Raynaud syndrome is a functional peripheral vascular disorder in which small arteries, also referred to as arterioles, shrink more severely than usual on cold exposure. This phenomenon usually occurs in the hands and the feet.

Raynaud syndrome is divided into two categories:

• Primary Raynaud's when no apparent cause can be detected (also called Raynaud disease);
• Secondary Raynaud's, meaning a preliminary cause can be identified (also called Raynaud phenomenon).

What is Raynaud Syndrome?

Raynaud's syndrome represents the reversible vasospasm of the peripheral arteries. Most frequently, color changes (pallor, followed by cyanosis and/or redness) are associated with symptoms such as pain and paresthesia. Ulceration of the fingers and toes is a rare complication, and similarly, Raynaud syndrome can also affect the ears and the nose.

Types of Raynaud's

Raynaud's syndrome was reported in 1862 by physician Auguste Gabriel Maurice Raynaud in his doctoral thesis. Two major types are outlined: primary and secondary.

Primary Raynaud's (Raynaud's disease) occurs in the absence of any other illness, and its signs and symptoms are usually (but not always) moderate.

Secondary Raynaud's (Raynaud's syndrome) is diagnosed when another illness is present. Although less common, secondary Raynaud's is much more capable of producing severe health problems. Often associated with diseases that attack the body's connective tissues, such as lupus or rheumatoid arthritis, its clinical presentation includes skin sores and gangrene, which happen when cells and tissues die from lack of blood flow.

Anatomy and Physiology of Thermoregulation

Homeostasis controls body temperature, maintaining it around 37°C, which is the temperature at which enzymes within the human body thrive. The hypothalamus, which is located in the brain, contains receptors sensitive to the temperature of the blood, forming the thermoregulatory center. This vast array of receptors also receives information from the skin, which sends upstream signals regarding the environment’s temperature.

The typical response upon exposure to excessive heat is the production of sweat by the sudoriferous glands in the skin. This cools the body through evaporation, transferring heat energy from the skin to the environment. More blood flows to the skin thanks to the process of dilation – the widening of blood vessels or vasodilation.

Conversely, when exposed to cold, skeletal muscles react by contracting rapidly and producing shivers. These quick contractions release heat, warming the body. An effort to conserve the core temperature of the body is achieved by narrowing the skin capillaries – this is called vasoconstriction.

Another contributor to thermoregulation is the hair on the skin, which usually lies flat, but rises in cold temperatures. When experiencing severe cold, nerve impulses are sent to the hair erector muscles, which contract, raising the hairs and efficiently trapping a layer of insulating air next to the skin.

Thermoregulation is an excellent example of a negative feedback mechanism. It modulates the amount of:

• shivering (heat production through quick muscular contractions)
• sweating (cooling through the evaporation of water)
• blood flow to the skin capillaries

Raynaud's syndrome occurs when this complex system has pathological abnormalities.

Risk Factors

The risk factors tend to be different for primary Raynaud's (Raynaud's disease) and secondary Raynaud's (Raynaud's phenomenon), as presented in the following sections.

The risk factors for primary Raynaud's include:

• Gender - women are more likely to have primary Raynaud's than men
• Age - primary Raynaud's usually has an onset before the age of 30
• Family history - primary Raynaud's may occur in members of the same family
• Living in a cold environment - cold temperatures often trigger Raynaud's attacks

The risk factors for secondary Raynaud's include:

• Age - secondary Raynaud's usually develops in patients over 30
• Certain diseases and conditions such as those that directly damage the arteries or the nerves that regulate the arteries in the hands and feet
• Previous trauma to the hands or feet
• Exposure to chemicals within the workplace, for example, vinyl chloride, which is used in the plastics industry
• Tasks carried out using the hands, such as typing or using vibrating tools
• Medications, such as those used for migraines, cancer, cold/allergy, or blood pressure
• Tobacco smoking
• Living in a cold climate (populations of the Northern hemisphere)

Raynaud Syndrome Causes

The cause of primary Raynaud's phenomenon is yet to be found. When it's cold, your body tries its best to preserve heat; therefore, the areas farthest from your heart, such as the extremities (hands and feet), will receive less blood flow. This is done through the vasomotor response, which narrows the network of arterioles that carry blood to those locations.

In Raynaud's, this typically quick response is off – the arterioles shrink faster and more than expected, leading to numbness and changes in color (to white or blue) in the fingers and the toes. One episode may last about 15 minutes; its final phase is characterized by a sensation of tingling and another color change – this time, red – before returning to normal. It has been studied if there are specific genes that control this response, but there hasn't been found a link between this and Raynaud's.

