Raynaud syndrome, also known asRaynaud's phenomenon, is amedical condition in which thespasm of small arteries causes episodes of reducedblood flow to endarterioles.[1] Typically the fingers, and, less commonly, the toes, are involved.[1] Rarely, the nose, ears, nipples, or lips are affected.[1] The episodes classically result in the affected part turningwhite and thenblue.[2] Often,numbness or pain occurs.[2] As blood flow returns, the area turns red and burns.[2] The episodes typically last minutes but can last several hours.[2] The condition is named after the physicianAuguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862.[6]
Episodes are typically triggered by cold or emotional stress.[2] Primary Raynaud's isidiopathic (spontaneous and of unknown cause) and not correlated with another disease. Secondary Raynaud's is diagnosed given the presence of an underlying condition and is associated with an older age of onset.[3] In comparison to primary Raynaud's, episodes are more likely to be painful, asymmetric and progress to digital ulcerations.[7] Secondary Raynaud's can occur due to aconnective-tissue disorder such asscleroderma orlupus, injuries to the hands,prolonged vibration, smoking,thyroid problems, and certain medications, such asbirth control pills andstimulants.[8] Diagnosis is typically based on the symptoms.[3]
The primary treatment is avoiding the cold.[3] Other measures include the discontinuation of nicotine orstimulant use.[3] Medications for treatment of cases that do not improve includecalcium channel blockers andiloprost.[3] There is little evidence thatalternative medicine is helpful.[3] Severe disease may in rare cases lead to complications, specificallyskin sores organgrene.[2]
About 4% of people have the condition.[3] Onset of the primary form is typically between ages 15 and 30. The secondary form usually affects older people.[4] Both forms are more common in coldclimates.[4]
Raynaud's affecting all five fingersBluish coloration
The condition can cause localized pain, discoloration (paleness), and sensations of cold and/or numbness.
When exposed to cold temperatures, the blood supply to the fingers or toes, and in some cases the nose or earlobes, is markedly reduced; the skin turns pale or white (calledpallor) and becomes cold and numb.These events are episodic, and when the episode subsides or the area is warmed, the blood flow returns and the skin color first turns red (rubor), and then back to normal, often accompanied byswelling, tingling, and a painful "pins and needles" sensation. All three color changes are observed in classic Raynaud's yet not all patients see all of the aforementioned color changes in all episodes, especially in milder cases of the condition. The red flush is due to reactivehyperemia of the areas deprived of blood flow.
Inpregnancy, this sign normally disappears due to increased surface blood flow. Raynaud's has occurred in breastfeeding mothers, causing nipples to turn white and painful.[9]
Raynaud's disease, or primary Raynaud's, is diagnosed if the symptoms areidiopathic, that is, if they occur by themselves and not in association with other diseases. Some refer to primary Raynaud's disease as "being allergic to coldness". It often develops in young women in their teens and early adulthood. Primary Raynaud's is thought to be at least partlyhereditary.[10] In a large genetic study two genes were identified that predispose for the condition:ADRA2A (alpha-2A-adrenergic receptor for adrenaline) and the transcription factor IRX1.[11]
Smoking increases the frequency and intensity of attacks, and a hormonal component exists.Caffeine, estrogen, and nonselective beta-blockers are often listed as aggravating factors, but evidence that they should be avoided is not solid.[12]
Erythromelalgia (clinically presenting as the opposite of Raynaud's, with hot and warm extremities, often co-exists in patients with Raynaud's[17])
Chilblains (also clinically presenting as the opposite of Raynaud's, with hot and itchy extremities; however, it affects smaller areas than erythromelalgia, for instance, the tip of a toe rather than the whole foot)
Raynaud syndrome can precede these other diseases by many years, making it the first presenting symptom. This may be the case in theCREST syndrome, of which Raynaud's is a part.[citation needed]
Patients with secondary Raynaud's can also have symptoms related to their underlying diseases. Raynaud's phenomenon is the initial symptom that presents for 70% of patients withscleroderma, a skin and joint disease.[citation needed]
When Raynaud's phenomenon is limited to one hand or one foot, it is referred to as unilateral Raynaud's. This is an uncommon form, and it is always secondary to local or regional vascular disease. It commonly progresses within several years to affect other limbs as the vascular disease progresses.[18]
