Raynaud's Breakthrough

What is Raynaud's Phenomenon? It is a medical condition caused by reduced blood flow to the fingers - but it can also affect the ears, nose, lips, toes, and knees. This happens because of spasms of the blood vessels in those areas, usually in response to cold, stress, or emotional upset. Women are more likely to have Raynaud's disease than men, and it affects between 2% and 5% of the population. The most common symptom is fingers that turn pale or white and then blue when exposed to cold, or during stress or emotional upset. The fingers can become painful and stiff during this period. Then, once warmed, the fingers turn red and may throb, tingle, or swell.

While there is no cure for Raynaud's syndrome, it can be managed with the proper treatment. Your doctor may recommend things such as avoiding exposure to cold, keeping warm with gloves, socks, scarf, and a hat, and avoiding trauma or vibrations to the hand (such as with vibrating electric tools). If problems continue even with those aids, some doctors may prescribe blood pressure medicines during the winter months to help reduce blood vessel constrictions.

Raynaud's can run in families and is heritable. "About half the people who have primary Raynaud's phenomenon have another first-degree relative who also has Raynaud's," said Dr. Laura Hummers, who co-directs John Hopkins Scleroderma Center. Last year, researchers from Queen Mary University of London's Precision Healthcare Research Institute (PHURI) and the Berlin Institute of Health (BIH) at Charite-Universitatsmedizin Berlin analyzed health data from more than 440,000 people in the UK Biobank (a massive database containing genetic and medical information). The research team identified 5,147 cases of Raynaud's, 68% of which were primary Raynaud's. Another 439,294 records served as controls. The results of the study were published in October 2023 in Nature Communications.

"We identify two distinct genes that point to two distinct mechanisms," said Professor Maik Pietzner, one of the study's lead researchers and chair in health data modeling at Queen Mary University of London's Precision Healthcare University Research Institute. One gene variant (alpha-2A-adrenergic receptor for adrenaline, ADRA2A) affects how blood vessels constrict; the other gene variant (the transcription factor IRX1) affects how blood vessels dilate.

Professor Pietzner expounded on the first gene identified: people with that variant tend to have a high number of a certain receptor for hormones that are released when the body is stressed or cold. These hormones signal the tiny blood vessels in the skin to constrict, which allows blood to flow away from the extremities and toward the body's core and vital organs. One existing drug, the antidepressant mirtazapine, already acts on this receptor and could possibly be repurposed for use in people with Raynaud's.

While this study does have limitations (it was based on diagnostic codes from patient records, which are not always fully reliable, and it was only comprised of those of European descent), experts are hopeful it will lead to more effective treatments for those who suffer from Raynaud's. As one example, the researchers showed that people with a genetic predisposition to low blood sugar levels have an increased risk of Raynaud's phenomenon and therefore patients should possibly avoid longer episodes of low blood sugar.

So what's next? Dr. Emma Blamont, Head of Research for Scleroderma and Raynaud's UK (SRUK), said, "The next step is to confirm these important findings in more diverse population groups and validate the results through functional studies. If successful, these findings could help us unlock more new therapeutic avenues for Raynaud's leading to better, more targeted and kinder treatments." Professor Claudia Langenberg concluded, "I am convinced that our findings provide a path to novel effective medications."