Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status

[helvella]

Just saw this and thought it needed posting - but I haven't got beyond the title yet!

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

Nathalie Conrad, Shivani Misra, Jan Y Verbakel, Geert Verbeke, Geert Molenberghs, Peter N Taylor, Justin Mason, Naveed Sattar, John J V McMurray, Iain B McInnes, Kamlesh Khunti, Geraldine Cambridge,

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.

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, The Lancet, 2023, ISSN 0140-6736, doi.org/10.1016/S0140-6736(....

sciencedirect.com/science/a...

[humanbean]

Hashimoto's thyroiditis (0·81 [0·75–0·86]) significantly decreased in incidence.

I wonder if this could be because doctors won't diagnose until TSH is greater than 10.

[helvella Administrator in reply to humanbean]

I was going to go back and look properly! Need to check their terminology - Hashimoto's vs. Ord's vs. Autoimmune Thyroid Disease. I was just too keen to post!

[helvella Administrator in reply to helvella]

The paper declares Hashimoto's defined by:

Individuals with Hashimoto’s thyroiditis were identified as those with at least one levothyroxine prescription and no history of hyperthyroidism, pituitary disease, thyroid surgery, or thyroid-altering medication (eg, amiodarone, lithium, sodium valproate, carbimazole, propylthiouracil, thalidomide, or sunitinib).

Therefore, I have Hashimoto's despite:

No-one ever considering pituitary disease;

And negative antibodies.

I can understand that they might have felt they had to use such a definition but it isn't very satisfactory.

[LindaC]

Thank you, helvella - most interesting!

[Zephyrbear]

Peter N Taylor (one of the co-authors) posted a link to this on Twitter either yesterday or the day before and I did read it, meaning to post a link here and then forgot… a very interesting read although, as mentioned above, I too wondered why the figures for hypothyroidism would be down. One of my daughters, thankfully, got a diagnosis and treatment with her TSH at 5.4 because of my history (we’re both with the same GP surgery). How much permanent damage to me could have been avoided had I had the same instead of having to wait until my TSH hit the “magic” 10!

[helvella Administrator in reply to Zephyrbear]

Any change to diagnostic criteria will affect the numbers. Some changes will tend to delay diagnosis, others might mean it is impossible.

As you say, the TSH = 10 issue will have a significant effect. Delaying some and ensuring others don't get diagnosed before something else comes along.

Also, if we accept that some have TPO antibodies only, others TG antibodies only, and some have both. Anyone in TG only could be missed due to never being tested.

Also, misdiagnosis plays its part. We keep seeing some being told they have Graves when it looks far more like a Hashimoto's flare.

And there is the ongoing "It can't be Hashimoto's because you don't have a goitre". Which can work both ways. - Is all autoimmune thyroid destruction now classed as Hashimoto's? Has Ord's been consigned to the scrapheap?

[Zephyrbear in reply to helvella]

I never had a goitre or significant levels of antibodies, even when I was finally diagnosed… so mine would presumably have been Ord’s rather than Hashimoto’s. When my thyroid was scanned just after getting my diagnosis, it was found to have shrivelled to almost nothing, certainly not in the business of producing any useful levels of thyroid hormones at all. Little wonder I felt as though I was just able to drag my carcass around anywhere and bed felt the best place to be… then followed 7 years of ever increasing, but ultimately useless T4 monotherapy before my endo finally gave me a trial of T3 and I got my life back!