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Raynaud’s Phenomenon

Raynaud’s phenomenon (RP) was first described in 1862 by Maurice Raynaud. It is thought to be related to a complex connection of inappropriate vascular constriction of the digital arteries and arterioles, alpha-2 adrenergic response involving the sympathetic nervous system, nitric oxide, and endothelial cells production of endothelin-1.

RP is considered primary when there is no associated disease or contributing condition, and secondary when there is an associated disease (most commonly connective tissue disease, such as scleroderma, systemic lupus erythematosus, mixed connective tissue disease), environmental exposure, or  medication.

Clinical Manifestations

RP is associated with reversible vasoconstriction typically secondary to a decrease in temperature or increased emotional stress.  Attacks present acutely with the association of pallor, progressing to cyanosis and then erythema on warming. The duration of attacks varies depending on the associated conditions. The digits are most commonly affected, but other peripheral anatomy has also been described (ears and nose).

On vasoconstriction, there may be additional superficial cutaneous changes with collateral circulation resulting in a lacelike reticular pattern referred to as livedo reticularis.

There is no gold standard in the diagnosis of RP. Careful history and physical exam are generally all that are needed for diagnosis. Physical exam may include capillary loop microscopy, which on the nail bed, can be performed with an ophthalmoscope and oil magnification on 40 diopters. An abnormal nail bed capillary loop microscopy shows such features as dilated capillary loops along with capillary loop dropout  resulting in areas of loss in normal capillary perfusion.  These findings are typically seen in secondary RP.


RP generally has its onset in the second through fourth decade, and it is more common in women and in family members of affected individuals. The diagnosis is typically made through patient history involving vasoconstriction with two of the three color changes noted above, pallor being the most significant of the three. Prevalence is poorly defined and ranges in different populations from as low as 3% to as high as 19%.


RP is a complex of inappropriate vascular constriction of the digital arteries and arterioles thought to involve alpha-2 adrenergic response by the sympathetic nervous system, nitric oxide (NO), and endothelial cells production of endothelin-1.

The sympathetic nervous system regulates vasoconstriction of arteries and arterioles. Norepinephrine acts as a vasoconstrictor on alpha-2 adrenergic receptors located on vascular endothelium. The inhibition of alpha-2 adrenergic response by yohimbine and subsequent vasodilation, illustrates the role of alpha-2 adrenergic receptors in this process. Endothelial cells produce endothelin-1, which is a vasoconstrictor. Activation of platelets produces vasoactive effects through thromboxane and serotonin.

Endothelial cells also release nitric oxide, which is involved in vascular smooth muscle relaxation. Nitric oxide has a role in inhibition of platelet aggregation as well. Endothelial cells are responsible for vasodilation with the release of prostacyclin. 


RP generally presents as a symmetric episodic vasoconstriction response of the digits to low temperatures or increased emotional stress. This is typically seen as presentation of pallor, then cyanosis and erythema upon vasodilation and rewarming. Duration of episodes is variable depending on environmental exposure, underlying disease associations, and medication.

RP that is not associated with extreme or repetitive environmental exposures, medication, or disease does not typically progress to anoxia and necrosis/gangrene. 

A new presentation of RP should prompt evaluation for associated environmental exposure, medication or disease process.

Disease and medication associations for RP include:

  • Frost bite
  • Vibration injury
  • Sympathomimetics
  • Inferferon
  • Nicotine
  • Cocaine
  • Ergotamines
  • Caffeine
  • Scleroderma
  • Systemic lupus erythematosus
  • Sjogren's syndrome
  • Mixed connective tissue disease
  • Paraneoplastic
  • Cryoglobulinemia
  • Cryofibrinogenemia

Radiographic and laboratory findings

After a careful history and physical exam, there may be further need for a laboratory workup for RP. All patients with RP should have laboratory evaluation to discern secondary RP. The basic evaluation will require complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and antinuclear antibodies (ANA) to discern secondary causes. Additional workup can be directed on a case-by-case basis.

There are no clinically available radiographic evaluations for RP.

Risk factors and prevention

RP episodes may be decreased by conservative measures. The degree of benefit will vary depending on patient and associated conditions. 

Avoidance of cold and damp exposure is essential. Keeping the affected area dry will also decrease heat loss. During colder weather, the use of mittens instead of gloves will promote digit warming. The use of wool socks, instead of cotton, will decrease moisture retention and may better preserve warmth. It is also advisable to promote core (chest) temperature warmth by dressing in multiple layers to trap heat. Heat loss of the core may result in peripheral vasoconstriction to increase blood flow to the core.  In addition, it should be remembered that considerable heat loss may occur through the scalp and keeping the head covered can help reduce symptoms as well.

Avoid nicotine and caffeine, which may help prevent peripheral vasoconstriction.

Treatment options

Medications used to treat RP include the following:

  • Calcium channel blockers
  • Vasodilators
  • Phosphodiesterase inhibitors
  • Sympatholytic agents
  • Prostaglandins
  • Aspirin
  • Surgical treatment

Calcium channel blockers are considered the first line treatment for patients who have failed conservation non-medication treatment.  Medications in this class are thought to induce vasodilation though inhibition of voltage gated calcium channels associated with vascular smooth muscle.  The dihydropyridine calcium channel blockers are the most commonly used medications (nifedipine, amlodipine, felodipine) due to a more selective effect on peripheral vasculature.

Nitroglycerine, nitroprusside, hydralazine and minoxidil have a direct potent dilatory effect.  Nitroglycerin ointment can be applied directly to the affected area, ie, the digits, but can cause rebound vasocontriction when removed.

Selective serotonin reuptake inhibitor (SSRI) fluoxetine may help with reduction of platelet aggregation similar to aspirin.

Bosentan, an endothelin receptor inhibitor, approved for the treatment of pulmonary hypertension (PAH), may decrease the frequency of Raynaud's when used in the treatment of PAH.
Sildenafil and tadalafil, used in the treatment of PAH, act through inhibition of phosphodiesterase type 5 and could promote vasodilation through nitric oxide.

The sympatholytic agent prazosin acts to inhibit alpha adrenergic receptors and causes vasodilation.

Prostaglandins E1, prostacyclin and iloprost are administered parenterally and should be considered for ischemic digits when other preparations have failed.

Surgical options are of last resort and involve sympathectomy.



Holistic medicine




Key terms

Raynaud’s, Raynaud’s phenomenon, scleroderma, systemic lupus erythematosus SLE, lupus

Skills and competencies

Understand that vasoconstriction of vasculature in Raynaud's involves the sympathetic nervous system and biochemical mediators.

Understand the difference between primary and secondary Raynaud's Phenomenon.

Know the disease and medication associations.

Conservative (non-medication) and medication treatment.


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