Raynaud syndrome

Raynaud syndrome, also known as Raynaud's phenomenon, is a medical condition in which spasm of arteries
Raynaud syndrome
cause episodes of reduced blood flow.[1] Typically, the fingers, and less commonly the toes, are involved.[1] Rarely, the
Other names Raynaud's, Raynaud's
nose, ears, or lips are affected.[1] The episodes result in the affected part turning white and then blue.[2] Often,
disease, Raynaud's
numbness or pain occurs.[2] As blood flow returns, the area turns red and burns.[2] The episodes typically last
phenomenon, Raynaud's
minutes, but can last several hours.[2]
syndrome[1]
Episodes are often triggered by cold or emotional stress.[2] The two main types are primary Raynaud's, when the cause
is unknown, and secondary Raynaud's, which occurs as a result of another condition.[3] Secondary Raynaud's can
occur due to a connective-tissue disorder, such as scleroderma or lupus, injuries to the hands, prolonged vibration,
smoking, thyroid problems, and certain medications, such as birth control pills.[6] Diagnosis is typically based on the
symptoms.[3]

The primary treatment is avoiding the cold.[3] Other measures include the discontinuation of nicotine or stimulants
use.[3] Medications for treatment of cases that do not improve include calcium channel blockers and iloprost.[3] Little
evidence supports alternative medicine.[3] Severe disease may rarely be complicated by skin sores or gangrene.[2]

About 4% of people have the condition.[3] Onset of the primary form is typically between ages 15 and 30 and occurs
more frequently in females.[3][4] The secondary form usually affects older people.[4] Both forms are more common in
cold climates.[4] It is named after the French physician Maurice Raynaud, who described the condition in 1862.[3]

Contents
Signs and symptoms A hand with pale fingers due to Raynaud's
Cause Pronunciation /reɪˈnoʊ/ ray-NOH
Primary
Specialty Rheumatology
Secondary
Mechanism
Symptoms An affected part turning white,
then blue, then red, burning[2]
Diagnosis
 Management Complications skin sores, gangrene[2]
Medications
Usual onset 15–30 year old, typically
Surgery
Alternative medicine females[3][4]

Prognosis Duration Up to several hours per

References episode[2]
External links Risk factors Cold, emotional stress[2]
Diagnostic Based on the symptoms[3]
method
Signs and symptoms Differential Causalgia, erythromelalgia[5]
The condition can cause pain within the affected extremities, discoloration (paleness), and sensations of cold and/or diagnosis
numbness. This can often be distressing to those who are undiagnosed, and sometimes it can be obstructive. If Treatment Avoiding cold, calcium
someone with Raynaud's is placed into a cold climate, it could potentially become dangerous. channel blockers, iloprost[3]

When exposed to cold temperatures, the blood supply to the fingers or toes, and in some cases the nose or earlobes, is Frequency 4% of people[3]
markedly reduced; the skin turns pale or white (called pallor) and becomes cold and numb. These events are episodic,
and when the episode subsides or the area is warmed, the blood flow returns, and the skin color first turns red (rubor), and then
back to normal, often accompanied by swelling, tingling, and a painful "pins and needles" sensation.

All three color changes are observed in classic Raynaud's. However, not all patients see all of the aforementioned color changes in
all episodes, especially in milder cases of the condition. Symptoms are thought to be due to reactive hyperemias of the areas
deprived of blood flow.

In pregnancy, this sign normally disappears owing to increased surface blood flow. Raynaud's has also occurred in breastfeeding
mothers, causing nipples to turn white and become extremely painful.[7]

Cause

Primary
Raynaud's disease, or primary Raynaud's, is diagnosed if the symptoms are idiopathic, that is, if they occur by themselves and not
Raynaud's affecting all five fingers
in association with other diseases. Some refer to primary Raynaud's disease as "being allergic to coldness". It often develops in
young women in their teens and early adulthood. Primary Raynaud's is thought to be at least partly hereditary, although specific
genes have not yet been identified.[8]
Smoking increases frequency and intensity of attacks, and a hormonal component exists. Caffeine, estrogen, and nonselective beta-
blockers are often listed as aggravating factors, but evidence that they should be avoided is not solid.[9] People with the condition
are more likely to have migraines and angina.

Secondary
Raynaud's phenomenon, or secondary Raynaud's, occurs secondary to a wide variety of other conditions.

