For many, white or blue fingertips in the cold is an everyday event in the winter. It can bring a tingling, painful misery on a windy day – or even just during stressful situations.
This article explains the causes of Raynaud’s syndrome and examines the genetic variants that increase susceptibility. I’ll end with the research-backed treatment options in the Lifehacks section.
Raynaud’s Syndrome (or Phenomenon) is an episodic vasospastic disorder causing decreased blood flow and numbness in the fingers and other extremities.
As the blood vessels constrict, it reduces the blood flow to the fingers or other extremities. Cold or stress (physical or mental) can trigger it.
Women are more likely than men to have Raynaud’s syndrome, with some reports of up to 20% prevalence.[ref]
Often Raynaud’s occurs along with other underlying conditions, such as autoimmune diseases or connective tissue disorders. Sometimes Raynaud’s Phenomenon can be ‘primary’ and occur alone.
Many people with Raynaud’s also have migraines, which may link to vasoconstriction.
Symptoms of Raynaud’s
The drastic color changes in the extremities are a tell-tale sign of this syndrome. It is the first symptom that most people notice with Raynaud’s. The tips of the fingers turn very white from the decreased blood flow and then appear blue or cyanotic with cold or stress. These changes are followed by the fingers turning red when warmed up and blood flow returns (or no longer stressed).
Doctors can use cold provocation or placing the hands in cold, to cause the vessels to constrict. Infrared thermography can then determine the extent of the changes in blood flow to the extremities.[ref]
While it is easy to think of Raynaud’s as just ‘fingers turning white in the cold’, restricting blood to the extremities can be very painful and can cause irreversible tissue damage in severe cases.[ref]
Causes of Raynaud’s syndrome
Spasms or constrictions in the blood vessels seem to be the cause of Raynaud’s. It is an exaggeration of the typical response of blood vessels to either cold or emotional stress.[ref]
Some researchers theorize that the cause of the spasms in the blood vessels comes from the impaired functioning of the adrenergic receptors in the vascular muscle cells. Three types of adrenergic receptors are responsible for constricting or relaxing the muscles surrounding the blood vessels. One adrenergic receptor subtype activates with cold and norepinephrine (noradrenaline), which also releases stressful situations.[ref]
The blood vessel spasms can be ‘primary’ or ‘secondary’.
Primary Raynaud’s, often referred to as idiopathic, meaning the cause is unknown. This unknown reason causes the overreaction of the blood vessel constriction to the extremities.
Secondary Raynaud’s is associated with autoimmune diseases, connective tissue disorders, or medication interactions.
Autoimmune diseases that are more likely to cause Raynaud’s include:[ref]
- systemic sclerosis
- systemic lupus erythematosus
- Sjögren’s syndrome
Raynaud’s can be one of the first symptoms of certain autoimmune diseases, giving doctors and patient’s a ‘heads up’ to look for diseases early.[ref]
Talk with your doctor if you have Raynaud’s. Getting a test for specific autoantibodies in autoimmune diseases may help you get quicker treatment. For example, antinuclear antibodies often help diagnose these autoimmune diseases (lupus, Sjögren’s, and systemic sclerosis). Other antibodies can indicate antisynthetase syndrome. “The antisynthetase syndrome (ASSD) is an autoimmune disorder characterized by myositis, arthritis, mechanic’s hands, fever, Raynaud phenomenon, and interstitial lung disease (ILD).”[ref]
Related Article: Genetics and Ehlers Danlos Syndrome
Triggers of Raynaud’s Syndrome
The reduction of blood flow in the extremities seen in Raynaud’s phenomenon can be triggered by:[ref]
- chemical exposure
- repetitive actions
- Vibrations (using tools such as a jackhammer)
Cold: A natural reaction to cold is for blood vessels in the fingers and toes to constrict. But in Raynaud’s, the constriction doesn’t ease and is more exaggerated than normal.
Medications: Several classes of medications can cause Raynaud’s phenomenon. The highest risk occurs with cisplatin and bleomycin, but β‐adrenoceptor blockers (a.k.a beta-blockers) are a very common medication that may cause Raynaud’s in some people. For others, migraine medications, such as triptans, have links to Raynaud’s.[ref]
Vibration: Vibration white finger is often the term applied to Raynaud’s syndrome caused by mechanical vibration. People who work with vibrating machinery are at about a 4-fold increased risk of Raynaud’s.[ref]
Why is Raynaud’s found more commonly in women?
Researchers think that Raynaud’s may be more common in premenopausal women due to estrogen’s impact on vasoconstriction through the α2C-AR (alpha(2C)-adrenoceptors) receptors located in blood vessels. Estrogen also plays a role in regulating body temperature. Research shows that post-menopausal women on estrogen-only hormone replacement therapy also have a higher incidence of Raynaud’s.[ref][ref]
Is Raynaud’s syndrome genetic?
