Approach Considerations
General measures for Raynaud phenomenon include education, warming of the affected body part, and cessation of vasoconstricting agents such as nicotine. A number of pharmacologic treatments have been studied, but none provide a cure and none has been approved for this indication in the United States. In an international study of patients with self-reported Raynaud phenomenon, 82% reported that at least one currently used medication was tolerated, but only 16% reported that at least one current medication was effective. [37]
For primary Raynaud phenomenon, the first line of therapy consists of lifestyle measures, such as avoidance of precipitating factors and use of gloves. [38] If these prove inadequate, the patient may be considered for calcium channel blocker treatment; nifedipine is the usual choice. Topical nitroglycerin (1% or 2%) has been found to help if applied locally. [39, 40]
Therapy for secondary Raynaud phenomenon must be tailored to the underlying disorder. If the disorder is associated with occupational or toxic exposure, the patient should avoid the inciting environment.
Patients with hyperviscosity syndromes and cryoglobulinemia improve with treatments that decrease the viscosity and improve the rheologic properties of their blood (eg, plasmapheresis). Unfortunately, patients with Raynaud phenomenon associated with autoimmune disorders do not usually respond well to therapy. Hepatitis B, hepatitis C, and Mycoplasma infections need to be addressed, if present.
Patients with secondary Raynaud phenomenon should also use lifestyle measures. However, these patients are more likely to require pharmacologic therapy than are patients with primary Raynaud phenomenon.
Pharmacologic options for secondary Raynaud phenomenon include calcium channel blockers and prostacyclin analogues. Other agents may be considered; however, in a meta-analysis of interventions for secondary Raynaud phenomenon by Huisstede et al, solid evidence for therapies beyond calcium channel blockers and the prostacyclin analogue iloprost was lacking. [41]
Nonpharmacologic Therapy
Nondrug therapy may be all that is required for mild cases of primary Raynaud phenomenon. With time, most patients learn to incorporate these therapies on their own. Such therapies can include the following:
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Avoiding inciting environmental factors, such as direct contact with frozen foods or cold drinks
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Insulation against cold and local warming, including gloves or heavy socks and electric and chemical warming devices
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Discontinuing drugs that may provoke vasospasm
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Avoiding smoking [42]
Laser therapy may result in less frequent, less severe attacks. However, this therapy needs more study. [43]
Studies of acupuncture have been limited, but have suggested some benefit. [44] Biofeedback and relaxation have shown no difference in frequency or severity of attacks. [43, 45]
Herbal remedies that have shown some benefit in Raynaud phenomenon include evening primrose oil (which contains gamma linolenic acid, a precursor of prostaglandin E) [46, 47] and Ginkgo biloba extract. [48, 49]
Physical maneuvers for alleviating acute attacks that involve the hands have been proposed. In the so-called windmill maneuver, the affected person rotates the arms backward, in a motion similar to a softball pitcher; the resulting centrifugal force enhances blood flow through the distal arteries. More recently, a "Frisbee" maneuver has been suggested for patients unable or reluctant to perform the windmill maneuver. This maneuver begins with the forearm flexed at a 90-dgree angle and internally rotated across the chest. The patient then rotates the forearm laterally, in a snapping motion, while maintaining digital extension, and repeats this movement rapidly. [50]
Pharmacologic Therapy
Calcium channel blockers are the class of drugs most widely used for treatment of Raynaud syndrome—especially the dihydropyridines (eg, nifedipine, nicardipine), which are the most potent vasodilators. [51] Nifedipine is the customary first choice. The usual dosage is 30-120 mg of the extended-release formulation taken once daily. Start with the lowest dose and titrate up as tolerated. If adverse effects occur, decrease the dosage or use another agent, such as nicardipine, or a non-dihydropyridine calcium channel blocker such as such as diltiazem.
Patients should check their blood pressure regularly and may want to keep a log of the number and severity of attacks. This may help in evaluating the efficacy of therapeutic management.
