Raynaud syndrome
Raynaud syndrome, also known as Raynauds phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries causes episodes of reduced blood flow to end arterioles. Typically, the fingers, and less commonly, the toes, are involved. Rarely, the nose, ears, or lips are affected. The episodes classically result in the affected part turning white and then blue. Often, numbness or pain occurs. As blood flow returns, the area turns red and burns. The episodes typically last minutes but can last several hours.Episodes are typically triggered by cold or emotional stress. Primary Raynauds, also known as idiopathic, means that it is spontaneous, of unknown cause, and unrelated to another disease. Secondary Raynauds occurs as a result of another condition and has an older age at onset; episodes are intensely painful and can be asymmetric and associated with skin lesions. Secondary Raynauds 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. Diagnosis is typically based on the symptoms.The primary treatment is avoiding the cold. Other measures include the discontinuation of nicotine or stimulant use. Medications for treatment of cases that do not improve include calcium channel blockers and iloprost. Little evidence supports alternative medicine. Severe disease may in rare cases lead to complications, specifically skin sores or gangrene.About 4% of people have the condition. Onset of the primary form is typically between ages 15 and 30 and occurs more frequently in females. The secondary form usually affects older people. Both forms are more common in cold climates.

Signs and symptoms
The condition can cause localized pain, discoloration (paleness), and sensations of cold and/or numbness.
When exposed to cold temperatures, the blood supply to the fingers or toes, and in some cases the nose or earlobes, is 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 Raynauds. However, not all patients see all of the aforementioned color changes in all episodes, especially in milder cases of the condition. The red flush is due to reactive hyperemia of the areas deprived of blood flow.In pregnancy, this sign normally disappears due to increased surface blood flow. Raynauds has occurred in breastfeeding mothers, causing nipples to turn white and painful.

Causes
Primary
Raynauds disease, or primary Raynauds, is diagnosed if the symptoms are idiopathic, that is, if they occur by themselves and not in association with other diseases. Some refer to primary Raynauds disease as "being allergic to coldness". It often develops in young women in their teens and early adulthood. Primary Raynauds is thought to be at least partly hereditary, although specific genes have not yet been identified.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.

Secondary
Raynauds phenomenon, or secondary Raynauds, occurs secondary to a wide variety of other conditions.
Secondary Raynauds has a number of associations:
Connective tissue disorders:
Scleroderma
Systemic lupus erythematosus
Rheumatoid arthritis
Sjögrens syndrome
Dermatomyositis
Polymyositis
Mixed connective tissue disease
Cold agglutinin disease
Ehlers-Danlos syndrome
Eating disorders:
Anorexia nervosa
Obstructive disorders:
Atherosclerosis
Buergers disease
Takayasus arteritis
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)
OTC pseudoephedrine medications (Chlor-Trimeton, Sudafed, others)
Occupation:
Jobs involving vibration, particularly drilling and prolonged use of a string trimmer (weed whacker), experience vibration white finger
Exposure to vinyl chloride, mercury
Exposure to the cold (e.g., by working as a frozen food packer)
Others:
Physical trauma to the extremities
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 Raynauds, with hot and warm extremities, often co-exists in patients with Raynauds)
Chilblains (also clinically presenting as the opposite of Raynauds, with hot and itchy extremities, however it affects smaller areas than erythromelalgia, for instance the tip of a toe rather than the whole foot)Raynauds can precede these other diseases by many years, making it the first presenting symptom. This may be the case in the CREST syndrome, of which Raynauds is a part.Patients with secondary Raynauds can also have symptoms related to their underlying diseases. Raynauds phenomenon is the initial symptom that presents for 70% of patients with scleroderma, a skin and joint disease.When Raynauds phenomenon is limited to one hand or one foot, it is referred to as unilateral Raynauds. 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.

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

Diagnosis
Distinguishing Raynauds disease (primary Raynauds) from Raynauds phenomenon (secondary Raynauds) is important. Looking for signs of arthritis or vasculitis, as well as a number of laboratory tests, may separate them. Nail fold capillary examination or "capillaroscopy" is one of the most sensitive methods to diagnose RS with connective tissue disorders, i.e. distinguish a secondary from a primary form objectively.If suspected to be secondary to systemic sclerosis, one tool which may help aid in the prediction of systemic sclerosis is thermography.A careful medical history will seek 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).
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.
Tests for rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, and autoantibody screening may reveal specific causative illnesses or an inflammatory process. Anti-centromere antibodies are common in limited systemic sclerosis (CREST syndrome).
Nail fold vasculature (capillaroscopy) can be examined under a microscope.To aid in the diagnosis of Raynauds phenomenon, multiple sets of diagnostic criteria have been proposed. Table 1 below provides a summary of these various diagnostic criteria.Recently, International Consensus Criteria were developed for the diagnosis of primary Raynauds phenomenon by a panel of  experts in the fields of rheumatology and dermatology.

Management
Secondary Raynauds is managed primarily by treating the underlying cause, and as primary Raynauds, avoiding triggers, such as cold, emotional and environmental stress, vibrations and repetitive motions, and avoiding smoking (including passive smoking) and sympathomimetic drugs.

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. 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. The limited evidence available shows that calcium-channel blockers are only slightly effective in reducing how often the attacks happen. Although, other studies also reveal that CCBs may be effective at decreasing severity of attacks, pain and disability associated with Raynauds phenomenon. 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.
Sympatholytic agents, such as the alpha-adrenergic blocker prazosin, may provide temporary relief to secondary Raynauds phenomenon.
Losartan can, and topical nitrates may, reduce the severity and frequency of attacks, and the phosphodiesterase inhibitors sildenafil and tadalafil may reduce their severity.
Angiotensin receptor blockers or ACE inhibitors may aid blood flow to the fingers, and some evidence shows that angiotensin receptor blockers (often losartan) reduce frequency and severity of attacks, and possibly better than nifedipine.
The prostaglandin iloprost is used to manage critical ischemia and pulmonary hypertension in Raynauds phenomenon, and the endothelin receptor antagonist bosentan is used to manage severe pulmonary hypertension and prevent finger ulcers in scleroderma.
Statins have a protective effect on blood vessels, and SSRIs such as fluoxetine may help symptoms, but the data is weak.
PDE5 inhibitors are used off-label to treat severe ischemia and ulcers in fingers and toes for people with secondary Raynauds phenomenon; as of 2016, their role more generally in Raynauds was not clear.

Surgery
In severe cases, an endoscopic thoracic sympathectomy  procedure can be performed. 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.
A more recent treatment for severe Raynauds is the use of botulinum toxin. The 2009 article studied 19 patients ranging in age from 15 to 72 years with severe Raynauds 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 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.

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.

References
External links

What Is Raynauds Disease at National Heart, Lung, and Blood Institute
Questions and Answers about Raynauds Phenomenon at National Institutes of Health
Bakst R, Merola JF, Franks AG, Sanchez M (October 2008). "Raynauds phenomenon: pathogenesis and management". Journal of the American Academy of Dermatology. 59 (4): 633–53. doi:10.1016/j.jaad.2008.06.004. PMID 18656283.