Three main changes are seen in the mechanism of Raynaud's phenomenon which are reduced blood flow, blood vessel constriction, and neurogenic, inflammatory, and immune responses. It is induced by mental stress and a cold atmosphere. In all cases, the primary cause is an underlying hyperactivation of thesympathetic nervous system.[19] Although, with different types, the exact pathophysiology differs. In the primary type, there is an increase in sensitivity due to the reasons mentioned above resulting invasoconstriction. In the secondary type, normal activity of blood vessels is disrupted due to the same reasons mentioned above causing vasoconstriction which leads toischemia andtissue death.[20]
Thermogram depicting a Raynaud's hand (top) and a healthy hand (bottom): Red indicates warm areas whilst green indicates cool areas.Consensus diagnostic criteria
Distinguishing Raynaud's disease (primary Raynaud's) from Raynaud's phenomenon (secondary Raynaud's) is important. Looking for signs ofarthritis orvasculitis, as well as several laboratory tests, may separate them. Nail fold capillary examination or "capillaroscopy" is one of the most sensitive methods to diagnose RS with connective tissue disorders, i.e. distinguish a secondary from a primary form objectively.[21]
If suspected to be secondary tosystemic sclerosis, one tool which may help aid in the prediction of systemic sclerosis is thermography.[22]
A careful medical history will seek to identify or exclude possible secondary causes.
Digital artery pressures are measured in the arteries of the fingers before and after the hands have been cooled. A decrease of at least 15mmHg is diagnostic (positive).
To aid in the diagnosis of Raynaud's phenomenon, multiple sets of diagnostic criteria have been proposed.[23][24][25][26] Table 1 below provides a summary of these various diagnostic criteria.[27]
Recently, International Consensus Criteria were developed for the diagnosis of primary Raynaud's phenomenon by a panel of experts in the fields of rheumatology and dermatology.[27]
Secondary Raynaud's is managed primarily by treating the underlying cause, and as primary Raynaud's, avoiding triggers, such as cold, emotional and environmental stress, vibrations, and repetitive motions, and avoiding smoking (including passive smoking) andsympathomimetic drugs.[28]
Medications can be helpful for moderate or severe disease.
Vasodilators –calcium channel blockers, such as thedihydropyridinesnifedipine oramlodipine, preferably slow-release preparations – are often first-line treatment.[28] They have the common side effects of headache, flushing, and ankleedema, but these are not typically of sufficient severity to require cessation of treatment.[29] The limited evidence available shows that calcium-channel blockers are only slightly effective in reducing how often the attacks happen.[30] Although, other studies also reveal that CCBs may be effective at decreasing the severity of attacks, pain, and disability associated with Raynaud's phenomenon.[31] People whose disease is secondary toerythromelalgia often cannot use vasodilators for therapy, as they trigger 'flares' causing the extremities to become burning red due to too much blood supply.
People with severe disease prone to ulceration or large artery thrombotic events may be prescribed aspirin.[28]
Statins have a protective effect on blood vessels, andSSRIs such asfluoxetine may help symptoms, but the data is weak.[28]
PDE5 inhibitors, such assildenafil andtadalafil, are used off-label to treat severe ischemia and ulcers in fingers and toes for people with secondary Raynaud's phenomenon; as of 2016, their role more generally in Raynaud's was not clear.[36]
In severe cases, anendoscopic thoracic sympathectomy procedure can be performed.[37] Here, the nerves that signal the blood vessels of the fingertips to constrict are surgically cut.Microvascular surgery of the affected areas is another possible therapy, but this procedure should be considered as a last resort.
A more recent treatment for severe Raynaud's is the use ofbotulinum toxin. The 2009 article[38] studied 19 patients ranging in age from 15 to 72 years with severe Raynaud's phenomenon of which 16 patients (84%) reported pain reduction at rest; 13 patients reported immediate pain relief, three more had gradual pain reduction over 1–2 months. All 13 patients with chronic finger ulcers healed within 60 days. Only 21% of the patients required repeated injections. A 2007 article[39] describes similar improvement in a series of 11 patients. All patients had significant relief of pain.