What Causes Secondary Raynaud's?

Secondary Raynaud's is similar from a pathophysiological standpoint, but instead of idiopathic, it is caused by underlying conditions, such as:

• Connective tissue diseases - scleroderma patients often suffer from Raynaud's. Lupus, rheumatoid arthritis, and Sjogren's syndrome also make it more likely;
• Arterial disease - including atherosclerosis (plaque buildup in the coronary arteries); Buerger's disease, which causes inflammation in the blood vessels of the hands and feet; primary pulmonary hypertension (high blood pressure affecting blood vessels in the lungs).
• Carpal tunnel syndrome - pressure on the median nerve can cause numbness, pain, and increased cold sensitivity in the hands;
• Repetitive movements or vibrations – playing the piano or using a jackhammer
• Smoking, which narrows blood vessels;
• Trauma - this includes injuries to your hands or feet from fractures, surgery, or frostbite;
• Some medications such as high blood pressure treatments (beta-blockers, migraine meds with ergotamine or sumatriptan, ADHD medications, certain types of chemotherapy, cold medications).

Is Raynaud Syndrome autoimmune?

While most cases of secondary Raynaud's are linked to autoimmune conditions, such as rheumatoid arthritis and lupus, Raynaud's has not been proven to be an autoimmune disease. 

Associated diseases in patients with Raynaud's syndrome

Some of the autoimmune or connective tissue diseases associated with Raynaud's are:

• Lupus (systemic lupus erythematosus);
• Scleroderma;
• CREST syndrome (a form of scleroderma);
• Buerger disease;
• Sjögren syndrome;
• Rheumatoid arthritis;
• Occlusive vascular disease, such as atherosclerosis;
• Polymyositis;
• Blood disorders, such as Cryoglobulinemia;
• Thyroid disorders;
• Pulmonary hypertension.

Scleroderma and Raynaud's

Scleroderma patients will commonly see Raynaud's syndrome as an early sign of systemic disease. Other signs and symptoms of scleroderma vary depending on which part of the body is affected. The skin is affected almost always, most of the patients experiencing hardened and tightened patches of skin. Scleroderma causes Raynaud's syndrome by excess collagen that narrows small blood vessels in the fingers and toes.

The digestive system can also become affected, with scleroderma patients often experiencing heartburn or dysphagia. If the affected portion of the GI tract is lower, symptoms may include cramps, bloating, diarrhea, or constipation. This autoimmune disease can become life-threatening if it affects the function of the heart, lungs, or kidneys.

The type of Raynaud's disease that is associated with scleroderma can be extremely severe, to the point of permanently damaging the tissue at the fingertips, causing pits or skin sores, and even requiring amputation in some cases.

Raynaud's Syndrome Symptoms

• Raynaud's Syndrome Fingers

Symptoms in fingers usually appear when the skin reaches a lower temperature, such as in cold weather or work environment. By eliminating the stimulus, all these effects may be reversed. The return of normal color and feeling is accelerated by rewarming the hands.

The first phase of an episode is represented by pallor and low temperature of the fingers due to narrowing of the blood vessels. This is followed by cyanotic modifications, or, in severe cases, the fingers will turn black. This represents a clear sign of a lack of oxygen in the tissues.

The fingers then go bright red due to dilation of the blood vessels and the return of blood flow. This is associated with sensations of tingling, throbbing, numbness, and pain that can be severe.

These classic color changes are not mandatory – some patients develop bouts of pale, cold fingers, which can feel uncomfortable. In most cases, the fingers are the only body part that's affected, but in others, the toes suffer as well. Seldom, other extremities are affected, including the nose, earlobes, nipples, or tongue. These episodes may last anywhere from minutes to hours.

Patients who do see color changes usually follow a pattern of clear demarcation across the digit: triphasic (pallor, cyanosis, and post warming erythema due to reactive hyperemia), biphasic (cyanosis, erythema), or uniphasic (pallor or cyanosis only). These changes are usually symmetric by comparison to the other hand. Raynaud syndrome most commonly affects the middle three fingers (rarely, the thumb), and it does not appear proximal to the metacarpophalangeal joints. In primary Raynaud's, the episodes are rarely severe enough to cause tissue damage.

• Raynaud's Syndrome Feet

For people who suffer from Raynaud Syndrome, the feet may be one of the most affected areas.

