bubble_chart Overview

Raynaud's syndrome refers to paroxysmal spasms of the distal arterial pulses. It often occurs under the influence of factors such as cold stimulation or emotional agitation, manifesting as intermittent changes in the skin color of the extremities, including pallor, cyanosis, and flushing. It is generally more severe in the upper limbs and occasionally seen in the lower limbs.

bubble_chart Etiology

The disease cause of Raynaud's syndrome is still not fully understood. Cold stimulation, emotional hormones, or mental stress are the main triggering factors. Other contributing factors include infections, fatigue, etc. Since the condition often worsens during menstruation and improves during pregnancy, some believe that this syndrome may be related to gonadal function.

Recent advances in immunology have shown that in the vast majority of Raynaud's syndrome patients, there are many abnormalities in serum immunity, with antibodies exceeding the composition of homologous nuclei. Antigen-antibody immune complexes may exist in the patient's serum, which can act through chemical transmitters or directly on sympathetic nerve terminals, leading to vasospastic changes. Clinically, after using drugs that block sympathetic nerve terminals, Raynaud's symptoms can be completely relieved.

Pallor, cyanosis, and flushing are the three stages of skin color changes in Raynaud's syndrome. Pallor is caused by spasms in the small stirred pulse and venules at the fingertips or toes, leading to slow capillary perfusion and thus reduced or absent blood flow in the skin vessels. After a few minutes, due to hypoxia and the accumulation of metabolic products (abdominal mass), the capillaries—and possibly the venules—slightly dilate, allowing a small amount of blood to flow into the capillaries. Rapid deoxygenation then causes cyanosis. Cyanosis appears when the stirred pulse spasm has subsided but venous spasm persists. When the vascular spasm in the extremities is relieved, a large amount of blood enters the dilated capillaries, resulting in reactive hyperemia, and the skin turns flushed. Once normal blood flow through the small stirred pulse is restored and capillary perfusion returns to normal, the episode stops, and the skin color returns to normal.

bubble_chart Clinical Manifestations

Raynaud's syndrome is not uncommon in clinical practice. It is more prevalent in women, with a male-to-female incidence ratio of approximately 1:10. The onset typically occurs between the ages of 20 and 30, rarely exceeding 40 years. Most cases are observed in cold regions and are more frequent during cold seasons. Patients often experience sudden whitening of the fingers after exposure to cold or emotional stress, followed by cyanosis. The episode usually starts at the fingertips and then spreads to the entire finger or even the palm, accompanied by localized coldness, numbness, tingling, and reduced sensation. After several minutes, the skin gradually turns red, warms up, and feels swollen and burning before finally returning to its normal color. Drinking hot beverages, alcohol, or warming the limbs often alleviates the episode. Generally, after removing the cold stimulus, the skin color transitions from pallor to cyanosis, then to redness, and back to normal in about 15–30 minutes. A few patients may present with cyanosis initially without the pallor phase, or transition directly from pallor to redness without cyanosis. During episodes, the radial pulse remains unaffected. Between episodes, aside from slightly cold fingers and mild pallor, no other symptoms are present.

The condition usually affects the fingers but may also involve the toes and, occasionally, the ears and nose. Symmetrical symptom presentation is another key feature of Raynaud's syndrome. For example, the little and ring fingers on both hands are often the first to be affected, followed by the index and middle fingers. The thumbs, due to their richer blood supply, are rarely involved. The degree and extent of skin color changes are identical on both sides. A few patients may initially experience unilateral symptoms before progressing to bilateral involvement.

The disease generally progresses slowly, though in some cases, it advances rapidly with frequent, severe episodes accompanied by finger or toe swelling, each lasting over an hour. Slight drops in temperature or mild emotional stress can trigger these episodes. In severe cases, symptoms persist even in warm seasons, leading to trophic changes in the fingertips, such as nail deformities, brittle nails, pulp atrophy, thinning skin, loss of wrinkles, and occasional fingertip ulcers or even gangrene. However, the radial pulse remains unaffected throughout.

bubble_chart Auxiliary Examination

(I) Laboratory tests: Routine examinations should include antinuclear antibodies indicating systemic connective tissue diseases, rheumatoid factor, immunoglobulin electrophoresis, complement levels, anti-native DNA antibodies, cryoglobulins, and the Coombs test.