The prognosis of primary Raynaud syndrome is often very favorable, with no mortality and little morbidity overall. In some very rare cases,gangrene has been known to develop. The prognosis of secondary Raynaud is related to the course of the underlying disease, and how effective blood flow-restoring maneuvers are.[40]
^abc"Who Is at Risk for Raynaud's?".nhlbi.nih.gov. US: National Heart, Lung, and Blood Institute, National Institutes of Health. 21 March 2014.Archived from the original on 5 October 2016. Retrieved1 October 2016.
^"What Causes Raynaud's?".nhlbi.nih.gov. US: National Heart, Lung, and Blood Institute, National Institutes of Health. 21 March 2014.Archived from the original on 4 October 2016. Retrieved1 October 2016.
^Holmen OL, Backe B (2009). "An underdiagnosed cause of nipple pain presented on a camera phone".BMJ.339: b2553.doi:10.1136/bmj.b2553.S2CID71701101.
^Wigley FM, Flavahan NA (10 August 2016). "Raynaud's Phenomenon".New England Journal of Medicine.375 (6):556–565.doi:10.1056/nejmra1507638.PMID27509103.
^Goldman W, Seltzer R, Reuman P (2008). "Association between treatment with central nervous system stimulants and Raynaud's syndrome in children: A retrospective case–control study of rheumatology patients".Arthritis & Rheumatism.58 (2):563–566.doi:10.1002/art.23301.PMID18240233.
^Berlin AL, Pehr K (March 2004). "Coexistence of erythromelalgia and Raynaud's phenomenon".Journal of the American Academy of Dermatology.50 (3):456–60.doi:10.1016/S0190-9622(03)02121-2.PMID14988692.
^Priollet P (October 1998). "[Raynaud's phenomena: diagnostic and treatment study]".La Revue du Praticien (in French).48 (15):1659–64.PMID9814067.
^Musa R, Qurie A (2022),"Raynaud Disease",StatPearls, Treasure Island (FL): StatPearls Publishing,PMID29763008,archived from the original on 29 November 2022, retrieved15 December 2022
^Brennan P, Silman A, Black C (May 1993). "Validity and reliability of three methods used in the diagnosis of Raynaud's phenomenon. The UK Scleroderma Study Group".British Journal of Rheumatology.32 (5):357–361.doi:10.1093/rheumatology/32.5.357.PMID8495253.
^Wigley FM (September 2002). "Clinical Practice.Raynaud's phenomenon".New England Journal of Medicine.347 (13):1001–1008.doi:10.1056/nejmcp013013.PMID12324557.
^LeRoy EC, Medsger TA (September–October 1992). "Raynaud's phenomenon: a proposal for classification".Clinical and Experimental Rheumatology.10 (5):485–488.PMID1458701.
^Maricq HR, Weinrich MC (March 1998). "Diagnosis of Raynaud's phenomenon assisted by color charts".Journal of Rheumatology.15 (3):454–459.PMID3379622.
^abcdefgMikuls TR, Canella AC, Moore GF, Erickson AR, Thiele GM, O'Dell JR (2013). "Connective Tissue Diseases".Rheumatology. London: Manson Publishing. p. 117.ISBN978-1-84076-173-3.
^Smith CR, Rodeheffer RJ (January 1985). "Raynaud's phenomenon: pathophysiologic features and treatment with calcium-channel blockers".The American Journal of Cardiology.55 (3):154B –157B.doi:10.1016/0002-9149(85)90625-3.PMID3881908.
^Pancera P, Sansone S, Secchi S, Covi G, Lechi A (November 1997). "The effects of thromboxane A2 inhibition (picotamide) and angiotensin II receptor blockade (losartan) in primary Raynaud's phenomenon".Journal of Internal Medicine.242 (5):373–6.doi:10.1046/j.1365-2796.1997.00219.x.PMID9408065.S2CID2052430.
^Linnemann B, Erbe M (2016). "Raynaud's phenomenon and digital ischaemia – pharmacologic approach and alternative treatment options".VASA. Zeitschrift für Gefässkrankheiten.45 (3):201–12.doi:10.1024/0301-1526/a000526.PMID27129065.Phosphodiesterase inhibitors (e.g., sildenafil) can also improve [Raynaud's phenomenon] symptoms and ulcer healing
Bakst R, Merola JF, Franks AG, Sanchez M (October 2008). "Raynaud's phenomenon: pathogenesis and management".Journal of the American Academy of Dermatology.59 (4):633–53.doi:10.1016/j.jaad.2008.06.004.PMID18656283.
