Elsevier

The Lancet

Volume 401, Issue 10391, 3–9 June 2023, Pages 1878-1890
The Lancet

Articles
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

https://doi.org/10.1016/S0140-6736(23)00457-9Get rights and content

Summary

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.

Introduction

Autoimmune diseases arise when immune dysregulation causes host tissue damage.1 A wide range of autoimmune diseases are described that present with variable age of onset, tissue distribution, and clinical and functional effects.1 Most of these diseases are incurable and require lifelong treatment.

Adequate public health and service delivery planning requires reliable information about contemporary, population-level disease incidence. However, estimates of autoimmune disease incidence rates and their temporal trends, even in high-income countries, are scarce and inconsistent.1 Some autoimmune disorders, such as type 1 diabetes, are reported to have increased over the past three decades, raising the question as to whether the overall incidence of autoimmune disorders is on the rise, driven perhaps by common environmental factors or behavioural changes. Even for type 1 diabetes, the incidence of which is among the best studied within autoimmune diseases, reports rely on relatively small cohorts,2, 3 and estimates vary by a factor of ten between studies in Europe alone.4, 5 For many other autoimmune diseases, evidence concerning disease incidence and prevalence is more scarce than for diabetes. The relatively modest absolute numbers of people affected by individual autoimmune diseases is a major challenge to investigators and hinders adequate synthesis across studies.6 As a result, reliable estimates of disease incidence and how they evolve over time, particularly for autoimmune diseases as a group, are not available.

Commonalities and differences between individual diseases are also not well understood and continue to be subject to much research. Although emerging evidence has suggested that autoimmune diseases tend to co-occur within individuals, large-scale investigations across a broad spectrum of autoimmune diseases that could provide clues about shared pathogenesis and risk factors are not currently available.7, 8

To address these knowledge gaps, we analysed a large longitudinal database of primary and secondary care records in the UK that provides information on millions of individuals' diagnoses with several years of follow-up.9, 10 We aimed to investigate the incidence and prevalence for 19 of the most common autoimmune diseases, assess trends over time, by sex, age, socioeconomic status, season, and UK region, and examine rates of co-occurrence among autoimmune diseases.

Section snippets

Data source

In this population-based observational study, we used electronic health records from the GOLD and Aurum datasets of the Clinical Practice Research Datalink (CPRD) from Jan 1, 1985, to June 30, 2019. The CPRD database contains anonymised patient data from approximately 20% of the current UK population and is broadly representative in terms of age, sex, and ethnicity. CPRD is one of the largest databases of longitudinal medical records from primary care in the world and has been validated for

Results

Between Jan 1, 2000, and Dec 31, 2019, a total of 22 009 375 individuals in the CPRD database met study population criteria, with 135 691 152 patient-years of follow-up. Among these individuals, we identified 1 123 789 new diagnoses of autoimmune diseases, affecting a total of 978 872 individuals. The mean age when an autoimmune disease was diagnosed was 54·0 years (SD 21·4), and 625 879 (63·9%) of these individuals were women (table).

The number of people newly diagnosed with one (or more)

Discussion

Our large-scale, population-based study provides several novel insights into the burden of autoimmune disorders, its variation over time, and its variation by individual diseases and patient subgroups of age, sex, and socioeconomic status. Our findings support and extend evidence from previous studies showing an increasing incidence of several autoimmune disorders,20 and show that the increase was particularly pronounced for Graves' disease, coeliac disease, and rheumatic disorders. Our results

Data sharing

Access to CPRD data is conditional on a license agreement and protocol approval process that is overseen by CPRD's Independent Scientific Advisory Committee. A guide to access is provided on the CPRD website (https://cprd.com/data-access).

Declaration of interests

NC is funded by a personal fellowship from the Research Foundation Flanders (grant number 12ZU922N) and declares royalties from Oxford University Innovation. SM is funded by a Wellcome Trust Career Development Award (223024/Z/21/Z) and is supported by the NIHR Imperial Biomedical Research Centre. IBM declares honoraria from AbbVie; grant support paid to his university from AstraZeneca and Eli Lilly; participation on data safety monitoring boards or advisory boards of AstraZeneca, Bristol Myers

References (43)

  • Variation and trends in incidence of childhood diabetes in Europe

    Lancet

    (2000)
  • DSA McLeod et al.

    The incidence and prevalence of thyroid autoimmunity

    Endocrine

    (2012)
  • EC Somers et al.

    Autoimmune diseases co-occurring within individuals and within families: a systematic review

    Epidemiology

    (2006)
  • EC Somers et al.

    Are individuals with an autoimmune disease at higher risk of a second autoimmune disorder?

    Am J Epidemiol

    (2009)
  • E Herrett et al.

    Data resource profile: Clinical Practice Research Datalink (CPRD)

    Int J Epidemiol

    (2015)
  • A Wolf et al.

    Data resource profile: Clinical Practice Research Datalink (CPRD) Aurum

    International Journal of Epidemiology

    (2019)
  • LE Dean et al.

    Global prevalence of ankylosing spondylitis

    Rheumatology (Oxford)

    (2014)
  • J Chisholm

    The Read clinical classification

    BMJ

    (1990)
  • SNOMED CT

  • The English Index of Multiple Deprivation 2015: guidance

  • B Kirkwood et al.

    Essential medical statistics

    (2010)
  • Cited by (0)

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    Justin Mason died in May, 2022

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