Introduction
In 1862, Maurice Raynaud described episodes of discoloration of the skin of the digits on exposure to cold, and he thought this was due to increased sensitivity of the sympathetic nervous system. This condition, which is limited to the skin, usually accompanied by cyanosis, rubor, pain or paresthesia, and associated gangrene, came to be termed Raynaud’s disease. (1) More than a century later, the pathogenesis, diagnosis, and treatment are still unclear. (2)
An episode typically begins when one or more of the digits appear white as the patient is exposed to cold environment or touches a cold object. This blanching or pallor is considered the ischemic phase, and is caused by vasospasm of the digital arteries. The arterioles and venules dilate following the vasospasm, causing a cyanotic appearance, due to the deoxygenated blood in these vessels. This phase is often accompanied by sensations of cold or numbness or paresthesia. Upon rewarming, the vasospasm resolves and blood flow returns dramatically to the affected area. This phase is sometimes accompanied by a painful, throbbing sensation, and the digits may turn bright red as warmth returns.
The event, or series of events, described is known as Raynaud’s phenomenon, which is broadly classified into two categories. The idiopathic variety, termed Raynaud’s disease, is applied when secondary causes of Raynaud’s phenomenon have been ruled out. The secondary variety is associated with other disease states or other known causes of vasospasm.
Over 50 percent of patients with Raynaud’s phenomenon have Raynaud’s disease. Women are affected about five times more often than men, and the age of presentation is usually between 20 and 40 years. (3) One interesting group of patients with Raynaud’s symptoms comprises those whose occupations involve routine use of vibratory equipment, or frequent exposure to cold temperatures. From 40 to 90 percent of loggers and 50 percent of miners using vibratory equipment have been diagnosed with Raynaud’s disease. Heredity may also play a role in the development of this disease. (4) Frequency also seems to be increased in pianists and typists, and electric shock injury or frostbite may also predispose a later development of Raynaud’s phenomenon. Raynaud’s phenomenon occurs in 80-90 percent of patients with systemic sclerosis (scleroderma) and is the presenting symptom in 30 percent. It may be the only symptom of scleroderma for many years. (5)
Other causes of secondary Raynaud’s phenomenon include atherosclerosis of the extremities, (frequently seen in men over age 50), collagen vascular diseases, arterial occlusive diseases, pulmonary hypertension, neurogenic lesions such as carpal tunnel syndrome or thoracic outlet syndrome, and certain blood dyscrasias.
Several drugs have been implicated to cause Raynaud’s phenomenon. These include beta-blockers, ergot preparations, methysergide, amphetamines, imipramine, bromocriptine, clonidine, cyclosporin, cocaine, and the chemotherapy drugs; bleomycin, vincristine, and cisplatin.
Two theories of the cause of digital artery vasospasm in primary Raynaud’s disease are an increased activity of the sympathetic nervous system, and a local fault in the digital arteries. (6) In general, persons with Raynaud’s disease seem to have a milder form than those with secondary Raynaud’s phenomenon.
Statistic
Raynaud’s and Scleroderma Association, 2005.
- Raynaud’s disease affects between 3-20% of the adult population worldwide.
The National Arthritis and Musculoskeletal and Skin Diseases Information Clearing House(NAMSIC)/ National Institutes of Health, 1997.
- Although estimates vary, recent surveys show that Raynaud’s phenomenon may affect 5 to 10 percent of the general population in the United States.
- Women are more likely than men to have the disorder.
- Raynaud’s phenomenon appears to be more common in people who live in colder climates.
- People with the disorder who live in milder climates may have more attacks during periods of colder weather.
- Approximately 75 percent of all cases are diagnosed in women who are between 15 and 40 years old.
Signs and Symptoms
The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.
Blanching of the skin of the digits occurs as the patient is exposed to cold or touches a cold object. This may be followed by a cyanosis and paresthesia. Upon rewarming, rubor occurs, accompanied by a throbbing or burning pain in the fingers. Primary Raynaud’s disease usually includes the following; vasospastic attack induced by cold exposure, bilateral involvement of the extremities, absence of gangrene or involvement of only the skin of the fingertips. A history of symptoms exists for at least 2 years. These symptoms also usually occur without evidence of underlying disease including absence of antinuclear antibodies, a normal erythrocyte sedimentation rate, and normal nailfold capillaroscopy and esophageal motility studies. (7) The symptoms of an acute attack are digital color changes (blanching, sometimes cyanosis), rubor and paresthesias.
