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Health Protocols

Raynaud's Phenomenon

Diagnosis and Conventional Treatment


Raynaud’s phenomenon can be a difficult condition to diagnose because it has a complex set of causes, which may act by various different mechanisms, and signs and symptoms can vary. The primary goal of diagnosis is to determine if any underlying medical condition is contributing to the clinical signs and symptoms, as this allows the physician to distinguish primary from secondary Raynaud’s phenomenon (Baumhakel 2010).

Primary Raynaud’s phenomenon is diagnosed based on several criteria (Stewart 2012):

  • A history of attacks, triggered by cold or stress, involving both hands. Keeping a diary of the attacks and taking photographs of the affected areas are helpful. History also can reveal factors, such as drugs or activities (eg, smoking) that initiate or aggravate the attacks (Goundry 2012). Clinicians may also conduct an “ice test,” in which the patient’s hands are submerged in ice or ice water to observe any color changes (Delp 1986).
  • Lack of necrosis (tissue death) or other signs of tissue damage.
  • No history of physical signs or symptoms of any underlying condition.
  • Normal blood vessels in the nail fold, the area around the nail, based on capillaroscopy. Capillaroscopy is a noninvasive test in which the physician examines the nail fold under a special microscope. A positive test (eg, giant capillaries and tiny hemorrhages) rules out primary Raynaud’s in favor of secondary Raynaud’s, and may be a sign of early systemic sclerosis (Herrick 2012; Cutolo 2008). After Raynaud’s phenomenon is diagnosed, follow-up capillaroscopy is suggested approximately every 6 months (Cutolo 2008).

Diagnostic lab tests include complete blood count, erythrocyte sedimentation rate (ESR), and anti-nuclear antibody screening (ANA). The physician may also assess thyroid hormone levels and perform an X-ray to confirm there is no cervical rib, a condition in which an extra rib sometimes develops in conjunction with a vertebra in the neck. This can affect blood flow, especially to the arms (Herrick 2012).

Some specialists use an imaging technique called thermography. In this approach, the reaction of the fingers to a moderately cold temperature exposure is monitored using specialized equipment designed to assess temperature change. This test is expensive and rarely used in the primary care setting (Ammer 1996; Herrick 2012).

Additional tests are conducted to differentiate secondary from primary Raynaud’s phenomenon (Herrick 2012):

  • Autoantibody levels that might signify the presence of an underlying autoimmune disease. Autoantibodies can cause the immune system to attack the body’s own tissue.
  • Arterial Doppler and/or large vessel imaging if atherosclerosis in the large arteries is suspected.
  • Dermatoscopy or ophthalmoscopy, in addition to capillaroscopy, to identify capillary abnormalities.

The presence of ulcerations of the fingers or toes is usually a sign of secondary Raynaud’s phenomenon, and suggests the cause (eg, an existing connective tissue disorder) has to be examined (Goundry 2012).

Conventional Treatment

Primary Raynaud’s phenomenon. Most people with primary Raynaud’s phenomenon can be treated conservatively with lifestyle approaches. (Baumhakel 2010). Important lifestyle considerations include:

  • Dressing warmly, in layers (Mayo Clinic 2011c).
  • Keeping the extremities warm (wearing warm socks, gloves, or mittens) (Mayo Clinic 2011c).
  • Avoiding touching anything that vibrates (Stewart 2012).
  • Quitting smoking, since smoking is a well-known vasoconstrictor (Levien 2010).
  • Avoiding caffeine, which is a vasoconstrictor (Levien 2010).  
  • Avoiding emotional stress (Levien 2010).

However, if symptoms are frequent and last for a long time, medication may be needed (see Table 1). Most drugs used to treat primary and secondary Raynaud’s phenomenon either promote vasodilation or suppress vasoconstriction. Although several drugs have been investigated, few are approved by the Food and Drug Administration (FDA) for the treatment of Raynaud’s phenomenon (Stewart 2012; Levien 2010).

Calcium channel blockers are typically the first line of treatment for primary Raynaud’s, and of these, nifedipine (eg, Adalat®, Afeditab®, Procardia®) has been the most widely used (Herrick 2011, 2012).

Secondary Raynaud’s phenomenon. The most important approach in the management of secondary Raynaud’s phenomenon is to treat the underlying condition (Herrick 2011). Patients also need to follow the same lifestyle approaches as those with primary Raynaud’s, and calcium channel blockers are also the first-line medical treatment for the Raynaud’s symptoms. However, individuals with secondary Raynaud’s phenomenon who do not respond to calcium channel blockers may need other medications, which are listed in Table 1 and described below (Baumhakel 2010).

