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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
Open accessAbstract
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, 26 although the cause is incompletely understood.”
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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, 26”
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Zhao, X., Wang, N., Wang, J., Wu, F., Zhao, S., Jiang, S., Fan, X., Sun, M., Song, R., Lan, T., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3796496/v1 · Cited by 1
Nasir, N., & Mak, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-99967-0.00178-2 · Cited by 1
Liu, Y., Huang, C., Lin, R., Ren, T., Wei, K., Zhou, Y., Pan, L., Qin, G., Zhang, Y., & Yu, Y. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4787477 · Cited by 1
Inverse vaccines - Friend, Not Foe: How Inverse Vaccines Tackle Autoimmune DiseasesPreprint
Tenchov, R., & Zhou, Q. A. (2024) · ChemRxiv · doi:10.26434/chemrxiv-2024-m8mk5
Reflections on The Lancet menopause Series
Xiao, Y., Shen, M., & Chen, X. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01711-2 · Cited by 1
Aging-Associated Autoimmunity in Genetically Diverse UM-HET3 Mice Shows a Female Sex BiasPreprint
Guzniczak, N., Makuch, M., Tillett, M., Bagavant, H., & Deshmukh, U. S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.25.666876 · Cited by 1
Editorial: Autoimmunity: novel insights and future perspectives
Neagu, M. T., Ilie, M. A., Mihai, A., & Căruntu, C. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1728233 · Cited by 3
Kriachkov, V. A., Hui, J. C. W., Lancaster, J., Vespasiani, D. M., Denny, N., Hamley, J. C., Gubbels, L., Bandala‐Sanchez, E., Neeland, M. R., Levi, E., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.01.708923 · Cited by 1
Yang, Y., Xie, L., Zhong, Y., Zhong, X., Jiang, S., Du, H., Zhang, X., Yu, L., Shang, J., Fan, J., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3261106/v1
Braun, J., & Karberg, K. (2023) · Zeitschrift für Rheumatologie · doi:10.1007/s00393-023-01411-9
SEASONAL CHARACTERISTICS OF RELAPSING-REMITTING MULTIPLE SCLEROSIS COURSE
Somilo, O. V., & Kalbus, O. I. (2023) · Bulletin of Problems Biology and Medicine · doi:10.29254/2077-4214-2023-3-170-264-271
Кравчун, П. П., Дунаєва, І., Chernyavska, I. V., Oleinikova, S. P., & Kryvoshapka, O. V. (2023) · INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine) · doi:10.22141/2224-0721.19.6.2023.1316
Network-based biomarker discovery for multiple sclerosis
Åkesson, J. (2023) · Linköping studies in science and technology. Dissertations · doi:10.3384/9789180753968
Advances abound in immune mediated inflammatory diseases
Gravallese, E. M., & McInnes, I. B. (2023) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2023.152318
Serum neurofilaments light chain as a diagnostic marker of multiple sclerosis
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Regulatory T cells control type 1-driven immunopathology restraining GM-CSF-producing helper T cellsPreprint
Costa-Pereira, S., Lanzinger, M., Andreadou, M., Núñez, N. G., Villar-Vesga, J., Prisco, F., Häne, P., Roussel, E., Krishnarajah, S., Lindemann, R. C., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.24.577048
Persistence of Anemia in Celiac Disease patients despite a Gluten Free Diet: A retrospective studyPreprint
Valvano, M., Chiara, G., Vinci, A., Maurici, M., Fabiani, S., Stefanelli, G., Cesaro, N., Viscido, A., Caloisi, C., & Giovanni, L. (2024) · Research Square · doi:10.21203/rs.3.rs-3900703/v1
Mise à jour du diagnostic différentiel et du traitement des douleurs articulaires de la ménopause
Dan, D. (2024) · Rheuma Plus / Schweiz · doi:10.1007/s44332-024-00007-y
Hernangomez‐Laderas, A., Cilleros‐Portet, A., Velasco, S. M., Marí, S., Legarda, M., González‐García, B. P., Tutau, C., García‐Santisteban, I., Irastorza, I., Fernández‐Jiménez, N., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24784602
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Morris, J. A., Rigby, R. J., Wray, M., & Taylor, A. M. (2024) · Food & Nutrition Journal · doi:10.29011/2575-7091.100194
Enthesitis and seronegative arthritis induced by Dupilumab: how relevant are these adverse events?
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AS DOENÇAS AUTOIMUNES PELA ÓTICA DA PSICOLOGIA CORPORAL E TRADICIONAL: UMA REVISÃO INTEGRATIVA
Viana, F. P. (2024) · REVISTA LATINO-AMERICANA DE PSICOLOGIA CORPORAL · doi:10.14295/rlapc.v11i17.183
Editorial: Exploring the role of T helper cells in autoimmune disease
Haghmorad, D., Oksenych, V., & Huszthy, P. C. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1434684
Comorbidités et facteurs pronostiques de la maladie de Sjögren
Beydon, M., & Séror, R. (2024) · Revue du Rhumatisme · doi:10.1016/j.rhum.2024.05.012
Metadata
- 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
- 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
- green
- orca.cardiff.ac.uk
- 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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