(II) Special examinations

1. **Cold stimulation test**: After the fingers are cooled by exposure to cold, photoplethysmography (PPG) is used to record the time required for finger circulation to return to normal. This serves as a simple, reliable, and non-invasive method to assess digital circulation. During the test, the patient should sit quietly indoors (room temperature 26±2°C) for 30 minutes. After recording the baseline digital circulation waveform with PPG, both hands are immersed in ice water for 1 minute, then immediately dried. The finger circulation is then recorded every minute for 5 minutes. In normal individuals, digital circulation returns to baseline within 0–2 minutes, whereas in patients with Raynaud's syndrome, the recovery time is significantly prolonged (exceeding 5 minutes). In normal individuals, the stirred pulse wave is biphasic, featuring a main peak wave and a dicrotic wave. In Raynaud's syndrome patients, the stirred pulse wave is monophasic, with a low, blunt, or even absent peak (Figures 1–2). This test can also be used to evaluate treatment efficacy; if symptoms improve after medication, the recovery time of digital circulation will shorten.
2. **Finger temperature recovery time measurement**: After the fingers are cooled, a thermistor probe is used to measure the time required for the temperature to return to normal, providing an objective basis for diagnosing Raynaud's phenomenon by estimating finger blood flow. In 95% of normal individuals, finger temperature recovers to baseline within 15 minutes, whereas in most Raynaud's syndrome patients, recovery time exceeds 20 minutes. This test can also assess treatment efficacy.
3. **Digital stirred pulse angiography**: If necessary, upper limb stirred pulse angiography can be performed to evaluate digital stirred pulse conditions, aiding in the diagnosis of Raynaud's syndrome. It can also reveal whether there is organic sexually transmitted disease-related vascular pathology. However, stirred pulse angiography is an invasive and relatively complex procedure, making it unsuitable as a routine examination.

Among special examinations, measuring upper limb nerve conduction velocity can help identify potential carpal tunnel syndrome. Hand X-rays may assist in detecting rheumatoid arthritis and digital calcification.

bubble_chart Diagnosis

The vast majority of patients with Raynaud's syndrome can be diagnosed based on a history of intermittent color changes in the skin of the extremities. However, it is best to observe the condition during symptom episodes, including the nature, extent, severity, and duration of the skin color changes. Immersing the patient's hands or feet in cold water or exposing them to cold air can induce these typical symptoms.

To detect potential underlying related diseases as early as possible, the medical history should focus on whether there is a history of systemic connective tissue diseases and vascular disorders such as arteriosclerosis and vasculitis, a history of vascular trauma, a history of medication use such as ergotamine, β-blockers, and contraceptives, and a history of long-term occupational exposure to vibrating tools.

Physical examination should emphasize the observation of signs suggestive of systemic connective tissue diseases, such as thinning or tightening of the skin, telangiectasia, rashes, dry lips; synovial membrane thickening, effusion, or other evidence of arthritis. Carefully examine the skin of the fingers for ulcers or hyperkeratotic areas from healed ulcers; note peripheral arterial pulses; and remain vigilant for the presence of carpal tunnel syndrome. Patients without identified related diseases should undergo long-term follow-up.

bubble_chart Treatment Measures

The most important aspect of treating Raynaud's syndrome should be addressing the underlying disease. The symptomatic treatment of this condition is divided into drug therapy, biofeedback, and surgery, which are selected based on the patient's specific circumstances.

1. Drug Therapy The following drugs are clinically used:

⑴ Priscol: Also known as tolazoline, taken orally at 25–50mg per dose, 4–6 times daily, after meals. For severe local pain and ulcer formation, the dose can be increased to 50–100mg per dose. Intramuscular, intravenous, or intra-arterial injection doses are 25–50mg per dose, 2–4 times daily. Some patients may experience side effects such as tidal fever, syncope, dizziness, headache, nausea, vomiting, and goosebumps.

⑵ Reserpine: Due to its catecholamine-depleting and serotonin-depleting effects, it is a long-standing and effective drug for treating Raynaud's phenomenon, recommended by many authors. Oral doses vary widely. Kontos reported that an oral dose of 1mg/d for 1–3 years can reduce the frequency and severity of symptom attacks.

