Raynaud’s Syndrome – When Fingers Turn White and Blue
Summary
- Raynaud’s syndrome, a vascular disorder affecting extremities, leads to noticeable colour changes predominantly in fingers and toes.
- With approximately 5% of the population affected, the disorder is common.
- Primary Raynaud’s is less severe and often lacks an underlying medical condition, while secondary Raynaud’s is associated with autoimmune disease.
In our most recent Facts&Reason article, we explored the autoimmune disease Scleroderma (click here to read it). As for many autoimmune diseases, Scleroderma has associated diseases, called comorbidities; one such comorbidity is Raynaud’s syndrome.
Raynaud’s syndrome is named after the French doctor Maurice Raynaud, who first described it in 1862 and is rather common, with about 5% of the population affected [1]. Raynaud’s syndrome is a vascular disorder characterised by episodes where blood stops flowing into the extremities, predominantly the fingers and toes. The hallmark of Raynaud’s syndrome is a noticeable change in skin colour, with affected areas turning white, then blue. This is due to reduced blood flow, followed by redness and throbbing pain as blood flow returns.
Triggers of Raynaud's Episodes
Raynaud’s happens in episodes in which blood flow to extremities is temporarily lost. These episodes are also called Raynaud’s attack. This is generally associated with an exaggerated response to cold, emotional stress, or mechanical impact, like vibration from drills. The duration of each episode can last from a few minutes to up to hours [1].
Types of Raynaud’s Syndrome
The condition can be classified into two main types: primary and secondary [2].
Primary Raynaud’s, also known as Raynaud’s disease, is the least severe form and is the most common one, with 80% of people affected. Primary Raynaud’s is usually not caused by other diseases or underlying medical conditions, i.e. it is not secondary to another condition. The precise cause often remains unknown, but it is believed that abnormalities in blood vessels or the nervous system may contribute to the exaggerated response to cold or stress. For some patients, it might be that the sympathetic nervous system, which controls vasoconstriction, overreacts and leads to blood vessels constricting. Other causes could be for example medications, such as beta-blockers.
Secondary Raynaud’s, or Raynaud’s phenomenon, is associated with other diseases, most notably autoimmune disease and connective tissue disorders such as Scleroderma [3] and lupus. Connective tissue disorders can cause structural changes in blood vessels, contributing to the vascular abnormalities observed in secondary Raynaud’s. Short-term temporary changes include for example blood vessels constricting during an episode, while longer-term impacts include blood vessel inflammation, pattern changes, and cell death. While short-term changes are also seen in primary Raynaud’s, longer-term impacts are typically only observed in secondary Raynaud’s.
While primary Raynaud’s is generally less severe and does not lead to serious complications, secondary Raynaud’s can pose significant health risks. In mild cases, individuals may experience occasional episodes, and the symptoms may resolve on their own. In more severe cases, Raynaud’s can lead to complications such as ulcers, sores, and infections. In extreme cases, it may result in tissue damage, gangrene, or loss of digits [4]. Additionally, if Raynaud’s is associated with an underlying autoimmune disease or connective tissue disorder, managing the primary condition, for example by immunosuppression, becomes crucial to prevent further complications.
Prevalence in Women
Raynaud’s syndrome is more prevalent in women, as is the case for the majority of autoimmune conditions. In fact, in some diseases, the ratio can be as high as 19:1. New work from Stanford University suggests that the reason for the prevalence in women is in our DNA [5]. Women have two X-chromosomes, but only one of them is needed for biological function, meaning the other X-chromosome gets inactivated. This inactivation is called silencing and is achieved by factors that modulate the DNA, specifically by a factor called long noncoding RNA Xist. Researchers have now found that Xist is directly linked to autoimmune diseases and while many other factors play into autoimmune diseases, Xist is a meaningful candidate for understanding autoimmunity and for clinical investigations.
In addition to genetic causes, also hormonal factors may play a role. Estrogen, for instance, is thought to influence blood vessel function and responsiveness, potentially contributing to the increased incidence of Raynaud’s in women [6].
Recent Research Breakthroughs
Although there is a lot of research about disease causes and progression, there are still a lot of unknowns. The most recent breakthrough was published in October 2023, where scientists discovered variations of two genes to be associated with Raynaud’s syndrome (alpha-2A-adrenergic receptor for adrenaline (ADRA2A) and transcription factor IRX1). This study is exciting as it showcases a genetic prevalence for the disease [7]. This means that patients could potentially receive treatments specific to these genetic alterations, or other causes of Raynaud’s, which means that more specific treatments can be used with fewer side-effects and often lower doses of medication.
Conclusion
In conclusion, Raynaud’s syndrome is a vascular disorder characterised by episodic colour changes in the extremities, most commonly the fingers and toes, which can be painful. While primary Raynaud’s is more common and less severe, secondary Raynaud’s is associated with other underlying health conditions. The prevalence of Raynaud’s is higher in women, and understanding the underlying causes and potential complications is crucial for its effective management. Early diagnosis and appropriate medical intervention can help individuals with Raynaud’s lead fulfilling lives while minimising the risk of complications.
If you are interested in learning more about Raynaud’s as a secondary disease, make sure to read our earlier article on the autoimmune disease Scleroderma here.
References
- A. L. Herrick and F. M. Wigley, “Raynaud’s phenomenon,” Best Practice & Research Clinical Rheumatology, vol. 34, no. 1, p. 101474, Feb. 2020, doi: 10.1016/j.berh.2019.101474.
- J. D. Pauling, M. Hughes, and J. E. Pope, “Raynaud’s phenomenon—an update on diagnosis, classification and management,” Clin Rheumatol, vol. 38, no. 12, pp. 3317–3330, Dec. 2019, doi: 10.1007/s10067-019-04745-5.
- M. Maciejewska, M. Sikora, C. Maciejewski, R. Alda-Malicka, J. Czuwara, and L. Rudnicka, “Raynaud’s Phenomenon with Focus on Systemic Sclerosis,” Journal of Clinical Medicine, vol. 11, no. 9, Art. no. 9, Jan. 2022, doi: 10.3390/jcm11092490.
- K. K. Temprano, “A Review of Raynaud’s Disease,” Mo Med, vol. 113, no. 2, pp. 123–126, 2016.
- Dou DR, Zhao Y, Belk JA, Zhao Y, Casey KM, Chen DC, Li R, Yu B, Srinivasan S, Abe BT, Kraft K, Hellström C, Sjöberg R, Chang S, Feng A, Goldman DW, Shah AA, Petri M, Chung LS, Fiorentino DF, Lundberg EK, Wutz A, Utz PJ, Chang HY. Xist ribonucleoproteins promote female sex-biased autoimmunity. Cell. 2024 Feb 1;187(3):733-749.e16. doi: 10.1016/j.cell.2023.12.037. PMID: 38306984; PMCID: PMC10949934.
- I. Serizawa, N. Iwasaki, H. Ishida, S.-Y. Saito, and T. Ishikawa, “G-protein coupled estrogen receptor-mediated non-genomic facilitatory effect of estrogen on cooling-induced reduction of skin blood flow in mice,” Eur J Pharmacol, vol. 797, pp. 26–31, Feb. 2017, doi: 10.1016/j.ejphar.2017.01.013.
- S. Hartmann et al., “ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon,” Nat Commun, vol. 14, no. 1, Art. no. 1, Oct. 2023, doi: 10.1038/s41467-023-41876-5.