Overall prevalence is approximately 3 to 5%; women are affected more than men, and younger people are affected more than older people (1, 2). Raynaud phenomenon is probably due to an exaggerated alpha-2 adrenergic response that triggers vasospasm; the mechanism is not defined.
Primary Raynaud phenomenon (also called Raynaud disease) is much more common (80 to 90% of cases) than secondary; it occurs without symptoms or signs of other disorders (3, 4). In the remaining 10 to 20% of patients with Raynaud symptoms, a causative underlying disease (eg, systemic sclerosis) will be evident at initial presentation or diagnosed subsequently.
Secondary Raynaud phenomenon (also called Raynaud syndrome) accompanies various disorders and conditions, mostly systemic rheumatic diseases (see table Causes of Secondary Raynaud Phenomenon).
Causes of Secondary Raynaud Phenomenon
Cause | Examples |
|---|---|
Systemic rheumatic diseases | Mixed or undifferentiated connective tissue disease Idiopathic inflammatory myopathies (eg, polymyositis, dermatomyositis) |
Endocrine disorders | |
Hematologic disorders | |
Neoplastic disorders | |
Neurologic disorders | |
Trauma | Vibration |
Vascular disorders | |
Medications and substances | Beta-blockers Cocaine Ergot preparations Nicotine Sympathomimetic medications |
Nicotine commonly contributes to secondary Raynaud phenomenon but is often overlooked. Raynaud phenomenon may accompany migraine headaches, variant angina, and pulmonary hypertension, suggesting that these disorders share a common vasospastic mechanism.
General references
1. Garner R, Kumari R, Lanyon P, Doherty M, Zhang W. Prevalence, risk factors and associations of primary Raynaud's phenomenon: systematic review and meta-analysis of observational studies. BMJ Open 2015;5(3):e006389. doi:10.1136/bmjopen-2014-006389
2. Wigley FM, Flavahan NA. Raynaud's Phenomenon. N Engl J Med 2016;375(6):556-565. doi:10.1056/NEJMra1507638
3. Klein-Weigel P, Sander O, Reinhold S, Nielitz J, Steindl J, Richter J. Raynaud's Phenomenon: A Vascular Acrosyndrome That Requires Long-Term Care. Dtsch Arztebl Int Published online April 9, 2021. doi:10.3238/arztebl.m2021.0023
4. Shenavandeh S, Ajri M, Hamidi S. Causes of Raynaud's phenomenon and the predictive laboratory and capillaroscopy features for the evolution to a definite connective tissue disease. Rheumatology (Oxford) 2022;61(5):1975-1985. doi:10.1093/rheumatology/keab668
Symptoms and Signs of Raynaud Phenomenon
Sensations of coldness, burning pain, paresthesias, or intermittent color changes of one or more digits are precipitated by exposure to cold, emotional stress, or vibration. All can be reversed by removing the stimulus. Rewarming the hands accelerates restoration of normal color and sensation.
Color changes are clearly demarcated across the digit. They may be triphasic (pallor, followed by cyanosis and after warming by erythema due to reactive hyperemia), biphasic (cyanosis, erythema), or uniphasic (pallor or cyanosis only). Changes are often symmetric. Raynaud phenomenon does not occur proximal to the metacarpophalangeal joints; it most commonly affects the middle 3 fingers and rarely affects the thumb. Vasospasm may last minutes to hours but is rarely severe enough to cause tissue loss in primary Raynaud phenomenon.
Raynaud phenomenon secondary to a systemic rheumatic disease may progress to painful digital gangrene; Raynaud phenomenon secondary to systemic sclerosis tends to cause extremely painful, infected ulcers on the fingertips.
Multiple fingertips are cyanotic.
© Springer Science+Business Media
Pallor develops irregularly in the fingers.
© Springer Science+Business Media
Ulceration and gangrene affect the second finger in this patient who had Raynaud phenomenon secondary to systemic sclerosis.
© Springer Science+Business Media
Multiple fingertips are cyanotic.
© Springer Science+Business Media
Pallor develops irregularly in the fingers.
© Springer Science+Business Media
Ulceration and gangrene affect the second finger in this patient who had Raynaud phenomenon secondary to systemic sclerosis.
© Springer Science+Business Media
Diagnosis of Raynaud Phenomenon
History and physical examination
Evaluation and testing for underlying disorder
Sometimes Doppler ultrasound and laboratory testing
Diagnostic criteria for Raynaud phenomenon are based upon a history of unusual cold sensitivity, biphasic color changes involving white and blue digits (pallor or duskiness in patients with dark-skin), and additional history and examination-based elements (1). Acrocyanosis also causes color change of the digits in response to cold but differs from Raynaud phenomenon in that it is persistent, not easily reversed, and does not cause trophic changes (thin, shiny, or discolored skin; hair loss; brittle nails), ulcers, or pain.
Primary and secondary forms are distinguished clinically, supported by vascular laboratory studies and blood testing.
Clinical findings
A thorough history and physical examination directed at identifying a causative disorder are helpful but rarely diagnostic.
