Marie’s Disease is More Common The Farther North You Go – Now Researchers Are Looking For Answers

"For many years, they thought the pain, fatigue and inflammation were caused by overexertion from training and football. But it never went away," Marie Dahlskjær (32) tells High North News.

In her appartment in downtown Bodø, Northern Norway, she describes a childhood marked by severe pain, hospital stays, and long absences from school.

It was not until she was 12 that her symptoms were finally explained. Dahlskjær was diagnosed with both juvenile arthritis and the connective tissue disease scleroderma.

Both are autoimmune diseases – conditions where the immune system malfunctions and attacks the body’s own tissue.

Dahlskjær’s story is also part of a wider geographical pattern.

Several autoimmune diseases occur more frequently in Northern Norway than further south in the country.

Researchers are now trying to understand what lies behind this geographical pattern.

A clear north-south divide

"The difference is greatest for juvenile arthritis. There, we see that the incidence is 83 percent higher in Northern Norway compared with Southern Norway," says professor and physician Ketil Størdal at the University of Oslo to High North News.

Størdal has supervised and co-authored research investigating geographical differences in autoimmune diseases among children.

The pattern is not limited to juvenile arthritis. The researchers have also found regional differences in conditions including inflammatory bowel disease (IBD) and type 1 diabetes.

In addition, research dating back to 2014 has shown that the risk of developing multiple sclerosis (MS) increases with latitude.

And the phenomenon does not stop at Norway's borders.

According to Størdal, differences between northern and southern parts of both the United Kingdom and Germany have been reported for juvenile arthritis. In Finland, higher rates of inflammatory bowel disease has also been found in the north.

"We see a compelling link with living closer to the poles," Størdal concludes.

It was only after learning about the research that Dahlskjær began to view her own illness from a geographical perspective.

"Once I became aware of these differences, I started thinking more and more about why so many people here in Northern Norway are affected."

However, even though the pattern is clear, the underlying cause is far harder to pinpoint.

Could it be the sun?

When researchers look for an explanation for why prevalence increases towards the north, sunlight and vitamin D are among the factors that naturally come to mind.

Northern Norway has long periods of limited sunlight during the winter, and the body produces vitamin D when the skin is exposed to sunlight.

Researchers have therefore investigated whether vitamin D levels early in life could explain some of the difference.

"We have measured vitamin D in relation to diabetes, coeliac disease and inflammatory bowel disease, and it does not explain the differences. So, early in life, we do not see any association between vitamin D and these diseases," Størdal explains.

But Størdal is not ruling out sunlight.

"In addition to vitamin D, there may be other aspects of sunlight and climatic conditions that matter. These are things we are currently working to study."

Whether such factors actually affect the risk of developing disease remains an open question. For Dahlskjær, however, the climate is already a very tangible part of living with her conditions.

She notices it particularly when winter arrives.

"I live in the wrong place, I have to admit. You become very stiff and experience more pain in winter, and warmth is something that helps. So I spend a lot of energy adapting and making arrangements for myself."

On her worst days, her morning routine can take several hours. A hot shower, heat treatment and the right medication at the right time are necessary before her body function the way she wants it to.

The weather does not necessarily have to be at its coldest to be challenging. For Dahlskjær, fluctuating temperatures can be worse than steady cold.

"If it's minus 15 degrees celcius and there's snow that remains stable for a month, that's actually better than when the temperature keeps changing."

Genes explain some of it - the environment may explain more

Sunlight is only one possible piece of the puzzle. Researchers have also investigated whether the differences could be related to the characteristics of the people living in the north.

They have adjusted for factors including education, income, the mother's age, number of children, caesarean section and whether the mother was born abroad. The differences remain even after these adjustments.

Perhaps the explanation lies in the genes?

"For juvenile arthritis, we have seen that genetics explain some of the differences between north and south. But for the other diseases, such as IBD and diabetes, there are still things we are working to understand," Størdal says.

Researchers are now investigating whether the Arctic environment itself and the conditions children grow up in in the north may affect the immune system early in life.

"It is possible that living in cold regions, where winters last longer and the ground is frozen and covered in snow, could influence the development of the gut microbiome early in life," he elaborates.

Størdal stresses that they are unlikely to find a single cause:

"I think it is an interplay between several factors, and that the explanation will vary between the different diseases."

Overlap between diseases

There is also another feature of these diseases that may provide researchers with clues. A new study shows that children who develop one autoimmune disease are more likely to develop others.

"We have seen that the six diseases we studied, which are the most common autoimmune diseases in children, have quite a substantial degree of overlap," Størdal says.

Dahlskjær is one of those affected by more than one autoimmune disease.

"I know several people who also have more than one diagnosis. It is very interesting to think about why that is. There are probably many factors at play."

Genetics may again be part of the explanation. Certain genetic variants can make a person more susceptible to several autoimmune diseases at the same time.

"For example, we know that in diabetes and coeliac disease, many of the same genetic variants increase your risk of developing both. But shared environmental factors may also explain some of the overlap we see, says Størdal.

Here, too, the picture is complex. Genetics may explain some aspects, while environmental and other factors may contribute to other parts of the disease picture.

For Dahlskjær, there is nevertheless one thing that has changed since she was a child: the level of knowledge about these conditions.

"There wasn't much research into juvenile arthritis when I was young. But in recent years, I feel it has increased enormously. That's fantastic for young people today, who can receive the right medication early on,” she concludes.