Acute attack
- Digital color changes (blanching, sometimes cyanosis)
- Rubor
- Paresthesias (numbness, tingling, burning, or a feeling of tightness)
Treatment Options
Conventional
For the majority of patients with primary Raynaud’s disease, or secondary Raynaud’s phenomenon, conservative measures are all that may be necessary. The most important of which are avoidance of cold temperatures, tobacco, emotional situations, and certain drugs. These patients should dress warmly and use lined gloves if they must go out in the cold. They should protect the trunk, head, and feet with warm clothing to prevent cold-induced reflex vasoconstriction.
Drug treatment should be reserved for severe cases. The calcium channel antagonists, particularly nifedipine (10-30mg three times daily) and diltiazem (30-90mg three times daily), decrease the frequency and severity of Raynaud’s. (8)
Adrenergic blocking agents, such as reserpine, have been shown to increase blood supply to the fingers. Short-term effects seem to be positive in most patients; however, long-term improvement is doubtful. The dose should be 0.25-0.75mg daily, as higher doses cause several unpleasant side effects (hypotension, nasal stuffiness, lethargy, and depression). The alpha-adrenergic antagonist, prazosin, has been used with favorable responses at doses of 1-5mg, three times daily. Adverse effects such as dizziness, headache, fatigue, and edema may occur as patients become tolerant to drug effects and must have dosage increases.
Treatment with doxazosin and terazosin may also be effective. Treatment with vasodilator prostaglandins is under investigation, and has been reported to improve symptoms in patients with scleroderma. Techniques of biofeedback have also been used with variable degrees of success for teaching patients to control the temperature of the hands.
Nutritional Supplementation
Magnesium
One study reported that women with primary Raynaud’s phenomenon have lower erythrocyte magnesium levels than healthy controls during the winter months, which is the time when the symptoms of this condition are likely to be worse. (9) Some studies have reported that magnesium sulfate intravenous infusions are therapeutically useful in treating individuals with Raynaud’s disease. (10) , (11) Although clinical trials on oral magnesium for Raynaud’s disease have not been conducted, some physicians recommend supplementing with 300 to 500 mg of magnesium daily.
Antioxidant Nutrients
One study reported that patients with Raynaud’s disease had lower levels of vitamin C and selenium compared to healthy controls. (12) Inadequate levels of antioxidant nutrients increases the risk of oxidative tissue damage. Since it is known that antioxidant nutrients are synergistic and complementary in their activities, it might be appropriate to recommend a combination of antioxidant nutrients to patients with Raynaud’s disease. The primary antioxidants to consider along with average suggested dosages are vitamin C (500 to 1,000 mg 2 or 3 times daily), vitamin E (400 daily), vitamin A (10,000 IU daily), beta-carotene (25,000 IU daily), and selenium (200 to 300 mcg daily). Two other important antioxidants worthy of consideration are coenzyme Q10 (30 to 60 mg daily) and lipoic acid (50 to 100 mg daily).
Vitamin B3
Vitamin B3 in the form of inositol nicotinate, provides mild vasodilation effects, which can provide some symptomatic improvement in patients with Raynaud’s disease. (13) , (14) However, it has been suggested that the benefits from inositol nicotinate are not solely the result of vasodilation. Other mechanisms such as enhanced fibrinolysis and a reduction of serum lipids may also contribute to inositol nicotinate’s overall effects. (15) The results of another study reported that continuous long-term therapy for 9 months provided greater improvements in peripheral circulation compared to the transient benefits obtained in short-term studies. (16)
Folic Acid, Vitamin B6
A study has reported that individuals with Raynaud’s disease have homocysteine levels that are substantially higher compared to healthy controls. (17) Elevated homocysteine can lead to vascular occlusion, which causes greater circulatory problems. It is well documented that folic acid, vitamin B6, and vitamin B12 are required to metabolize homocysteine. Therefore, it might be wise to check homocysteine levels in patients with Raynaud’s disease. Patients with elevated homocysteine should be instructed to take supplemental levels of these B-vitamins.
Omega-3 Fatty Acids
Omega-3 fatty acids are known to have beneficial effects on aspects of coagulation and circulation. These beneficial effects could be therapeutically useful to patients with Raynaud’s disease. To study this possibility, a group of patients with Raynaud’s disease were instructed to take either 12 fish oil capsules daily, containing 3.96 grams of EPA and 2.64 grams of DHA, or 12 placebo capsules containing olive-oil. After initial baseline measurements, progress was assessed after 6, 12, and 17 weeks of therapy. Consumption of the omega-3 fatty acids provided substantial increases in the median time interval before the onset of Raynaud’s vasospasms and improved tolerance to cold. (18) These results suggest that supplementation with omega-3 fatty acids from fish oils can be an important part of therapy programs for patients with Raynaud’s disease.
