Author
Acknowledgment
The information below was prepared
with the help of Daniel Wallace, M.D., Clinical
Professor of Medicine, Cedars-Sinai/UCLA School of Medicine,
Los Angeles, Calif.
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For More Information About
Raynaud's Phenomenon
Visit the excellent Raynaud's
Phenomenon page on the NIAMS/NIH website.
What is Raynaud’s phenomenon?
In 1862, Auguste-Maurice Raynaud in his thesis “Local
asphyxia and symmetrical gangrene of the extremities”
described for the first time color changes of the hands
and feet triggered by exposure to cold temperature.
Today we call this exaggerated response to cold “Raynaud’s
phenomenon” in memory of this French physician.
Raynaud’s phenomenon is defined as episodes of
pallor (white fingers or toes) or cyanosis (blue discoloration)
in response to cold or emotional stimuli. The pallor
is caused by vasoconstriction (narrowing) of blood vessels
(arteries and arterioles ) that results in little blood
to the skin (ischemia), while cyanosis is created by
deoxygenation of slow-flowing blood. After rewarming
the hands, the blood flow will rebound (hyperemia) and
the skin will appear reddened or blushed.
Pallor is the most important physical sign and to make
a diagnosis one should witness a sharply demarcated
area of the finger(s) or toe(s) rather than irregular
mottling. Numbness, tingling, clumsiness of finger use,
and pain can accompany the color changes. It is common
for patients with Raynaud’s phenomenon to complain
of cold sensitivity and to have other areas of the skin
involved including the ears, nose, and knees. Episodes
come as sudden attacks and are most often triggered
by rapid changes in ambient temperature such as walking
into the cold food section of the grocery store. Attacks
may begin in one or two fingers but typically involve
all fingers and/or toes symmetrically and bilaterally.
Primary Raynaud’s phenomenon and, in Europe,
Raynaud’s Disease, are used to denote a patient
without an associated underlying disease. Secondary
Raynaud’s phenomenon is used to describe patients
with a defined secondary or associated disease.
The skin contains a unique system that regulates body
temperature by increasing or decreasing blood flow to
the skin. Cold temperatures increase vascular tone and
decrease skin blood flow to preserve body heat, while
warm temperatures decrease sympathetic tone and increase
cutaneous blood flood allowing loss of body heat. Studies
suggest that in patients with Raynaud’s phenomenon,
the sympathetic receptors (alpha 2C) are overactive
or overexpressed in the smooth muscle of the thermoregulatory
arteries, and thus cause exaggerated responses to cold
temperatures.
Studies also implicate a number of other mechanisms
for causing or aggravating abnormal vascular responses
in individuals with Raynaud’s phenomenon. These
include abnormal release of vasoconstricting molecules
(e.g., endothelin-1) or the underproduction of vasodilators
(e.g., prostacyclin or nitric oxide) from the vessel
itself. Sensory nerves in the skin release small peptides
that can alter blood flow, and the abnormal release
of vasoactive substances from circulating cells can
also occur. An example of the latter would be the release
of serotonin from blood platelets. The regulation of
blood flow in the skin is complex and theoretically
any number of these systems could be altered to cause
Raynaud’s phenomenon.
Who develops Raynaud’s phenomenon?
Surveys done in several different countries find that
about 3% of the general population have symptoms and
signs consistent with Raynaud’s phenomenon. It
is more common among young women and in countries with
cold climates. Most of the individuals with Raynaud’s
phenomenon have uncomplicated primary Raynaud’s
phenomenon without any defined cause or associated systemic
disease. Recent studies find that about 30% of people
with primary Raynaud’s phenomenon have a first-degree
relative with the same condition. This suggests there
is a specific gene associated with Raynaud’s phenomenon
but to date no gene or gene defect has been defined.
There are a number of causes of secondary Raynaud’s
phenomenon. These include diseases that damage blood
vessels, alter the nervous control of blood vessels,
or are associated with abnormal circulating factors.
The most common diseases associated with Raynaud’s
phenomenon are the rheumatic diseases, especially scleroderma,
mixed connective tissue disease, systemic lupus erythematosus,
Sjögren’s syndrome, and dermatomyositis.
Approximately 95% of those diagnosed with systemic scleroderma
have Raynaud’s phenomenon.
Other common causes of Raynaud’s phenomenon include
prolonged use of vibratory tools (e.g., jackhammer operators);
drugs such as sympathomimetic drugs (antihistamines,
ephedrine, epinephrine), ergots (used to treat migraine
headaches), and certain chemotherapeutic agents; peri-pheral
nerve damage such as in carpal tunnel syndrome; and
occlusive vascular disease (such as peripheral arterial
disease) or metabolic diseases, including hypothyroidism.
How do doctors evaluate patients with Raynaud’s
phenomenon?
Raynaud’s phenomenon is a clinical diagnosis
made by a history of cold sensitivity with the associated
typical color changes (white, blue, red) of the skin.