Findings suggesting primary Raynaud phenomenon are the following (1):
Age at onset < 40 years (in two-thirds of cases)
Mild symmetric attacks affecting both hands
No tissue necrosis or gangrene
Negative or low (< 1:40) antinuclear antibody (ANA) titer
No history or physical findings suggesting another cause
Findings suggesting secondary Raynaud phenomenon are the following:
Age at onset > 40 years
Severe painful attacks that may be asymmetric and unilateral
Ischemic lesions
History and findings suggesting an accompanying disorder
Laboratory testing
Vascular laboratory testing includes measuring digital pulse wave forms and pressures.
The main blood tests are to diagnose autoimmune or inflammatory diseases (eg, measurement of erythrocyte sedimentation rate [ESR] or C-reactive protein, antinuclear and anti-DNA antibodies, rheumatoid factor, anticentromere antibody, anti-cyclic citrullinated peptide [CCP] antibodies, anti-scleroderma [SCL] 70 antibody) .
Diagnosis reference
1. Klein-Weigel P, Sander O, Reinhold S, Nielitz J, Steindl J, Richter J. Raynaud's Phenomenon: A Vascular Acrosyndrome That Requires Long-Term Care. Dtsch Arztebl Int Published online April 9, 2021. doi:10.3238/arztebl.m2021.0023
Treatment of Raynaud Phenomenon
Trigger avoidance
Smoking cessation
Calcium channel blockers or other medications
Treatment of primary Raynaud phenomenon involves avoidance of cold, smoking cessation, and, if stress is a triggering factor, relaxation techniques (eg, biofeedback) or counseling (1, 2). Medications are used more often than behavioral treatments because of convenience. Vasodilating long-acting dihydropyridine calcium channel blockers (eg, extended-release nifedipine, amlodipine, felodipine, or isradipine ) are most effective and typically used as first-line agents. For patients who do not tolerate calcium channel blockers, alternative agents include topical nitrates, oral phosphodiesterase-5 inhibitors (eg, sildenafil), ). Medications are used more often than behavioral treatments because of convenience. Vasodilating long-acting dihydropyridine calcium channel blockers (eg, extended-release nifedipine, amlodipine, felodipine, or isradipine ) are most effective and typically used as first-line agents. For patients who do not tolerate calcium channel blockers, alternative agents include topical nitrates, oral phosphodiesterase-5 inhibitors (eg, sildenafil),angiotensin II receptor blockers, and selective serotonin reuptake inhibitors (eg, fluoxetine). Beta-blockers, clonidine, and ergot preparations are contraindicated because they cause vasoconstriction and may trigger or worsen symptoms.receptor blockers, and selective serotonin reuptake inhibitors (eg, fluoxetine). Beta-blockers, clonidine, and ergot preparations are contraindicated because they cause vasoconstriction and may trigger or worsen symptoms.
Treatment of secondary Raynaud phenomenon focuses on the underlying disorder. Calcium channel blockers and other medications are given as above for primary Raynaud phenomenon. Antibiotics, analgesics, and, occasionally, surgical debridement may be necessary for ischemic ulcers. Low-dose aspirin may prevent thrombosis but theoretically may worsen vasospasm via prostaglandin inhibition. IV prostaglandins (alprostadil, epoprostenol, iloprost) appear to be effective and may be an option for patients with severely ischemic digits. These medications often require administration in the inpatient setting but may be provided in an experienced outpatient center with appropriate monitoring.may prevent thrombosis but theoretically may worsen vasospasm via prostaglandin inhibition. IV prostaglandins (alprostadil, epoprostenol, iloprost) appear to be effective and may be an option for patients with severely ischemic digits. These medications often require administration in the inpatient setting but may be provided in an experienced outpatient center with appropriate monitoring.
Cervical or local sympathectomy is controversial; it is reserved for patients with progressive disability unresponsive to all other measures, including treatment of underlying disorders. Sympathectomy often abolishes the symptoms, but relief may be temporary.
Treatment references
1. Curtiss P, Svigos K, Schwager Z, Lo Sicco K, Franks AG Jr. Part II: The treatment of primary and secondary Raynaud's phenomenon. J Am Acad Dermatol 2024;90(2):237-248. doi:10.1016/j.jaad.2022.05.067
2. Wigley FM, Flavahan NA. Raynaud's Phenomenon. N Engl J Med 2016;375(6):556-565. doi:10.1056/NEJMra1507638
Key Points
Raynaud phenomenon is reversible vasospasm of parts of the hand in response to cold or emotional stress.
Raynaud phenomenon may be primary or secondary to another disorder, typically a systemic rheumatic disease (eg, systemic sclerosis).
Primary Raynaud phenomenon, unlike the secondary form, rarely causes gangrene or tissue loss.
Diagnose clinically but consider testing to diagnose a suspected cause.
Avoid cold, smoking, and any other triggers.
Give a vasodilating calcium channel blocker or other medications.
Drugs Mentioned In This Article