Arginine
Arginine is a precursor for the production of nitric oxide in humans. Because nitric oxide is a vasodilator, it helps to improve blood supply and oxygenation to tissues. (19) This relationship between arginine and nitric oxide explains why arginine is sometimes recommended as a natural product in the treatment of Raynaud’s syndrome. (20) However, some studies have reported that arginine supplementation does not result in improved digital circulation. (21) , (22) The results from these studies suggest that the circulatory problems in patients with Raynaud’s disease are probably related to abnormalities in prostaglandin biochemistry rather than being under the influence of the circulatory effects of the arginine/nitric oxide pathway.
7-Keto Dehydroepiandrosterone (DHEA)
7-keto DHEA may be helpful in reducing primary attacks of Raynauds phenomenon by inhibiting vasospasm, though there exists limited clinical data. (23)
Herbal Supplementation
Hawthorn
Hawthorn is used as a vasodilator and circulatory stimulant. (24) It has been used extensively by doctors in Europe in its standardized form in various cardiovascular and peripheral circulatory conditions. Its combination of effects on the heart leads to its use as a tonic, especially for the elderly where mitral stenosis and minor heart failure may be present. Studies have reported a reduction in blood pressure due to arteriosclerosis and chronic nephritis with the use of hawthorn. (25) It is also used for peripheral vascular diseases, such as Raynaud’s disease. Hawthorn is used in Europe by physicians to help maintain digoxin levels while decreasing the need for the pharmaceutical medication. Hawthorn is reported to have the ability to regulate both low and high blood pressure. Its bioflavonoids reportedly dilate both peripheral and coronary blood vessels. (26) This leads to its use in decreasing angina attacks. The proanthocyanidin (PCO) content is claimed to support the spasmolytic effects. (27) The PCO content also is thought to be responsible for the coronary circulatory effects, increasing the amplitude of the heartbeat. (28) Hawthorn’s glycoside component reportedly increases the vagal tone of the heartbeat. (29) It is also thought that hawthorn inhibits angiotensin-converting enzyme. (30) It has a slight diuretic effect which may help lower high blood pressure. Laboratory studies have reported that proanthocyanidins may actually aid in reversing atherosclerotic plaque. (31)
Ginkgo
Ginkgo is among the oldest living species on earth and has been used extensively as a medicinal agent worldwide for centuries, and is the most frequently prescribed medicinal herb in Europe. The most dramatic benefits are reported in improving circulation in the elderly. (32) , (33) This can lead to enhanced memory, delaying the onset of Alzheimer’s, (34) and reducing senile dementia, (35) tinnitus, (36) and vertigo. (37) Ginkgo’s memory-enhancing effects are reported in younger populations as well. The main active components of ginkgo are the flavoglycosides. These compounds act as strong free radical scavengers or antioxidants. (38) Ginkgo is also reported to inhibit platelet activating factor (PAF) which could reduce the adhesive nature of platelets possibly through competitive binding. Ginkgo may foster vasodilation by stimulating endothelium releasing factor and prostacyclin. (39) It may also stimulate venous tone and improves the clearance of homotoxins during ischemic episodes. (40) Gingko reportedly acts as a tonic for the circulatory system. It may increase cerebral brain flow and, therefore, improve delivery of nutrients to the brain, enhancing elimination of the byproducts of cell metabolism and oxygenating the tissues. (41) Ginkgo may normalize acetylcholine receptors and, therefore, improve cholinergic function. (42)
Grape Seed Extract
Proanthocyanidins (PCOs), the active constituent in grape seed, is a flavonoid-rich compound which are being heavily touted as some of the most potent free radical scavengers to date. They have been reported to enhance the absorption of and work synergistically with vitamin C. (43) PCOs have been reported to inhibit the release of mediators of inflammation, such as histamine and prostaglandins, and for protection of the microvascular system. (44) , (45) Proanthocyanidins are reported to neutralize many free radicals, including hydroxyl, lipid peroxides, and iron-induced lipid peroxidation. (46) , (47) , (48) They may inhibit the enzyme xanthine oxidase. (49) PCOs have been used in allergies because of their reported ability to inhibit degradation of mast cells and the subsequent release of histamine and other mediators of inflammation.