Physical and emotional stress often triggers attacks. Examples of physical stress include diving into cold water or walking for longer distances, especially in a cooler environment. The feet become cold, numb, and even painful because of vasospasm. Their color changes gradually, from white to blue. As the attack subsides, patients may experience paresthesia in their lower limbs as the blood vessels return to normal.

Even though attacks of Raynaud's typically do not cause permanent injury, they may be a factor that contributes to the formation of foot ulcers in some patients, most specifically for those who have diabetes. It is of utmost importance that in Raynaud's syndrome, toes are well taken care of. Broken skin can cause sores and become infected because of diminished healing capabilities due to impaired circulation. Without treatment, patients could suffer gangrene, loss of a toe, or amputation of the foot.

Diagnosis

A clear diagnosis of Raynaud's phenomenon can be made by a series of findings, such as clearly demarcated pallor of digit/s or toe/s, followed by at least one-color change, either cyanosis or erythema, which is usually preceded by exposure to cold.

Findings suggesting primary Raynaud syndrome are as follows:

• Age at onset < 40 (in 2/3 of cases);
• Moderate symmetric attacks affecting both hands;
• Absent tissue necrosis or gangrene;
• Idiopathic.

Findings suggesting secondary Raynaud syndrome are as follows:

• Age at onset > 30;
• Severe painful attacks that may be asymmetric and unilateral;
• Ischemic injury;
• History could be suggesting an underlying disorder.

Laboratory testing

Clinical findings may be followed-up by vascular laboratory testing, which measures digital pulse waveforms and pressures.

Diagnostic blood tests can also be used for collagen vascular diseases (e.g., measurement of erythrocyte sedimentation rate or C-reactive protein, antinuclear and anti-DNA antibodies, rheumatoid factor, anti-centromere antibody, anti-cyclic citrullinated peptide antibodies, and anti-scleroderma 70 antibodies).

Complications

In general, complications occur only in secondary Raynaud's syndrome patients. These may or may not include:

• hindered healing of cuts and abrasions;
• increased vulnerability to infection;
• ulceration;
• tissue wasting;
• scarring;
• gangrene.

Raynaud Syndrome Treatment

The first line of therapy in primary Raynaud's syndrome is characterized by lifestyle changes. Although lifestyle alterations are very efficient, drug therapy is more commonly used than behavioral treatments because of convenience.

Therapy for secondary Raynaud phenomenon must be customized to the underlying disorder. Patients with secondary Raynaud phenomenon are more likely to require pharmacologic therapy. If the disease proves to be unresponsive to all other measures (as well as treating the underlying illness) and the disability is progressively unresponsive, patients may choose to undergo cervical or local sympathectomy. This surgical act often abolishes the symptoms, but with temporary results – relief may last 1 to 2 years.

The initial treatment for Raynaud's Syndrome in most patients includes education and lifestyle alterations to maintain body warmth and avoid other triggers, such as stress. If proven unsuccessful, pharmacological treatment may begin with dihydropyridine CCBs being the favored first-line agents. Alternative options for patients who have contraindications to or do not tolerate CCBs include monotherapy with either a phosphodiesterase (PDE) type 5 inhibitor, a topical nitrate, an angiotensin receptor blocker, or a serotonin reuptake inhibitor.

General Measures

Patients should be informed about situations that can cause an attack, such as putting their hand in a fridge or freezer, holding an ice-cold drink, and going into an air-conditioned area, such as the frozen goods section of the supermarket, or swimming in cold water. This is an approach to avoiding a known trigger based on our understanding of the pathophysiology behind this disease. There are no randomized clinical trials so far to investigate this approach.

Strategies to maintain whole body and digital warmth

Generally, patients with Raynaud's phenomenon are advised to use strategies that maintain the warmth not only of the hands and feet (e.g., gloves, thick socks) but of the entire body. Some of these strategies include wearing warm thermal underwear, layering clothes, and wearing head coverings. It is also important to ensure appropriate heating at home and the workplace. A strong trigger may also be sitting still in cold breezes from AC units or being involved in situations where ambient temperature changes rapidly from warm to cold.

It is important to understand that one must keep the whole body warm and not just the hands and feet. Therefore, it is advised that patients with Raynaud's phenomenon use strategies that not only keep the digits warm (e.g., hand warmers, warm socks) but also the whole body. 