In 1967, Abboud et al. first reported the use of intra-arterial injection of reserpine for treating Raynaud's syndrome, achieving satisfactory results. In recent years, many scholars have reported that direct puncture of the brachial artery followed by slow injection of reserpine (0.25–0.5mg in 2–5ml of saline) can significantly improve symptoms, with effects lasting 10–14 days. Repeat injections are needed every 2–3 weeks. Due to the risk of arterial injury, this method's use is limited. However, many scholars believe it is still worth trying for severe cases with acral ulcers.

Intravenous regional injection of reserpine is a local administration method. The procedure involves placing a tourniquet above the elbow joint, puncturing a distal vein, inflating the tourniquet to maintain a pressure of 33.3kPa (250mmHg), and then slowly injecting 0.5mg of reserpine dissolved in 50ml of saline into the vein, allowing the medication to reflux to the extremities. This method is simpler than intra-arterial injection and has similar therapeutic effects, generally lasting 7–14 days.

⑶ Nifedipine: A calcium channel blocker that dilates blood vessels by reducing calcium storage or binding capacity in muscle cell membranes, thereby inhibiting action potential formation and smooth muscle contraction. Oral administration of 20mg, three times daily for 2 weeks to 3 months, has been shown in clinical studies to significantly improve symptoms in moderate to grade III Raynaud's syndrome.

⑷ Guanethidine: Has effects similar to reserpine. Oral dose is 5–10mg per dose, three times daily. It can also be combined with phenoxybenzamine at a daily dose of 10–30mg, with about 80% of patients responding effectively.

⑸ Methyldopa: A daily dose of 1–2g can prevent Raynaud's syndrome attacks in most patients. Blood pressure should be monitored during use.

Recently, some experts have reported that the following drugs have also achieved good therapeutic effects in the treatment of Raynaud's phenomenon. (1) Prostaglandins: Both prostaglandin E1 (PGE1) and prostacyclin (PGI2) have the effects of vasodilation and inhibition of platelet aggregation. They show satisfactory efficacy for Raynaud's syndrome with finger infection and gangrene. Intravenous infusion of PGE1 at 10ng/min for 72 hours. Infusion of PGI1 (7.5ng/kg/min for 5 hours) once a week for 3 weeks. The therapeutic effect generally lasts for 6 weeks. (2) Stanozolol: It is an anabolic steroid hormone that activates plasminogen and is reported to dissolve fibrin deposited in the finger's pulse and reduce plasma viscosity. Oral administration of 5mg twice daily for 3 months.

In addition, topical application of 205 nitroglycerin ointment, 4 to 6 times daily, has been clinically shown to significantly reduce the frequency of Raynaud's phenomenon episodes, with marked alleviation of numbness and pain.

Traditional Chinese medicine and acupuncture have certain therapeutic value for this disease, but further clinical research is needed to develop these approaches.

2. Biofeedback Therapy Biofeedback therapy involves detecting and amplifying biological information that is normally imperceptible or difficult to perceive, using specialized equipment. This information is then converted into signals through a recording and display system, allowing patients to become aware of these functional changes. As a result, patients can associate certain sensations with bodily functions and, to some extent, regulate these functions. In 1973, Jacobson reported the use of biofeedback therapy to treat 20 cases of Raynaud's phenomenon. The method involved dividing the 20 cases into two groups of 10 each. The first group used a temperature device connected to a light indicator system to measure skin temperature every 15 seconds. When the temperature rose or stabilized, the light would turn on; it would remain off if the temperature dropped. This provided patients with a visual stimulus reflecting their skin temperature. The second group underwent self-control training, where they were instructed via audio recordings to take deep breaths, relax, and then recall pleasant, warm experiences—such as basking in warm sunlight or lying on a soft beach with gentle waves lapping nearby. Each session lasted one hour. In the first month, sessions were conducted three times weekly; in the second month, twice weekly; and in the third month, once weekly. Patients were also instructed to practice the same exercises at home for 15 minutes daily. The therapeutic effects were similar in both groups. After treatment, when patients entered a cold room at 3.3°C, their skin temperature remained at 21.4°C (compared to 22.2–23.0°C in healthy individuals), whereas before treatment, it would drop to an average of 19.5°C. Biofeedback therapy is a relatively new approach developed over the past decade. It is simple, painless, and free of side effects for patients. Literature reports suggest it has certain efficacy and warrants further exploration.

In recent years, some researchers have achieved relatively satisfactory results using plasma exchange therapy and induced vasodilation therapy, though further studies are needed.

