Raynaud's phenomenon

Raynaud's phenomenon (rāy-NŌZ), in medicine, is a vasospastic disorder causing discoloration of the fingers, toes, and occasionally other extremities. This condition can also cause nails to become brittle with longitudinal ridges. Named for French physician Maurice Raynaud (1834 - 1881), the cause of the phenomenon is believed to be the result of vasospasms that decrease blood supply to the respective regions. Emotional stress and cold are classic triggers of the phenomenon, and the discoloration follows a characteristic pattern in time: white, blue and red.

It comprises both Raynaud's disease (primary Raynaud's), where the phenomenon is idiopathic, and Raynaud's syndrome (secondary Raynaud's), where it is caused by some other instigating factor. Measurement of hand-temperature gradients is one tool used to distinguish between the primary and secondary forms.

It is possible for the primary form to progress to the secondary form.

Prevalence
The phenomenon is more common in women than men, with the Framingham Study finding that 5% of men and 8% of women suffer from it.

Epidemiology
There is a familial component to primary Raynaud's, and presentation is typically before two. Smoking worsens frequency and intensity of attacks, and there is a hormonal component. Caffeine also worsens the attacks. Sufferers are more likely to have migraine and angina than controls.

Secondary Raynaud's has a number of associations:
 * Connective tissue disorders:
 * scleroderma
 * systemic lupus erythematosus
 * rheumatoid arthritis
 * Sjögren's syndrome
 * dermatomyositis
 * polymyositis
 * mixed connective tissue disease
 * cold agglutinin disease
 * Eating disorders
 * Anorexia Nervosa
 * Obstructive disorders
 * atherosclerosis
 * Buerger's disease
 * subclavian aneurysms
 * thoracic outlet syndrome
 * Drugs
 * Beta-blockers
 * cytotoxic drugs - particularly chemotherapeutics and most especially bleomycin
 * cyclosporin
 * ergotamine
 * sulfasalazine
 * Occupation
 * jobs involving vibration, particularly drilling
 * exposure to vinyl chloride, mercury
 * exposure to the cold (e.g. by working packing frozen food)
 * Others
 * hypothyroidism
 * cryoglobulinemia
 * malignancy
 * reflex sympathetic dystrophy
 * Magnesium Deficiency

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

Symptoms
The condition causes painful, pale, cold extremities. This can often be distressing to those who are not diagnosed, and sometimes it can be obstructive. If someone with Raynaud's is placed in too cold a climate, it could potentially become dangerous.

Unilateral Raynaud's, or that which is present only in the hands or feet, is almost certainly primary, and will probably not progress to a secondary condition. In pregnancy, this sign normally disappears due to increased surface blood flow. Raynaud's has also occurred in breastfeeding mothers, causing nipples to turn white and be extremely painful. Nifedipine, a calcium channel blocker and vasodilator was recommended to increase blood flow to the extremities and noticeably relieved pain to the breast, in a extremely small study group.

Investigations
A careful history will often reveal whether the condition is primary or secondary. Once this has been established, investigations are largely to identify or exclude possible secondary causes.
 * Digital artery pressure: pressures are measured in the digital arteries before and after cooling the hands. A drop of 15mmHg or more is diagnostic.
 * Doppler ultrasound: to assess flow
 * Full blood count: this can reveal a normocytic anaemia suggesting the anaemia of chronic disease or renal failure
 * Urea & Electrolytes: this can reveal renal impairment
 * Thyroid function tests: this can reveal hypothyroidism
 * An autoantibody screen, tests for rheumatoid factor, Erythrocyte sedimentation rate and C-reactive protein, which may reveal specific causative illnesses or a generalised inflammatory process
 * Nail fold vasculature: this can be examined under the microscope

Pathophysiology
Primary Raynaud phenomenon, stemming from Raynaud disease, is an exaggeration of vasomotor responses to cold or emotional stress. More specifically, it is a hyperactivation of the sympathetic system causing extreme vasoconstriction of the peripheral blood vessels, leading to tissue hypoxia. Chronic, recurrent cases of Raynaud phenomenon can result in atrophy of the skin, subcutaneous tissues, and muscle. It can also rarely cause ulceration and ischemic gangrene.

Treatment
Treatment options are dependent on the type of Raynaud's present. Raynaud's syndrome is treated primarily by addressing the underlying cause, but includes all options for Raynaud's disease as well. Treatment of primary Raynaud's focuses on avoiding triggers:

General measures

 * Avoidance of any environmental triggers, e.g. cold, vibration, etc. (although emotional stress is a recognized trigger, it tends to be impossible to consciously avoid).
 * Warm clothing for the extremities such as mittens or HeatBands
 * Hormone regulation and assessment of the type of hormonal contraception used, if any. Contraception which is low in estrogen is preferable, and the progesterone only pill is often prescribed.
 * Smoking cessation.

Emergency measures

 * If white finger (Raynaud's) occurs unexpectedly and a source of warm water is available allow tepid to slightly warm water to run over the affected digits while gently massaging the area. Continue this process until the white area turns pink or a normal healthy color.
 * If triggered by exposure in a cold environment, and no warm water is available, place the affected digits in a warm body cavity - arm pit, crotch, or even in the mouth. Keep the affected area warm at least until the whiteness returns to pink or a healthy color, avoid continued exposure to the cold.

Drug therapy

 * Drug treatment is normally with a calcium channel blocker, frequently nifedipine to prevent arterioconstriction. It has the usual common side effects of headache, flushing, and ankle edema; but normally result in not needing to stop the drug.
 * There is some evidence that Angiotensin II receptor antagonists (often Losartan) reduce frequency and severity of attacks, and possibly better than nifedipine.
 * Alpha-1 adrenergic blockers such as prazosin can be used to control Raynaud's vasospasms under supervision of a health care provider.
 * In a study published in the November 8, 2005 issue of Circulation, sildenafil (Viagra) improved both microcirculation and symptoms in patients with secondary Raynaud's phenomenon resistant to vasodilatory therapy. The authors, led by Dr Roland Fries (Gotthard-Schettler-Klinik, Bad Schönborn, Germany), report: "In the present study, capillary blood flow was severely impaired and sometimes hardly detectable in patients with Raynaud's phenomenon. Sildenafil led to a more than 400% increase of flow velocity."

Surgical intervention

 * In intractable cases, sympathectomy and infusions of prostaglandins, e.g. prostacyclin, may be tried, with amputation in exceptionally severe cases.

Alternative and research approaches

 * The extract of the Ginkgo biloba leaves (Egb 761, 80 mg) may reduce frequency of attacks.
 * Two separate gels combined on the fingertip (somewhat like two-part epoxy, they cannot be combined before use because they will react) increased blood flow in the fingertips by about three times. One gel contained 5% sodium nitrite and the other contained 5% ascorbic acid.  The milliliter of combined gel covered an area of ~3 cm². The gel was wiped off after a few seconds.