Strategies to maintain body warmth include dressing warmly with thermal underwear, layered clothing, and a hat when going outside and arranging to have appropriate heating in both the home and working environment. This also includes measures to avoid whole-body cold exposure, such as not sitting still in cold breezes from air conditioning and avoiding situations that involve rapid changes from a warm to cold ambient temperature. Winter gloves, chemical hand warmers, and heavy wool socks can help keep the digits and toes of the hands and feet warm.

Gloves for Raynaud's Syndrome

Several types of gloves, including battery-heated gloves and gloves tied with silver thread, have been advocated for people with Raynaud's phenomenon to lessen the frequency of attacks. The only randomized trial to assess customized gloves, specifically ceramic-impregnated gloves, exhibited severe methodological flaws, making the results difficult to interpret.

Patients should also be taught how to stop a Raynaud's attack from getting worse. These include submerging the hands in warm water or placing them in a warm location (such as the axilla), as well as moving the arms in a whirling or windmill pattern. A Frisbee-like movement can also be utilized. Rubbing hands together might also assist in warming them and improving blood flow. After rewarming, a typical attack lasts about 15 to 20 minutes.

Lifestyle

Nicotine commonly contributes to secondary Raynaud syndrome but is often overlooked. Smoking cessation is one of the first lifestyle changes Raynaud's patients must make. Smoking has a number of adverse effects, including vasoconstriction and changes in wound healing. A comprehensive study involving over 600 individuals with systemic sclerosis discovered that smoking was linked to significantly worsening Raynaud's phenomenon symptoms and that symptom severity decreased after quitting.

Increased sympathetic tone constricts the thermoregulatory vessels; therefore, patients should control or limit their exposure to emotional stress. This, when combined with cold exposure, represents an incredibly potent trigger for a Raynaud's attack. Because of a lack of studies regarding the subject, it has been challenging to define the exact impact of stress and anxiety on the severity of symptoms.

There are a few examples of studies worth mentioning: in a laboratory study of patients with primary Raynaud's phenomenon, finger temperature dropped when subjects witnessed a cold-related stress situation; an ambulatory study in over 300 patients with primary Raynaud's phenomenon found a link between anxiety and the severity of the symptoms.

To this date, behavioral therapy such as biofeedback or relaxation therapy has not been supported by clinical trial evidence as a treatment for Raynaud's syndrome.

Avoidance of vasoconstricting drugs

When possible, patients should be encouraged to avoid drugs that aggravate vasospasm. There are essentially no official studies that have investigated the effects of various pharmaceuticals on Raynaud's phenomenon; nonetheless, because some drugs' therapeutic mechanisms are known to produce vasospasm, these treatments should be avoided. Several medication classes have been linked to vasospasm, including the following:

• Over-the-counter upper respiratory tract decongestants (e.g., phenylephrine, pseudoephedrine);
• Amphetamines, diet pills, and herbs with ephedra;
• Drugs used for attention deficit hyperactivity disorder (ADHD) (methylphenidate and dextroamphetamine);
• Some medications are used for migraine headaches, including serotonin agonists (e.g., sumatriptan) or ergotamine.

Prognosis

Patients with primary Raynaud phenomenon typically have a very favorable prognosis, with no mortality and minor morbidity. Ischemia of the damaged body part, on the other hand, might cause necrosis in very unusual circumstances.

Patients with secondary Raynaud phenomenon have a prognosis that is determined by the underlying condition. In these individuals, the prognosis for the implicated digit or digits is determined by the degree of the ischemia and the efficacy of blood flow restoration techniques. 

Patients with secondary Raynaud's are more likely to experience severe attacks and have an illness that lasts or worsens. Patients with systemic rheumatic disease, particularly systemic sclerosis (systemic sclerosis, scleroderma), may develop persistent digital ischemia, requiring intensive but not always effective treatments. Primary Raynaud's phenomenon may remit on its own. In patients with secondary Raynaud's phenomenon, however, remission is uncommon.

Conclusion

Raynaud syndrome is defined as reversible vasospasm of parts of the hand and feet in response to cold or emotional stress. Unlike secondary Raynaud syndrome, primary Raynaud syndrome rarely results in gangrene or tissue loss. Primary Raynaud's phenomenon is a mild illness that is generally temporary, improving or disappearing in one-third or more of patients during the course of seven to fourteen years of follow-up.

Raynaud therapy, both pharmacological and lifestyle changes, aims to increase the quality of life while preventing ischemic tissue harm.

If you are suffering from Raynaud syndrome, make sure you avoid smoking, exposure to the cold, and other triggers.