The physician will often witness an attack during the
examination or can use color photos of actual attacks
to help the patient. At this time there is no blood
test that identifies Raynaud’s phenomenon. Cold
challenges (e.g., placing hand in ice water) are not
necessary to make a diagnosis.
Patients presenting to their doctor with a complaint
of Raynaud’s phenomenon should have a complete
history and physical examination to look for any underlying
cause for the attacks. A careful examination of the
blood vessels is important. One special test is nailfold
capillar-oscopy, where a doctor puts a drop of oil on
the patient’s nailfold or the skin at the base
of the fingernail. The physician then examines this
area under a microscope to look for any capillary changes.
Enlarged, dilated, or absent nailfold capillaries are
noted among patients with scleroderma and other rheumatic
diseases.
Blood tests are performed if the history or physical
examination suggests that secondary Raynaud’s
phenomenon is present. The specific testing done depends
on the clinical situation. For example, tests for the
presence of autoantibodies may be done if an autoimmune
disease like scleroderma or systemic lupus erythematosus
is suspected. If vascular disease is suspected, an examination
of larger vessels using arterial Doppler flow studies
may be conducted.
How is Raynaud’s phenomenon treated?
The goals of treatment are to reduce the number and
severity of attacks and to prevent tissue damage. The
mainstay of therapy in all patients with Raynaud’s
phenomenon is avoidance of cold temperature and stress
management. Treatment begins by educating the patient
about the causes of the Raynaud’s attacks, and
methods to avoid the common provoking and aggravating
factors.
Keeping the whole body warm (not just the fingers)
is very important. This is best done by wearing layers
of clothing and covering the head with a hat. Shifting
temperatures and wet, cold, windy days are particularly
associated with worse Raynaud’s events. Contact
with cold objects such as iced beverage containers or
a cold steering wheel should be avoided by covering
these objects or wearing warm gloves. Chemical warmers
placed in pockets or gloves can be most helpful.
Various non-drug treatments are used but it is not
clear that they make a difference. For example, biofeedback
alone does not appear to be helpful. However, stress
reduction and physical conditioning in warm conditions
via exercise are helpful.
Aggravating factors include emotional stress and trauma
to the fingers or toes. Smoking can worsen attacks,
because nicotine decreases blood flow to the fingers
and toes. Certain drugs or medications can potentially
aggravate Raynaud’s attacks. These include over
the counter cold preparations containing sympathomimetics
agents (e.g., Sudafed); caffeinated drinks, clonidine,
ergotamines, serotonin receptor agonists (e.g., migraine
medications), narcotics, and some chemotherapeutic agents.
Use of estrogens or non-selective beta blockers is reported to be associated
with Raynaud’s phenomenon, but this is still controversial.
Drug therapy is not indicated in every case. If the
patient has primary Raynaud’s phenomenon the attacks
are usually mild and do not cause tissue damage. Therefore,
non-drug therapy is recommended unless the attacks are
intense, altering quality of life, and compromising
the ability to perform daily activities. Drug therapy
is recommended in patients with secondary Raynaud’s
phenomenon who have severe attacks or if there is evidence
of tissue damage such as digital ulcerations.
The most common medications are calcium channel blockers
such as nifedipine or amlodipine. Most cases can be
managed with appropriate doses of a calcium channel
blocker. Older agents used with some success include
alpha-adrenergic blockers (e.g., prazosin) or local
applications of nitroglycerin preparations. Newer approaches
include the use of angiotensin receptor inhibitors (e.g.,
losartan), phosphodiesterase inhibitors (e.g., cilostazol,
sildenafil), serotonin uptake inhibitors (e.g., fluoxetine),
and intravenous prostaglandins (e.g., iloprost, epoprostenol).
In complex or severe cases, combinations of these agents
are tried.
Digital ulcers can have a significant impact on patients,
causing pain and functional impairment. Pain can be
effectively managed in various ways. If Raynaud’s
events are severe and associated with critical tissue
damage (e.g., gangrene or digital ulcers) that is not
responsive to medical therapy, then surgical sympathectomy
can be done. Sympathectomy is a surgical procedure that
is performed to improve blood flow in the digital arteries
by destroying nerves in the sympathetic nervous system.
However, surgical sympathectomy often provides only
temporary relief and should be coupled with continued
drug therapy. Digital ulcers are best handled with regular
soap and water washing, antibiotics, and good vasodilator
therapy. In cases of delayed healing, or if signs and
symptoms of infection (e.g., swelling, excessive pain,
or drainage) develop or the digit becomes discolored,
contact your physician for further evaluation.
Acknowledgments
The Scleroderma Foundation thanks Frederick Wigley,
M.D., Professor of Medicine, Division of Rheumatology,
Department of Medicine, at Johns Hopkins University;
and Daniel Wallace, M.D., Clinical Professor of Medicine
at Cedars-Sinai/UCLA School of Medicine in Los Angeles,
for their assistance in the preparation of this text. |
