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Cited by 884Systemic Lupus Erythematosus ResearchChronic Disease Management StrategiesRheumatoid Arthritis Research and Therapies

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

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Conrad, Nathalie, Misra, Shivani, Verbakel, Jan Y, Verbeke, Geert, Molenberghs, Geert, Taylor, Peter N, Mason, Justin, Sattar, Naveed +4 more·2023·The Lancet
DOI 10.1016/s0140-6736(23)00457-9
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Abstract

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.

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  • The incidence of Hashimoto's thyroiditis has been steadily increasing, although the cause is incompletely understood.

    “The incidence of Hashimoto's thyroiditis has been steadily increasing, 26 although the cause is incompletely understood.”

    From Hypothyroidism (2024) · cites this paper as [26]

    The Temporal trends section reports that Hashimoto’s thyroiditis declined modestly over the study period, contrary to the cited claim that its incidence has been steadily increasing. The Discussion likewise describes a reduction over time and offers a possible explanation for it. (LLM, conf=0.93)

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  • At the individual level, hypothyroidism is more common in patients with other autoimmune diseases than in the general population, including rheumatoid arthritis, type 1 diabetes, Addison's disease, and coeliac disease.

    “At the individual level, hypothyroidism is more common in patients with other autoimmune diseases than in the general population, including rheumatoid arthritis, type 1 diabetes, Addison's disease, and coeliac disease, 26”

    From Hypothyroidism (2024) · cites this paper as [26]

    The Co-occurrence of autoimmune diseases section (page unavailable) reports significantly higher rates of thyroid diseases in patients with type 1 diabetes, and the Added value section identifies an association between coeliac and thyroid diseases. The cited passages do not establish that hypothyroidism specifically is more common in patients with rheumatoid arthritis or Addison's disease than in the general population; they often discuss thyroid diseases more broadly. (LLM, conf=0.84)

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Authors
Conrad, N., Misra, S., Verbakel, J. Y., Verbeke, G., Molenberghs, G., Taylor, P. N., Mason, J., Sattar, N., McMurray, J. J. V., McInnes, I. B., Khunti, K., & Cambridge, G.
Affiliations
  • University of Oxford (GB)
  • Imperial College London (GB)
  • Hasselt University (BE)
  • Cardiff University (GB)
  • University of Glasgow (GB)
  • University of Leicester (GB)
  • University College London (GB)
Corresponding author
Conrad, Nathalie
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2023-06
Volume
401
Issue
10391
Pages
1878-1890
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(23)00457-9
OpenAlex
W4372214968
Cited by
879
References
40
Citations by year
2026: 245 · 2025: 323 · 2024: 258 · 2023: 53
FWCI
185.51
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • Document Server@UHasselt (UHasselt) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Lirias (submittedVersion, other-oa)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by-nc-nd)
Funders
  • Research Foundation Flanders
  • Center for Participatory Research and Development
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Epidemiology › Chronic Disease Management Strategies
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Keywords
autoimmune disease, incidence, prevalence, temporal trends, comorbidities, socioeconomic status, sex differences, age differences, seasonal variation, regional variation, celiac disease, Sjögren's syndrome, multiple sclerosis, rheumatoid arthritis, psoriasis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, vitiligo, psoriatic arthritis
MeSH terms
Anemia, Pernicious, Autoimmune Diseases, Celiac Disease, Child, Diabetes Mellitus, Type 1, England, Female, Graves Disease, Humans, Lupus Erythematosus, Systemic, Male, Middle Aged, Sjogren's Syndrome, Social Class, Thyroiditis, Cohort Studies, Incidence, Prevalence

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