Raynaud's syndrome: Pathophysiology, Symptoms and Treatment

Raynaud's syndrome is a kind of vasospasm of parts of the hand in response to cold or emotional stress that causes a reversible discomfort and color changes in either one or more digits.

Raynaud’s syndrome was first described in 1862 by Maurice Raynaud.

This syndrome is probably due to an exaggerated alpha 2-adrenergic response that triggers vasospasm.

Reynaud’s phenomenon can be divided into two; that is, Primary and secondary Raynaud’s phenomenon.

Primary Raynaud's syndrome is much more common than a secondary phenomenon occurring in more than 80% of the cases. It is known to occur without features of other disorders.

The underlying cause is unclear and no investigation is necessary.

Secondary Raynaud’s phenomenon occurs in about 20% of patients with Raynaud's symptoms. The causative underlying disease will be evident at the initial presentation or diagnosed subsequently.

Pathophysiology of Raynaud’s syndrome

The primary hallmark of Raynaud’s syndrome is a transient episode of reduced blood flow to the hands and feet, as well as to the nose and outer ear structures.

Initial vasospasm occurs, leading to reduced blood flow to the tissue, associated with a white coloration of the hands or feet. The tissue consumes the oxygen in the limited amount of blood trapped in the area, leading to a blue color.

Subsequently, a red phase occurs during which there is hyperemia, as the episode resolves and blood flow is restored. Quite often, pain is associated with the attack due to sensory nerve ischemia.

Primary Raynaud’s syndrome occurs in the absence of any underlying cause and generally represents a benign condition, although occasionally small ulcerations might arise on the tips of the fingers and toes.

Interestingly, people with primary Raynaud’s syndrome can also experience other vascular disorders, such as coronary vasospasm and migraines. No apparent vascular abnormalities have been identified in these people, although microvascular changes have been reported.

By contrast, secondary Raynaud’s syndrome is a potentially dangerous and life-threatening condition associated with autoimmune disorders, inflammatory conditions, hematopoietic disease or connective tissue conditions, such as scleroderma.

Digital gangrene is often associated with this condition and individuals show both structural changes to the peripheral vasculature and significant alterations to vascular reactivity.

In general, women are more likely than men to experience Raynaud’s syndrome, with symptoms beginning after menarche and often ceasing after menopause.

Interestingly, baseline cutaneous peripheral blood flow in young women is approximately half of that in age-matched young men when adjusted for body mass. Furthermore, sympathetic control of vascular tone is alleviated by warming the hands and subsequent blood flow in young women increases over that of similarly treated young men.

Since cutaneous flow rates are stable across the menstrual cycle, although hormones are likely to be involved in the process, those hormones that fluctuate throughout the cycle are unlikely to be solely responsible for the gender difference.

However, alpha-1-adrenergic receptor-mediated vasoconstriction has been shown to be highest in the luteal phase of the menstrual cycle in normal women, while the alpha-2-mediated response was higher in the follicular phase and lowest in the luteal phase.

It is important to note that blood vessels in the fingers and toes have both post-synaptic alpha-1- and alpha-2-adrenergic receptors, whereas distal vessels, such as the radial arteries, have only alpha-1-receptors, which would imply a key role of the alpha-2-receptors in the vasospasms.

Supporting this contention was the demonstration that alpha-2-antagonists blocked the cold-induced vasoconstriction and that cooling blocked the effects of alpha-1-agonists, leading to vasodilation.

Furthermore, platelets isolated from people with Raynaud’s syndrome have more alpha-2-adrenergic receptors than those of normal controls, and alpha-2-antagonists reduce peripheral vasospasms in susceptible people but do not eliminate them.

Adding to this speculation was the demonstration that individuals who had their digital sympathetic nerves anesthetized or who experience a sympathectomy still experienced vasospastic attacks, implying that a nerve-independent factor was responsible.

Other factors that have been implicated include estrogen, serotonin, endothelin, neurohumoral compounds, such as atrial natriuretic peptide or adrenomedullin, and nitric oxide.

In addition, it is common for family members across generations to manifest the condition, indicating a genetic contribution to disease development.

Symptoms and Signs of Raynaud's syndrome

Sensations of coldness, burning pain, paresthesia, or intermittent color changes of one or more digits are precipitated by exposure to cold, emotional stress, or vibration.

All these features can be reversed by removing the stimulus.

Restoration of normal color and sensation can be accelerated by re-warming the hands.

Color changes are clearly demarcated across the digit. They may be triphasic (pallor, followed by cyanosis and after warming by erythema due to reactive hyperemia), biphasic (cyanosis, erythema), or uniphasic (pallor or cyanosis only).

Changes are often symmetric.

Raynaud's syndrome does not occur proximal to the metacarpophalangeal joints; it most commonly affects the middle 3 fingers and rarely affects the thumb. Vasospasm may last minutes to hours but is rarely severe enough to cause tissue loss.

Raynaud's syndrome secondary to a connective tissue disorder may progress to painful digital gangrene; while the one that is secondary to systemic sclerosis tends to cause extremely painful, infected ulcers on the fingertips

The clinical findings suggesting primary Raynaud's syndrome that may be realized are the following:

• Less than 40 years of age
• Reports of mild symmetric attacks affecting both hands
• No reports of tissue necrosis or gangrene
• No any other suggestive history

Findings suggesting secondary Raynaud's syndrome are the following:

• More than 30 years old
• Severe painful attacks that may be asymmetric and unilateral
• Presence of ischemic lesions
• History and findings suggesting an accompanying disorder v

Diagnosis

Raynaud's syndrome is diagnosed clinically. Clinical examination also enables the clinician to differentiate between Acrocyanosis and Reynaud’s phenomenon. Acrocyanosis also causes a color change of the digits in response to cold but differs from Raynaud's in that it is persistent, not easily reversed, and does not cause trophic changes, ulcers, or pain.

Primary and secondary forms of Reynaud’s phenomenon can be distinguished clinically, supported by vascular laboratory studies and blood testing.

Vascular laboratory testing includes digital pulse waveforms and pressures.

The primary blood testing is the panel for collagen vascular diseases

Laboratory tests

The usual blood works are done to detect any accompanying disorder. These tests include;

Erythrocyte sedimentation rate,

Antinuclear antibodies,

Rheumatoid factor,

ant centromere antibody,

Anti-SCL-70 antibody.

Treatment of Raynaud's syndrome

The patient with Raynaud's syndrome should be reassured and advised to avoid exposure to cold and stop smoking or any stress.

Usually, no other treatment is required.

Calcium channel blockers can be used if the symptoms are troublesome to the patient. Examples of calcium channel blockers used are; Nifedipine, Amlodipine, Felodipine, isradipine followed by an alpha-adrenergic blocker, prazosin, which may provide temporary relief to secondary Raynaud's phenomenon.

A more severe Raynaud’s syndrome can also occur in association with digital ulceration in patients with connective tissue disease. In this case, drugs are used more often than behavioral treatments due to convenience.

Topical nitroglycerine paste, pentoxifylline can be taken with meals.

Some drugs such as beta-Blockers, clonidine, and ergot preparations are contraindicated because they cause vasoconstriction and may trigger or worsen symptoms.

Treatment of the secondary form of the syndrome focuses on the underlying disorder.

If a patient has ischemic ulcers, antibiotics, analgesics, and, surgical debridement may be necessary.

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

IV prostaglandins such as alprostadil, epoprostenol or iloprost are effective and may be an option for patients with ischemic digits.

An endoscopic thoracic sympathectomy often temporarily abolish