves symptom management primarily, with the assumption that when bleeding and urgency are improved, adequate disease control has been achieved. However, resolution of bowel inflammation is not always manifest as improved or resolved symptoms, and improved symptoms are not always associated with a healed bowel or durable disease control. This chapter reviews the importance of mucosal healing as a prognostic marker and therapeutic endpoint in UC.

The Importance of Mucosal Healing in Ulcerative Colitis

Su1866 Long-Term Follow-Up of Polypoid Dysplasia and Assessment of Peri-Polyp Biopsies of Flat Mucosa in Patients With IBD-Colitis

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Papers

Type 1 diabetes and celiac disease: clinical overlap and new insights into disease pathogenesis.

Comparative Safety of Biologic Agents in Patients with Inflammatory Bowel Disease with Active or Recent Malignancy: A Multi-Center Cohort Study.

The Importance of Mucosal Healing in Ulcerative Colitis

Su1866 Long-Term Follow-Up of Polypoid Dysplasia and Assessment of Peri-Polyp Biopsies of Flat Mucosa in Patients With IBD-Colitis