Cayenne
Cayenne pepper (chili pepper), has been used as a spice for foods in many cultures and as a traditional medicine for centuries, especially with the Native American culture. Cayenne is regarded as an aphrodisiac, depurative (removes waste products), digestive aid, carminative, antispasmodic, diaphoretic (increase sweating), rubefacient, and counterirritant. It has been used historically to treat asthma, pneumonia, diarrhea, cramps, toothache, flatulent dyspepsia without inflammation, and peripheral circulation insufficiency. (50) Externally, topical preparations of capsicum oleoresin (0.25-0.75%), is used for pain associated with arthritis, rheumatism, and cold injuries. Taken orally, capsicum has been reported to increase peripheral circulation and improve digestion.
Capsaicin is reported to selectively activate some unmyelinated primary afferent sensory neurons (Type “C”). Many of cayenne’s positive effects on the cardiovascular system are thought to be due to excitation of neurons in the vagus nerve. (51) Some of the unmyelinated sensory fibers sensitive to capsaicin contain the neuropeptides Substance P and somatostatin. Capsaicin reportedly stimulates the release of these neuropeptides from both central and peripheral terminals of these primary afferent neurons. (52) The release of the neuropeptide Substance P is associated with desensitization, analgesia, and anti-inflammatory activity. Prolonged exposure to capsaicin results in a gradual desensitization to acute effects, potentially due to the depletion of substance P and somatostatin from the primary afferent neurons. Topically, capsaicin has been reported to be useful in alleviating post-herpetic neuralgia, post-mastectomy pain syndrome, arthritis and rheumatoid arthritis, painful diabetic neuropathy, psoriasis, pruritus, and other conditions. (53) , (54)
Substance P, a calcitonin peptide, is the main transmitter released from capsaicin-sensitive sensory-motor fibers having positive inotropic and chronotropic effects on the heart. This causes vasodilatation in the coronary arteries and elsewhere in the peripheral vasculature. (55) Capsicum has been reported to have immunomodulatory effects, causing local vasodilation and increased accumulation of neutrophils. (56)
In another study, the effects of dietary hot red pepper on energy metabolism at rest and during exercise were examined in long distance male runners. (57) Plasma epinephrine and norepinephrine levels were significantly higher in those who had only hot red pepper at 30 min. after the meal. These results suggest that hot red pepper ingestion stimulates carbohydrate oxidation at rest and during exercise.
Both the gastric and duodenal mucosa are thought to contain capsaicin-sensitive areas which afford protection against acid and drug induced ulcers when stimulated by capsaicin or hydrochloric acid. Stimulation causes an increase in mucosal blood flow and/or vascular permeability, may inhibit gastric motility, and may activate duodenal motility. (58) Internal use of capsicum in laboratory animals was recently reported to reduce oral bioavailability of aspirin, likely as a result of the gastrointestinal effects of capsaicin. (59)
Acupuncture & Acupressure
Zhang treated 31 cases of Raynaud’s disease with acupuncture. All patients with affected fingers were treated at acupoints Que Pen (ST12) and Shi Xuan (EX-UE 11). Depending on which fingers were primarily affected, patients received the additional treatment as follows: patients primarily with the thumb and index finger affected were treated at Shou Wu Li (LI 13); patients primarily with the middle finger affected were treated at Nei Guan; and patients primarily with the ring and little finger affected were treated at Xiao Hai (SI 8). Patients with affected toes were treated at acupoints San Yin Jiao (SP 6) and Zhao Hai (KI 6), with supplemental treatment at Zu Shi Xuan (EX-UE 11), Huan Tiao (GB 30), or Zhi Bian (BL 54). After insertion, the needles were retained for 20 minutes. The treatment was conducted once daily, and one course of treatment lasted 18 days. The results: after 2-4 courses of treatment, 21 cases were resolved, and the remaining 10 cases had greatly improved, with a total effectiveness rate of 100%. (60)
Jin treated 32 cases of Raynaud’s disease with electro acupuncture. Patients with affected upper extremities were treated at acupoints Qu Chi (LI 11), Shou San Li (LI 10), Wai Guan (TE 5), He Gu (LI 4), Ba Xie (EX-UE 9), and Shi Xuan (EX-UE 11) by blood-letting; and patients with affected lower extremities were treated at acupoints Zu San Li (ST 36), San Yin Jiao (SP 6), Jie Xi (ST 41), Tai Chong (LR 3), Ba Feng (EX-LE 10), and Shi Xuan (EX-UE 11) by blood-letting. After insertion, the needles were retained for 30 minutes. The treatment was conducted once daily, and one course of treatment lasted 10 days. The results: after 1-4 courses of treatment, 13 cases were resolved, 12 cases demonstrated great improvement, another 6 cases slightly improved, and the remaining 1 case did not respond to the treatment. (61)
