Raynaud Syndrome - Raynaud Disease

Raynaud syndrome, also known as Raynaud's is a medical condition in which there are episodes of reduced blood flow due to spasm of arteries. Typically the fingers, and less commonly the toes, are involved. Rarely, the nose, ears, or lips are affected. The episodes result in the affected part turning white and then blue. Often there is numbness or pain. As blood flow returns, the area turns red and burns. The episodes typically last minutes but can last up to several hours.

Episodes are often triggered by cold or emotional stress. There are two main types: primary Raynaud's when the cause is unknown and secondary Raynaud's which occurs as a result of another condition. Secondary Raynaud's can occur due a connective tissue disorder such as scleroderma or lupus, injuries to the hands, smoking, 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 stimulants use. Medications for treatment of cases that do not improve include calcium channel blockers and iloprost. Little evidence supports alternative medicine. Severe disease may rarely be complicated by skin sores or gangrene.

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

Signs and symptoms

The condition can cause pain within the affected extremities, discoloration (paleness), and sensations of cold and/or numbness. This can often be distressing to those who are not diagnosed, and sometimes it can be obstructive. If someone with Raynaud's is placed into a cold climate, it could potentially become dangerous.

1. 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.
2. When the oxygen supply is depleted, the skin color turns blue (called cyanosis).
3. 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. Nifedipine, a calcium channel blocker and vasodilator, was recommended to increase blood flow to the extremities and noticeably relieved pain in the breast in an extremely small study group.

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 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.

Smoking increases frequency and intensity of attacks, and there is a hormonal component. Caffeine also worsens the attacks. Sufferers 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
  • systemic lupus erythematosus
  • rheumatoid arthritis
  • Sjögren's syndrome
  • dermatomyositis
  • polymyositis
  • mixed connective tissue disease
  • cold agglutinin disease
  • Ehlers-Danlos syndrome
• Eating disorders:
  • anorexia nervosa
• Obstructive disorders:
  • atherosclerosis
  • Buerger's disease
  • Takayasu's arteritis
  • subclavian aneurysms
  • thoracic outlet syndrome
• Drugs:
  • beta-blockers
  • cytotoxic drugs â€" particularly chemotherapeutics and most especially bleomycin
  • ciclosporin
  • bromocriptine
  • ergotamine
  • sulfasalazine
  • anthrax vaccines whose primary ingredient is the Anthrax Protective Antigen
  • stimulant medications such as those used to treat ADHD
  • OTC psedoephedrine medications (Chlor-Trimeton, Sudafed, others)
• 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
  • malignancy
  • 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)

Raynaud's can herald these diseases by periods of more than twenty years in some cases, making it effectively their 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.

Mechanism

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

Diagnosis

It is important to distinguish Raynaud's disease (primary Raynaud's) from phenomenon (secondary Raynaud's). 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.

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 pressure: 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: this may reveal a normocytic anaemia suggesting the anaemia of chronic disease or renal failure.
• Blood test for urea and electrolytes: this may reveal renal impairment.
• Thyroid function tests: this may 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.

To aid in the diagnosis of Raynaud's 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 Raynaud's phenomenon by a panel of multiple experts in the fields of rheumatology and dermatology.

Management

Secondary Raynaud's is managed primarily by treating the underlying cause and as primary Raynaud's, 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 RP.

• Vasodilators â€" calcium channel blockers such as the dihydropyridines nifedipine, amlodipine or diltiazem, preferably slow release preparations â€" 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. Peoples whose RP is secondary to erythromelalgia often cannot use vasodilators for therapy as they trigger 'flares' causing the extremities to become burning red due to there being too much blood.
• People with severe RP 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.
• 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 there is some evidence 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 RP, and the endothelin receptor antagonist bosentan is used to manage severe pulmonary hypotension and prevent finger ulcers in scleroderma.
• Statins have a protective effect on blood vessels, and SSRIs such as fluoxetine may help RP symptoms but the data is weak.

Surgery

• In severe cases, a Endoscopic thoracic sympathectomy (ETS) 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. This procedure should be considered as a last resort however.
• 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 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, 3 more had gradual pain reduction over 1â€"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.

References

Further reading

• Bakst R, Merola JF, Franks AG, Sanchez M (October 2008). "Raynaud's phenomenon: pathogenesis and management". Journal of the American Academy of Dermatology. 59 (4): 633â€"53. doi:10.1016/j.jaad.2008.06.004. PMID 18656283. 

External links

• What Is Raynaud's Disease at National Heart, Lung, and Blood Institute
• Questions and Answers about Raynaud’s Phenomenon at National Institutes of Health
• Overview at Medical College of Wisconsin