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 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 center dot 0 years [SD 21 center dot 4]). 625 879 (63 center dot 9%) of these diagnosed individuals were female and 352 993 (36 center dot 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 center dot 04 [95% CI 1 center dot 00-1 center dot 09]). The largest increases were seen in coeliac disease (2 center dot 19 [2 center dot 05-2 center dot 35]), Sjogren's syndrome (2 center dot 09 [1 center dot 84-2 center dot 37]), and Graves' disease (2 center dot 07 [1 center dot 92-2 center dot 22]); pernicious anaemia (0 center dot 79 [0 center dot 72-0 center dot 86]) and Hashimoto's thyroiditis (0 center dot 81 [0 center dot 75-0 center dot 86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10 center dot 2% of the population over the study period (1 912 200 [13 center dot 1%] women and 668 264 [7 center dot 4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1 center dot 72 [1 center dot 64-1 center dot 81]), rheumatoid arthritis (1 center dot 52 [1 center dot 45-1 center dot 59]), Graves' disease (1 center dot 36 [1 center dot 30-1 center dot 43]), and systemic lupus erythematosus (1 center dot 35 [1 center dot 25-1 center dot 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 Sjogren'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 center dot 5 [95% CI 17 center dot 3-40 center dot 7]), coeliac disease (28 center dot 4 [25 center dot 2-32 center dot 0]), and thyroid disease (Hashimoto's thyroiditis 13 center dot 3 [11 center dot 8-14 center dot 9] and Graves' disease 6 center dot 7 [5 center dot 1-8 center dot 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.