Patients with ulcers, necrosis, or gangrene may be hospitalized and receive intravenous prostaglandins and/or phosphodiesterase-5 (PDE-5) inhibitors. Those with underlying systemic sclerosis may also be treated with the dual endothelin receptor antagonist bosentan (Tracleer®) to prevent the development of new ulcers (Baumhakel 2010). Bosentan is approved to treat pulmonary arterial hypertension (Gabbay 2007). It works by interfering with the interaction between the protein endothelin-1 and cellular receptors. The binding between these two causes vasoconstriction, and interfering with this process prevents it (Clozel 1994; Channick 2001).

Calcium channel blockers (CCB). These drugs represent the first-line treatment for primary and secondary uncomplicated Raynaud’s phenomenon that does not respond to lifestyle changes; nifedipine (eg, Procardia®) is a commonly used and well-studied drug in this class (Lambova 2009; Herrick 2011, 2012). An important aspect of the treatment is to start with the lowest dose, and then gradually increase it until symptoms improve. Extended-release formulations often cause fewer side effects and are usually well tolerated (Herrick 2012). A comprehensive review of 18 randomized, placebo-controlled, double-blind trials of calcium channel blockers in patients with primary Raynaud’s phenomenon found these drugs led to significant reductions in severity (approximately 33% reduction) and frequency of attacks (Thompson 2005).

Phosphodiesterase-5 (PDE-5) inhibitors. These drugs work, in part, by enhancing nitric oxide-dependent vasodilation. Studies on their efficacy are mixed, and they are usually used when other vasodilator drugs are not effective (Herrick 2012). One small study of sildenafil (Viagra®) in patients with systemic sclerosis reported that the drug improved blood flow to the fingers, with maximum benefit being reached after a few months of treatment; it also helped heal ulcers on the fingers. However, during the study, many participants developed new ulcers while receiving treatment, indicating that the drug does not prevent new ulcers from forming (Herrick 2012; Brueckner 2010).

Two new PDE5 inhibitors are being studied for Raynaud’s phenomenon. Udenafil (Zydena®) is a newer PDE5 inhibitor that is more selective for PDE5 than previous compounds, which inhibit other types of phosphodiesterases as well (Paick 2008; Sung 2012). A clinical trial that analyzed 52 participants compared udenafil with the calcium channel blocker amlodipine (Norvasc®) for the treatment of secondary Raynaud’s phenomenon; no differences in the mean number of attacks per day between the 2 groups were observed ( (a) 2012). Another clinical trial, evaluating the investigational compound PF-00489791, was completed in 2011, but no results were available as of early 2013 ( (b) 2012).

Angiotensin-converting enzyme (ACE) inhibitors. A comprehensive review of 3 studies on the effectiveness of captopril (Capoten®) or enalapril (Vasotec®) compared to placebo in patients with primary Raynaud’s phenomenon found non-significant differences between captopril and placebo on the average number of attacks per week and a small increase in the frequency of attacks with enalapril (Stewart 2012). Nonetheless, the drugs are still prescribed sometimes since individual patients may receive some benefit.

Angiotensin II receptor antagonists. These drugs are sometimes used alone or in addition with calcium channel blockers to treat Raynaud’s phenomenon. However, there is little evidence to support their effectiveness, and these drugs may be less effective in patients with Raynaud’s secondary to scleroderma than in those with the primary form of the disease (Gliddon 2007; Herrick 2012).

Serotonin reuptake inhibitors. Serotonin acts as a vasoconstrictor and enhances blood clotting; therefore, serotonin reuptake inhibitors have the potential to ease Raynaud’s symptoms in some patients (Herrick 2012). Much of the evidence for their use stems from case studies or very small clinical studies, primarily with fluoxetine (Prozac®). A study that enrolled 26 patients with primary Raynaud’s phenomenon and 27 patients with secondary Raynaud’s phenomenon compared 6-week treatments with fluoxetine and nifedipine, and reported a decreased frequency and severity of the attacks in both treatment groups, but statistical significance was seen only for patients treated with fluoxetine. Additionally, comparisons among subgroups of patients revealed that women and those with primary Raynaud’s phenomenon showed the best response (Coleiro 2001). Importantly, some studies reported that symptoms get worse with serotonin reuptake inhibitors, while others reported that the effects are not different than what can be observed with placebo (Lambova 2009; Levien 2010).

Statins. Several studies suggest that statin therapy for patients with Raynaud’s phenomenon secondary to systemic sclerosis can reduce the number of new ulcers on the fingers or toes. Statins have several effects, which include suppressing inflammation, improving blood vessel function, and inhibiting smooth muscle proliferation, all of which can reduce damage to the lining of blood vessels associated with Raynaud’s phenomenon. Some studies showed that statins can delay vascular damage, but insufficient evidence exists to recommend them as a standard drug (Kuwana 2006; Abou-Raya 2008; Herrick 2012).