Secondary Raynaud's has a number of associations:

Connective tissue disorders:

scleroderma[10]
Systemic lupus erythematosus
Bluish coloration
Rheumatoid arthritis
Sjögren's syndrome
Dermatomyositis
Polymyositis
Mixed connective tissue disease
Cold agglutinin disease
Ehlers-Danlos syndrome
Eating disorders:

Anorexia nervosa
Obstructive disorders:

Atherosclerosis
Nipple blanching, or vasospasm of
Buerger's disease
the nipple, can cause difficulty
Takayasu's arteritis breastfeeding.
Subclavian aneurysms
Thoracic outlet syndrome
Drugs:

Beta-blockers
Cytotoxic drugs – particularly chemotherapeutics and most especially bleomycin
Cyclosporin
Bromocriptine
Ergotamine
Sulfasalazine
 Anthrax vaccines whose primary ingredient is the Anthrax Protective Antigen
Stimulant medications, such as those used to treat ADHD (amphetamine and methylphenidate)[11]
OTC pseudoephedrine medications (Chlor-Trimeton, Sudafed, others)[12]
Occupation:

Jobs involving vibration, particularly drilling and prolonged use of a string trimmer (weed whacker), suffer from vibration white finger
Exposure to vinyl chloride, mercury
Exposure to the cold (e.g., by working as a frozen food packer)
Others:

Physical trauma, such as that sustained in auto accidents or other traumatic events
Lyme disease
Hypothyroidism
Cryoglobulinemia
Cancer
Chronic fatigue syndrome
Reflex sympathetic dystrophy
Carpal tunnel syndrome
Magnesium deficiency
Multiple sclerosis
Erythromelalgia (clinically presenting as the opposite of Raynaud's, with hot and warm extremities) often co-exists in patients with Raynaud's[13])

Raynaud's can herald these diseases by periods of more than 20 years in some cases, making it effectively the first presenting symptom. This may be the case in the CREST
syndrome, of which Raynaud's is a part.

Patients with secondary Raynaud's can also have symptoms related to their underlying diseases. Raynaud's phenomenon is the initial symptom that presents for 70% of
patients with scleroderma, a skin and joint disease.

When Raynaud's phenomenon is limited to one hand or one foot, it is referred to as unilateral Raynaud's. This is an uncommon form, and it is always secondary to local or
regional vascular disease. It commonly progresses within several years to affect other limbs as the vascular disease progresses.[14]

Mechanism
Its pathophysiology includes hyperactivation of the sympathetic nervous system causing extreme vasoconstriction of the peripheral blood vessels, leading to tissue hypoxia.

Diagnosis
Distinguishing Raynaud's disease (primary Raynaud's) from phenomenon (secondary Raynaud's) is important. Looking for signs of
arthritis or vasculitis, as well as a number of laboratory tests, may separate them. If suspected to be secondary to systemic sclerosis,
one tool which may help aid in the prediction of systemic sclerosis is thermography.[15]

A careful medical history will often reveal whether the condition is primary or secondary. Once this has been established, an
examination is largely to identify or exclude possible secondary causes.

Digital artery pressures are measured in the arteries of the fingers before and after the hands have been cooled. A decrease of
at least 15 mmHg is diagnostic (positive).
Underlying mechanism
Doppler ultrasound to assess blood flow
Full blood count may reveal a normocytic anaemia suggesting the anaemia of chronic disease or kidney failure.
Blood test for urea and electrolytes may reveal kidney impairment.
Thyroid function tests may reveal hypothyroidism.
An autoantibody screen, tests for rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein may reveal specific
causative illnesses or a generalised inflammatory process.
Nail fold vasculature can be examined under the microscope.
To aid in the diagnosis of Raynaud's phenomenon, multiple sets of diagnostic criteria have been proposed.[16][17][18][19] Table 1
below provides a summary of these various diagnostic criteria.[20]

Recently, International Consensus Criteria were developed for the diagnosis of primary Raynaud's phenomenon by a panel of
experts in the fields of rheumatology and dermatology.[20]

Management
Heat signatures of a Raynaud's
Secondary Raynaud's is managed primarily by treating the underlying cause, and as primary Raynaud's, avoiding triggers, such as
hand (top) and a healthy hand
cold, emotional and environmental stress, vibrations and repetitive motions, and avoiding smoking (including passive smoking)
(bottom): Red indicates warm areas
and sympathomimetic drugs.[21] whilst green indicates cool areas.
(Image taken with a thermographic
camera)
Medications
Medications can be helpful for moderate or severe disease.