Topical calcium channel blockers promote healing of digital ulcers in these patients. [52] However, topical preparations have to be compounded by the pharmacist.
Other medications that have been studied in Raynaud phenomenon include the following [53] :
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Topical nitroglycerin (1% or 2%) [39]
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Iloprost (prostaglandin analog) [54]
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Selective serotonin reuptake inhibitors (SSRIs)
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Phosphodiesterase-5 enzyme inhibitors (sildenafil, tadalafil, vardenafil) [55]
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Losartan [56]
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Bosentan (endothelin receptor antagonist) – Orphan drug for treating new digital ulcers in patients with systemic sclerosis [54]
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N-acetylcysteine – In patients with systemic sclerosis and digital ulcers
Topical nitroglycerin (1% or 2%) has been found to help if applied locally. [39, 40] Side effects include headache and dizziness.
Improvement in Raynaud phenomenon has been reported in patients treated with the SSRIs fluoxetine, sertraline, and escitalopram. However, exacerbation of Raynaud phenomenon has also been reported with SSRI treatment. [53]
Botulinum toxin injection, typically in the vicinity of the palmar digital neurovascular bundle, has been used in both primary and secondary Raynaud syndrome. [62] Improvement in symptoms and healing of digital ulcers has been reported. [57, 58, 59, 60, 61] In one study, some patients derived long-term benefit from a single treatment, whereas in patients with systemic sclerosis, repeat treatments were administered after an average of 6 months. [60]
Therapy with antiplatelet agents has been attempted but has not been proved effective. [63] A randomized controlled trial by Gliddon et al showed no significant difference in attack frequency or severity between the angiotensin-converting enzyme inhibitor quinapril and placebo. [64] High-quality, well-designed, randomized controlled trials are needed to study the effect of other pharmacotherapy. Anticoagulation is not indicated, except in rare cases of rapidly advancing digital ischemia.
Treatment of Critical Digital Ischemia
Critical digital ischemia, which is more likely to occur in secondary Raynaud phenomenon, necessitates aggressive management. It is considered a medical emergency that requires hospitalization. Warm temperature and bed rest are used to decrease trauma and activity and to control pain. Local infiltration of lidocaine or bupivacaine at the base of the involved digits decreases sympathomimetic input, reduces ischemic pain, and improves blood flow.
In patients with rapidly advancing ischemia, anticoagulant therapy may be necessary. No algorithms or studies exist for the use of heparin. Intravenous iloprost, alprostadil, or epoprostenol can be used if anticoagulant therapy fails or if the ischemia rapidly worsens. Failure of all these therapies might warrant surgical intervention with distal digital sympathectomy and arterial reconstruction. [65]
While treatment is proceeding, further workup for underlying conditions must be performed. Conditions to consider include vasculitis, thrombosis, and atherosclerosis.
Consultations
Typically, primary Raynaud phenomenon does not require any consultations. Secondary Raynaud phenomenon may require consultation with a rheumatologist or hematologist to delineate associated syndromes.
Fixed (nonreversible) lesions are not Raynaud phenomenon. These patients may require referral to a rheumatologist, vascular surgeon, orthopedist, or other specialist.
Diet
Fish oils containing omega-3-fatty acids may be beneficial in some patients with primary Raynaud phenomenon; however, this has not been validated in high-quality studies. A single study found improved tolerance to cold exposure and delayed onset of vasospasm in five of 11 patients with primary Raynaud phenomenon; the dosage used was 12 fish-oil capsules daily. [66] Antioxidant supplementation has not been shown to produce clinical improvement. [43]
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A 9-year-old with Raynaud phenomenon. Notice the discoloration of the fingers.
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Photo of a patient with Raynaud phenomenon that resulted from working with a jackhammer. Courtesy of the CDC.
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Raynaud phenomenon showing demarcation of color difference.