Prostacyclins. Intravenous infusion of the prostacylins epoprostenol (Flolan®, Veletri®), treprostinil (Remodulin®), and iloprost is a treatment of choice in patients with severe secondary Raynaud’s phenomenon who develop ulcers on their fingers or toes. Studies found that these medications reduce the severity and frequency of Raynaud’s phenomenon attacks and help the healing of finger and toe ulcers, while iloprost also decreases the inflammation associated with the disease. Although there is an oral form of iloprost, studies are mixed regarding its effectiveness (Lambova 2009). A study presented at the 2011 annual meeting of the American College of Rheumatology/ Association of Rheumatology Health Professionals found that the oral prostacyclin treprostinil diethanolamine, which is a salt form of the prostacyclin analog treprostinil, improved the patients’ perception of their change in hand ulcerations and of the Raynaud’s phenomenon symptoms (Selbold 2011). This drug is investigational only as of the time of this writing.

Individuals with ulceration of their fingers or toes due to lack of blood flow require immediate medical attention. These patients are typically treated with intravenous prostaglandin therapy, pain medication, and antibiotics. Patients may also receive antiplatelet and anticoagulant therapies, despite the lack of evidence for their efficacy. Endothelin-1 receptor antagonists such as bosentan may also be used to suppress vasoconstriction. Two clinical trials of bosentan found the drug reduced the number of new finger or toe ulcers, but it did not heal existing ulcers (Herrick 2012).

Table 1:  Medications Used to Treat Raynaud’s Phenomenon

(Sources: Stewart 2012; Baumhakel 2010, unless otherwise noted)


Generic/Brand Name

Potential Side Effects

Vasodilator antihypertensive drugs, including prostacyclin analogues

Bosentan (Tracleer®), hydralazine (Apresoline®), iloprost

Headache, flushing, itching, runny nose, sore throat, other cold symptoms, heartburn (Medline Plus 2010)

Alpha-adrenergic blockers

Doxazosin (Cardura®), indoramin, prazosin (Minipress®), terazosin (Hytrin®)

Low blood pressure, dizziness, headache, pounding heartbeat, nausea, weakness, weight gain, changes in blood cholesterol (Mayo Clinic 2010a).

Angiotensin-converting enzyme (ACE) inhibitors

Captopril (Capoten®), cilazapril, enalapril (Vasotec®), fosinopril (Monopril®), lisinopril (Prinivil®, Zestril®), moexipril (Univasc®), perindopril (Aceon®), quinapril (Accupril®), ramipril (Altace®), trandolapril (Mavik®)

Dry cough, increased blood-potassium level (hyperkalemia), fatigue, rash, dizziness, headaches, sleep problems, rapid heartbeat (Mayo Clinic 2010b)

Angiotensin-II receptor antagonists

Candesartan (Atacand®), eprosartan (Teveten®), losartan (Cozaar®), olmesartan (Benicar®), telmisartan (Micardis®), valsartan (Diovan®)

Headache, dizziness, lightheadedness, nasal congestion, back and leg pain, diarrhea (Mayo Clinic 2011a)

Calcium channel blockers

Nifedipine (Adalat®, Afeditab®, Procardia®), amlodipine (Norvasc®), felodipine (Plendil®)

Constipation, headache, rapid heartbeat, dizziness, rash, drowsiness, flushing, nausea, swelling of the feet and lower legs (Mayo Clinic 2010c)


Glyceryl trinitrate, isosorbide dinitrate, isosorbide mononitrate

Headache, dizziness, skin irritation (Chung 2009)

Peripheral vasodilators and related drugs

Cilostazol (Pletal®), pentoxifylline (Pentoxil®, Pentopak®, Trental®)

Fever, fast or irregular heartbeat,  chest pain, abnormal bleeding (rarely), stomach pain  (less common) (Mayo Clinic 2011b; Mayo Clinic 2012a)

Serotonin reuptake inhibitors

Citalopram (Celexa®), escitalopram (Lexapro®), fluoxetine (Prozac®), fluvoxamine (Luvox®), paroxetine (Paxil®, Pexeva®), sertraline (Zoloft®)

Nausea, drowsiness, dry mouth, rash, headache, diarrhea, nervousness, agitation or restlessness, insomnia, reduced sexual desire or difficulty reaching orgasm, inability to maintain an erection (erectile dysfunction), increased sweating, weight gain  (Mayo Clinic 2010d)

Phosphodiesterase type-5 inhibitors

Sildenafil (Viagra®), tadalafil (Cialis®), vardenafil (Levitra®, Staxyn®)

Indigestion, heartburn, runny nose, muscle aches and stiffness (with Cialis®), headache, temporary vision changes (including blurred vision), cold sweats (with Viagra® and Levitra®) (Mayo Clinic 2012b; Mayo Clinic 2012c; Mayo Clinic 2012d)


Atorvastatin (Lipitor®)

Headache, hoarseness, pain or tenderness around the eyes and cheekbones, lower back or side pain, painful or difficult urination, stuffy or runny nose (Mayo Clinic 2012e)