3. Surgical Therapy The vast majority (80–90%) of patients with Raynaud's syndrome experience symptom relief or halted progression after medical treatment. Only a small number of patients—those who show no improvement despite adequate drug dosage and duration, whose condition worsens, whose symptoms severely impact work and life, or who exhibit trophic changes in the fingertips—may be considered for sympathectomy. However, preoperative assessment of vasomotor responses is essential. If the vasomotor index is insufficient, sympathectomy may not yield the desired results. Reports indicate that only 40–60% of patients experience postoperative symptom improvement, and the relief is often short-lived, with symptoms recurring within two years. The procedure is more effective for patients with occlusive vascular disease but less so for those with connective tissue disorders.

Factors affecting postoperative efficacy:

(1) Cold: A significant trigger for this condition, cold can impact postoperative outcomes.

(2) Severity of local vascular lesions: Patients without organic vascular changes in the fingertips tend to respond better, whereas those with such changes show poorer results.

(3) Incomplete sympathectomy or nerve regeneration: Incomplete removal of sympathetic ganglia due to anatomical variations or surgical technique can affect efficacy. Many scholars believe that nerve regeneration after sympathectomy may also influence outcomes.

bubble_chart Prevention

Including avoiding cold stimulation and emotional agitation; abstaining from smoking; avoiding the use of ergotamine, β-receptor blockers, and contraceptive pills; for those with obvious occupational causes (such as prolonged use of vibrating tools or exposure to cold environments), changing jobs if possible. Carefully protect fingers from injuries, as minor trauma can easily lead to fingertip ulcers or other trophic disorders. Drinking small amounts of alcoholic beverages in daily life may improve symptoms. If conditions permit, relocating to a mild and dry climate can further reduce symptom episodes. Alleviating patients' psychological concerns and maintaining optimism are important preventive measures.

bubble_chart Differentiation

Attention should be paid to differentiating it from other vascular dysfunction diseases characterized by changes in skin color.

1. Acrocyanosis: This is a vasospastic disorder caused by autonomic dysfunction. It is more common in young women, with symmetrical and uniform cyanosis of the skin on the hands and feet. Cold can exacerbate the symptoms. It is often accompanied by autonomic dysfunction phenomena such as dermatographism or profuse sweating of the hands and feet. The pathological changes involve persistent spasms of small stirred pulses in the extremities, as well as capillary and venous varicosities, requiring differentiation from Raynaud's syndrome. Patients with acrocyanosis do not exhibit typical skin color changes; the cyanosis is more extensive, affecting the entire hands and feet, and may even extend to the whole limb. The cyanosis lasts for a prolonged period. Although cold can worsen the symptoms, they often do not immediately improve or disappear in a warm environment. Emotional stimuli and mental stress generally do not trigger this condition.
2. Livedo reticularis: Mostly seen in women, it is caused by spasms of small stirred pulses and atonic dilation of capillaries and veins. The skin presents with persistent网状or spotted cyanosis. The lesions mostly occur in the lower limbs and occasionally affect the upper limbs, trunk, and face. The affected limbs often experience coldness, numbness, and paresthesia. The livedo becomes more pronounced in cold conditions or when the limbs are dependent. In a warm environment or after elevating the affected limb, the斑纹减轻或消失. Clinically, it can be divided into three types: cutis marmorata, idiopathic网状purplish macula, and symptomatic livedo reticularis.
3. Erythromelalgia: The disease cause remains unclear. The pathological changes involve symmetrical, paroxysmal vasodilation of the extremities. It is more common in young women. The onset is sudden, with both feet affected simultaneously, and occasionally the hands may be involved. It presents with symmetrical, paroxysmal severe burning pain. When the foot temperature exceeds the critical threshold (approximately 33–34°C), such as when the feet are in warm bedding, the pain can发作, mostly presenting as a burning sensation, but may also be stabbing pain or distending pain. Pain发作can be triggered by dependent positioning of the limbs, standing, or movement, and can be alleviated by elevating the affected limb, resting, or exposing the feet outside the bedding. During发作, the feet exhibit erythema and congestion, elevated skin temperature accompanied by sweating, and enhanced stirred pulse搏动in the dorsalis pedis and posterior tibial arteries. Based on these features, it is easily distinguished from Raynaud's syndrome. A少数cases of erythromelalgia may be secondary to polycythemia vera or diabetes.