Wu used warm-needle acupuncture in treating 20 cases of Raynaud’s disease. Patients received treatment at the following acupoints: He Gu (LI 4), Wai Guan (TE 5), Shou San Li (LI 10), San Yin Jiao (SP 6), Zu San Li (ST 36), and Guan Yuan (CV 4). After insertion, the needles were manipulated using the reinforcing method, while 3-5 moxa cones were applied to the needles to deliver heat. The treatment was conducted once daily, and one course of treatment lasted 10 days. The results: 11 cases had greatly improved, and the remaining 9 cases improved slightly. (62)
Treatment with Acupuncture and Acupoint Injection
Han et al. treated 42 cases of Raynaud’s disease with acupuncture combined with acupoint injection. Acupoint injection: 0.2ml of a scopolamine injection was injected at each of the following points: Zhong Zhu (TE 3), He Gu (LI 4), Wai Guan (TE 5), Qu Chi (LI 11), and Jian Yu (LI 15). In addition, acupuncture treatment was applied at Bai Hui (GV 20), Feng Chi (GB 20), Da Zhui (GV 14), Ji Quan (HT 1), Qu Chi (LI 11), Chi Ze (LU 5), Nei Guan (PC 6), and Shen Men (HT 7). The treatment alternated the use of acupuncture and acupoint injection, and one course of treatment lasted 20 days. The results: after 2-4 courses of treatment, 26 cases were resolved, 11 had greatly improved, another 4 cases slightly improved, and the remaining 1 case did not respond to the treatment. (63)
Acupoint He-Ne Laser Therapy
Sun et al. treated 40 cases of Raynaud’s disease with acupoint He-Ne laser therapy. Calibrated for 8mW and 6328 A (angstrom), the He-Ne laser was applied to the Jing acupoints of the affected fingers or toes (for instance, if the little finger was affected, Shao Chong (H 9) was treated; likewise, if the ring finger was affected, Guan Chong (SJ 1) was treated) for 10 minutes each. The treatment was conducted once daily, and one course of treatment lasted for a month. The results: after two courses of treatment, 26 cases were resolved, another 10 cases significantly improved, and the remaining 4 cases slightly improved. (64)
Traditional Chinese Medicine
Raynaud’s Disease
Extensive information regarding the treatment of this health condition using Traditional Chinese Medicine is available through the link above.
Clinical Lab Assessment
Some of the following laboratory testing can provide information necessary for diagnosis and treatment. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.
Thyroid Profile
Raynaud’s phenomenon has been known to accompany thyroid disorders.
Organic Acids
Certain biochemical intermediates reflect sufficiency of nutrient cofactors (vitamins of the B complex, magnesium, some amino acids, and many others) that are important in carbohydrate, neurotransmitter, and fatty acid metabolism, among other vital functions. Organic acids analysis is a useful method for measurement of biochemical intermediates in urine. Stress response can deplete enzymes dependent on these cofactors for synthesis. Chronic stress may also interfere with proper digestion and result in increased allergic response (65) and imbalanced gastrointestinal flora. A subset of organic acids, the dysbiosis markers, may provide useful information regarding gastrointestinal pathogens that can contribute to immune compromise.
Antinuclear antibodies (ANA)
ANA are produced against inherent DNA and nuclear material that cause tissue damage (characteristic of autoimmune disorder). The highest levels occur in SLE. ANA can be use to aid in differentiation of various disease groups, including Raynaud’s syndrome, but it is not diagnostic.
Anti-Smooth Muscle (Sm)
Antibody is an immunoglobulin specific against a ribonucleoprotein found in the cell nucleus. This is a highly specific test for SLE, rarely found in other rheumatic diseases, however, only about 1/3 of patients with SLE are positive for Anti-Sm. This screening test is commonly used in the presence of Raynaud’s symptoms.
Fatty Acids
Dietary polyunsaturated fatty acids (PUFA) are primarily composed of w-3 and w-6 fatty acids. PUFA are vital in the production of eicosanoids – components involved in regulating inflammatory response, blood vessel leakage, lipid accumulation, immune cell response, and optimal control of virtually every body tissue. (66)
Cryoglobulin, Qualitative
These abnormal serum proteins precipitate at low laboratory temperatures and redissolve after being warmed. Presence in the serum causes vascular problems (usually in the extremities) and is associated with immunological disease. Positive cryoglobulin occurs in Raynaud’s disease.
Anti-RNP
Antibody titers are elevated in mixed connective tissue disease and may be used in screening in the presence of Raynaud’s symptoms.
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