Raynaud syndrome, also known as Raynaud's phenomenon, is a
medical condition in which the
spasm of small arteries causes episodes of reduced
blood flow to end arterioles.[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 turning
white and then
blue.[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 physician
Auguste 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 is
idiopathic (spontaneous and of unknown cause) and not correlated with another disease. Secondary Raynaud's occurs as a result of some other condition and has an older age at onset; episodes are intensely painful and can be asymmetric and associated with skin lesions.[3] Secondary Raynaud's can occur due to a
connective-tissue disorder such as
scleroderma or
lupus, injuries to the hands,
prolonged vibration, smoking,
thyroid problems, and certain medications, such as
birth control pills and
stimulants.[7] Diagnosis is typically based on the symptoms.[3]
The primary treatment is avoiding the cold.[3] Other measures include the discontinuation of nicotine or
stimulant use.[3] Medications for treatment of cases that do not improve include
calcium channel blockers and
iloprost.[3] There is little evidence that
alternative medicine is helpful.[3] Severe disease may in rare cases lead to complications, specifically
skin sores or
gangrene.[2]
About 4% of people have the condition.[3] Onset of the primary form is typically between ages 15 and 30 and occurs more frequently in females.[3][4] The secondary form usually affects older people.[4] Both forms are more common in cold
climates.[4]
Signs and symptoms
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 (called
pallor) 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 by
swelling, tingling, and a painful "pins and needles" sensation. All three color changes are observed in classic Raynaud's. However, 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 reactive
hyperemia of the areas deprived of blood flow.
In
pregnancy, this sign normally disappears due to increased surface blood flow. Raynaud's has occurred in breastfeeding mothers, causing nipples to turn white and painful.[8]
Causes
Primary
Raynaud's disease, or primary Raynaud's, is diagnosed if the symptoms are
idiopathic, 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 partly
hereditary, although specific genes have not yet been identified.[9]
Smoking increases 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.[10]
Secondary
Raynaud's phenomenon, or secondary Raynaud's, occurs secondary to a wide variety of other conditions.
Secondary Raynaud's has a number of associations:[11]
Erythromelalgia (clinically presenting as the opposite of Raynaud's, with hot and warm extremities, often co-exists in patients with Raynaud's[15])
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's can precede these other diseases by many years, making it the first presenting symptom. This may be the case in the
CREST 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 with
scleroderma, 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.[16]
Mechanism
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 cold atmosphere. In all cases, the primary cause is an underlying hyperactivation of the
sympathetic nervous system. Although, with different types, the exact pathophysiology differs. In primary type there is increase in sensitivity due to reasons mentioned above resulting in
vasoconstriction. In secondary type, normal activity of blood vessel is disrupted due to the same reasons mentioned above causing vasoconstriction which leads to
ischemia and
tissue death.[17]
Diagnosis
Distinguishing Raynaud's disease (primary Raynaud's) from Raynaud's phenomenon (secondary Raynaud's) is important. Looking for signs of
arthritis or
vasculitis, as well as a number of 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.[18]
If suspected to be secondary to
systemic sclerosis, one tool which may help aid in the prediction of systemic sclerosis is thermography.[19]
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 15
mmHg is diagnostic (positive).
To aid in the diagnosis of Raynaud's phenomenon, multiple sets of diagnostic criteria have been proposed.[20][21][22][23] Table 1 below provides a summary of these various diagnostic criteria.[24]
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.[24]
Management
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) and
sympathomimetic drugs.[25]
Medications
Medications can be helpful for moderate or severe disease.
Vasodilators –
calcium channel blockers, such as the
dihydropyridinesnifedipine or
amlodipine, preferably slow-release preparations – are often first-line treatment.[25] They have the common side effects of headache, flushing, and ankle
edema, but these are not typically of sufficient severity to require cessation of treatment.[26] The limited evidence available shows that calcium-channel blockers are only slightly effective in reducing how often the attacks happen.[27] Although, other studies also reveal that CCBs may be effective at decreasing severity of attacks, pain and disability associated with Raynaud's phenomenon.[28] People whose disease is secondary to
erythromelalgia 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.[25]
Statins have a protective effect on blood vessels, and
SSRIs such as
fluoxetine may help symptoms, but the data is weak.[25]
PDE5 inhibitors, such as
sildenafil and
tadalafil, 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.[33]
Surgery
In severe cases, an
endoscopic thoracic sympathectomy procedure can be performed.[34] 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 of
botulinum toxin. The 2009 article[35] 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[36] 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.[37]
^
abcd"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. Retrieved 1 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. Retrieved 1 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, retrieved 15 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.
^Linnemann B, Erbe M (2016). "Raynaud's phenomenon and digital ischaemia – pharmacologic approach and alternative treatment options". VASA. 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.