Vasodilators – calcium channel blockers, such as the dihydropyridines nifedipine or amlodipine, preferably slow-release preparations – are often first-line treatment.[21]
They have the common side effects of headache, flushing, and ankle edema, but these are not typically of sufficient severity to require cessation of treatment.[22] The
limited evidence available shows that calcium-channel blockers are only slightly effective in reducing how often the attacks happen.[23] Although, other studies also reveal
that CCBs may be effective at decreasing severity of attacks, pain and disability associated with Raynaud's phenomenon.[24] People whose disease is secondary to
erythromelalgia often cannot use vasodilators for therapy, as they trigger 'flares' causing the extremities to become burning red due to too much blood supply.
 People with severe disease prone to ulceration or large artery thrombotic events may be prescribed aspirin.[21]
Sympatholytic agents, such as the alpha-adrenergic blocker prazosin, may provide temporary relief to secondary Raynaud's
phenomenon.[21][25]
Losartan can, and topical nitrates may, reduce the severity and frequency of attacks, and the phosphodiesterase inhibitors
sildenafil and tadalafil may reduce their severity.[21]
Angiotensin receptor blockers or ACE inhibitors may aid blood flow to the fingers,[21] and some evidence shows that
angiotensin receptor blockers (often losartan) reduce frequency and severity of attacks,[26] and possibly better than
nifedipine.[27][28]
The prostaglandin iloprost is used to manage critical ischemia and pulmonary hypertension in Raynaud's phenomenon, and
the endothelin receptor antagonist bosentan is used to manage severe pulmonary hypertension and prevent finger ulcers in
scleroderma.[21]
Statins have a protective effect on blood vessels, and SSRIs such as fluoxetine may help symptoms, but the data is weak.[21]
PDE5 inhibitors are used off-label to treat severe ischemia and ulcers in fingers and toes for people with secondary Raynaud's
phenomenon; as of 2016, their role more generally in Raynaud's was not clear.[29]

Surgery
Consensus diagnostic criteria
In severe cases, an endoscopic thoracic sympathectomy procedure can be performed.[30] Here, the nerves that signal the
blood vessels of the fingertips to constrict are surgically cut. Microvascular surgery of the affected areas is another possible
therapy, but this procedure should be considered as a last resort.
Infusions of prostaglandins, e.g. prostacyclin, may be tried, with amputation in exceptionally severe cases.
A more recent treatment for severe Raynaud's is the use of botulinum toxin. The 2009 article[31] studied 19 patients ranging in age from 15 to 72 years with severe
Raynaud's phenomenon of which 16 patients (84%) reported pain reduction at rest; 13 patients reported immediate pain relief, three more had gradual pain reduction over
1–2 months. All 13 patients with chronic finger ulcers healed within 60 days. Only 21% of the patients required repeated injections. A 2007 article[32] describes similar
improvement in a series of 11 patients. All patients had significant relief of pain.

Alternative medicine
Evidence does not support the use of alternative medicine, including acupuncture and laser therapy.[3]

Prognosis
The prognosis of primary Raynaud syndrome is often very favorable, with no mortality and little morbidity. However, a minority develops gangrene. The prognosis of
secondary Raynaud is dependent on the underlying disease, and how effective blood flow-restoring maneuvers are.[33]
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External links
What Is Raynaud's Disease (http://www.nhlbi.nih.gov/health/dci/Diseases/raynaud/ray_what.html) at National Heart, Lung, and
Classification ICD-10: I73.0 (htt D
Blood Institute
Questions and Answers about Raynaud’s Phenomenon (http://niams.nih.gov/Health_Info/Raynauds_Phenomenon/default.asp) at p://apps.who.int/cla
National Institutes of Health ssifications/icd10/br
Bakst R, Merola JF, Franks AG, Sanchez M (October 2008). "Raynaud's phenomenon: pathogenesis and management". Journal owse/2016/en#/I73.
of the American Academy of Dermatology. 59 (4): 633–53. doi:10.1016/j.jaad.2008.06.004 (https://doi.org/10.1016%2Fj.jaad.200
8.06.004). PMID 18656283 (https://www.ncbi.nlm.nih.gov/pubmed/18656283).
0) · ICD-9-CM:
443.0 (http://www.ic
d9data.com/getICD
9Code.ashx?icd9=4
43.0) · OMIM:
179600 (https://omi
m.org/entry/17960
0) · MeSH:
D011928 (https://w
ww.nlm.nih.gov/cgi/
mesh/2015/MB_cg
i?field=uid&term=D
011928) ·
DiseasesDB:
25933 (http://www.d
 iseasesdatabase.co
m/ddb25933.htm)
External MedlinePlus:
resources 000412 (https://ww
w.nlm.nih.gov/medli
neplus/ency/article/
000412.htm) ·
eMedicine:
med/1993 (https://e
medicine.medscap
e.com/med/1993-ov
erview) · Patient
UK: Raynaud
syndrome (https://p
atient.info/doctor/ra
ynauds-phenomeno
n-pro)

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