Researchers say about 1 in 10 individuals are now affected by autoimmune disorders and reveal new clues on possible causes.
There are more than 80 types of autoimmune diseases known, with common examples including rheumatoid arthritis, type 1 diabetes, and multiple sclerosis.
"Some autoimmune disorders, such as type 1 diabetes, are reported to have increased over the past several decades," said the authors of a new study published in The Lancet.
However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are "scarce and inconsistent", they pointed out.
This, they said, raised the question as to whether the overall incidence of autoimmune disorders was on the rise, "driven perhaps by common environmental factors or behavioural changes".
The authors also pointed out that because individual autoimmune diseases are rare, and because there are so many different types, it had been very difficult to undertake sufficiently large studies and establish reliable estimates, and to answer certain questions, one of which was the exact causes of autoimmune diseases, particularly with respect to relative contributions of genetic predisposition or environmental factors. This remained "largely a mystery", the authors said.
Professor Geraldine Cambridge, from University College London (UCL) and senior author, emphasised how: "Disentangling the commonalities and differences within this large and varied set of conditions is a complex task."
Incidence Rates Increasing
In an attempt to try and answer some of the unanswered questions, a consortium of experts in epidemiology, biostatistics, rheumatology, endocrinology, and immunology, from UCL, Glasgow University, Imperial College London, Cardiff University, Leicester University, Oxford University, and KU Leuven in Belgium, joined forces. They set out to investigate the incidence and prevalence of nineteen of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and examine rates of co-occurrence among autoimmune diseases.
For the UK population-based study, they used data from the Clinical Practice Research Datalink (CPRD) of over 22 million people between 2000 and 2019. Eligible participants were men and women – with 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 twelve months during the study period.
The researchers examined whether cases of autoimmune diseases were rising over time, who was most affected by these conditions and how different autoimmune diseases co-existed with each other.
Of the 22,009,375 individuals included in the study, almost one million (978,872) had a new diagnosis of at least one autoimmune disease between 30 June 2019 and 1 January 2000. The mean age was 54 years, and almost 2 out of 3 (63.9%) of those diagnosed individuals were female (36.1% male).
"Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased," highlighted the authors. The incidence rate ratio (IRR) for 2017-19 versus 2000-02 was 1.04 (95% CI 1.00 to 1.09). The researchers found the largest increases were in coeliac disease (2.19), Sjogren's syndrome (2.09), and Graves' disease (2.07).
Pernicious anaemia (0.79) and Hashimoto's thyroiditis (0.81) significantly decreased in incidence, they said.
Previous estimates for the prevalence of autoimmune disorders had ranged from 3-9%, the authors said. However, the study found that added together, the 19 autoimmune disorders examined affected 10.2% of the population over the study period – 13.1% women and 7.4% men.
Seasonal Variation
The researchers also highlighted socioeconomic, seasonal, and regional differences for several autoimmune disorders, which they said provided "new clues" for possible causes behind these diseases.
"A socioeconomic gradient was evident across several diseases," commented the authors. Specifically, the risk with regards most versus least deprived areas, was greater for pernicious anaemia (IRR 1.7), rheumatoid arthritis (1.52), Graves' disease (1.36), and systemic lupus erythematosus (1.35).
Seasonal variations were observed for childhood-onset type 1 diabetes, which was more commonly diagnosed in winter, and vitiligo, which was more commonly diagnosed in summer. The researchers also said that regional variations were observed for a range of conditions.
Such variations were unlikely to be attributable to genetic differences alone and may point to the involvement of potentially modifiable risk factors such as smoking, obesity, or stress that contribute to the development of some autoimmune diseases, they suggested.
Common Risk Factors Shared
Commenting on their findings the researchers expressed that in some cases a person with one autoimmune disease was more likely to develop a second compared to someone without an autoimmune disease.
"Autoimmune disorders were commonly associated with each other," they explained, 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), coeliac disease (28.4), and thyroid disease – Hashimoto's thyroiditis (13.3) and Graves' disease (6.7). Multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases, the authors highlighted.
Dr Nathalie Conrad, from Deep Medicine at Nuffield Dept of Women's and Reproductive Health at the University of Oxford, and first author of the paper, said: "We observed that some autoimmune diseases tended to co-occur with one another more commonly than would be expected by chance or increased surveillance alone.
"This could mean that some autoimmune diseases share common risk factors, such as genetic predispositions or environmental triggers," she suggested.
She stressed that this was particularly visible among rheumatic diseases and among endocrine diseases, but the phenomenon was not generalised across all autoimmune diseases. "Multiple sclerosis for example, stood out as having low rates of co-occurrence with other autoimmune diseases, suggesting a distinct pathophysiology," she postulated.
Professor Cambridge underlined how the study highlighted the "considerable burden" that autoimmune diseases placed upon individuals and the wider population.
"There is a crucial need, therefore, to increase research efforts aimed at understanding the underlying causes of these conditions, which will support the development of targeted interventions to reduce the contribution of environmental and social risk factors," she urged.
Funding for the study was provided by Research Foundation Flanders.