Research shows that Raynaud’s runs in families and seems to be about 30% hereditary.[ref][ref] This means that genetic variants increase the susceptibility to Raynauds, but there isn’t a single gene mutation or variant that causes it by itself. Like most conditions, Raynaud’s is likely due to genetic susceptibility combined with a triggering factor.
The genetics section below highlights some genetic variants associated with an increased relative risk of Raynaud’s.
Raynaud’s syndrome and COVID-19 vaccination
Case reports of Raynaud’s after SARS-CoV-2 vaccination include a 31-year-old woman with a new onset of Raynaud’s after the vaccine.[ref] The VAERS database also lists (as of Sept. 2021) 179 cases of Raynaud’s coinciding with the SARS-CoV-2 vaccines. To see this reference, go to medalerts.org and search for Raynaud’s symptoms and COVID-19 vaccines.
Keep in mind that it could be entirely coincidental for Raynaud’s to occur post-vaccine. The 179 reports in VAERS are not all that many in comparison to other post-vaccination symptoms.
Genetic variants linked to Raynaud’s Syndrome
NOS1 gene: encodes nitric oxide synthase, which contracts blood vessels and is responsive to cold
Check your genetic data for rs527590 (AncestryDNA):
- T/T: increased susceptibility to Raynaud’s syndrome[ref]
- C/T: increased susceptibility to Raynaud’s syndrome
- C/T: typical
Members: Your genotype for rs527590 is —.
Genes associated with autoimmune reactions have links to Raynaud’s phenomenon, perhaps through the severity of the autoimmune disease.
IL1B gene: encodes the interleukin 1beta inflammatory cytokine
Check your genetic data for rs1143634 (23andMe v4, v5; AncestryDNA):
- G/G: increased risk of antisynthetase syndrome (autoimmune disorder w/Raynaud’s)[ref]
- A/G: increased risk of antisynthetase syndrome (autoimmune disorder w/Raynaud’s)
- A/A: typical
Members: Your genotype for rs1143634 is —.
INFG: Interferon-gamma gene, important in the initial response to viral infections.
Check your genetic data for rs2069718 (AncestryDNA):
- G/G: increased risk of Raynaud’s in connective tissue disorder patients[ref]
- A/G: typical risk
- A/A: typical risk
Members: Your genotype for rs2069718 is —.
TNF gene: encodes the TNF-alpha inflammatory cytokine
Check your genetic data for rs1800630 (23andMe v4, v5; AncestryDNA):
- A/A: increased risk of Raynaud’s in lupus patients[ref]
- A/C: increased risk of Raynaud’s in lupus patients[ref]
- C/C: typical
Members: Your genotype for rs1800630 is —.
HTR1B gene: encodes a serotonin receptor
Check your genetic data for rs6297 (23andMe v4; AncestryDNA):
- C/C: increased risk of Raynaud’s due to hand/arm vibrations[ref]
- C/T: increased risk of Raynaud’s due to hand/arm vibrations
- T/T: typical
Members: Your genotype for rs6297 is —.
Treatments for Raynaud’s
Keep your fingers warm in the cold weather. This advice was given for Raynaud’s in 1908 and is still valid today. Wear gloves, and take finger heaters with you. They even make little rechargeable heaters that you can put in your pockets in cold weather.
Talk with your doctor about medication options for Raynaud’s phenomenon. If you aren’t already diagnosed with an autoimmune disease, ask whether this could be an indicator of an underlying autoimmune condition.
Stop smoking. Smoking promotes vasoconstriction and may make Raynaud’s worse.
l-Arginine is an amino acid available as a supplement. Research shows that l-arginine may help with nitric oxide synthase production and decrease the vasoconstriction seen in Raynauds. One journal article concludes that “studies of oral l‐arginine in secondary RP suggest that divided dosing may begin at 1–2 g/day and may be titrated up to 10 g/day.” [ref]
Beetroot juice, which contains nitrates and may increase nitric oxide, has also been shown to help with vascular spasms due to cold.[ref]
N-Acetyl Cysteine has been shown in a clinical trial to decrease Raynaud’s phenomenon episodes by about half.[ref]
Medication interactions: If you are currently on medications, ask your doctor whether the drug is causing your Raynaud’s.
An Acupuncture/acupressure point, Hegu or LI4, may be important in Raynaud’s. Research shows that activating that acupuncture points may bring relief for some people. Alternatively, you may also want to try acupressure on that point.[ref]
Member’s Blueprint: Next Steps and Experiments
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Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.