bubble_chart Overview

Vitiligo is an acquired, localized or generalized skin depigmentation disorder, a common skin disease that affects aesthetics. It is easy to diagnose but difficult to treat. Traditional Chinese medicine refers to it as "Bai Dian" or "Vitiligo."

bubble_chart Etiology

The exact cause of this disease remains unclear. Recent studies suggest it may be related to the following factors:

1. Genetic Theory: Some research indicates that vitiligo may be an autosomal dominant inherited skin disease. Foreign authors have reported a 30% positive family history among patients, with both monozygotic twins affected in some cases. Domestic reports show a positive family history rate of 3–12%, lower than foreign statistics.
2. Autoimmune Theory: The relationship between autoimmune mechanisms and vitiligo pathogenesis has gained increasing attention. Many scholars have noted a higher incidence of autoimmune diseases among patients and their family members, including thyroiditis, hyperthyroidism or hypothyroidism, diabetes, chronic adrenal insufficiency, pernicious anemia, wind-dampness arthritis, and malignant melanoma. In vitiligo patients, various organ-specific antibodies have been detected in serum, such as anti-thyroid antibodies, anti-gastric parietal cell antibodies, anti-adrenal antibodies, anti-parathyroid antibodies, and anti-smooth muscle antibodies, with significantly higher detection rates. Additionally, the incidence of vitiligo is 10–15 times higher in individuals with autoimmune diseases compared to the general population. Recent studies have also identified antibodies against melanocyte surface antigens in vitiligo patients, termed vitiligo antibodies. Their titers correlate with the degree of skin depigmentation and increase with the expansion of lesions. Similar phenomena have been observed in animals with vitiligo, supporting the theory that this disease is an autoimmune disorder targeting melanocytes. Behl (1977) observed mononuclear cell aggregation at the edges of progressing vitiligo lesions, infiltrating the dermo-epidermal junction and entering the epidermis through disrupted basement membranes, leading to melanocyte and melanin loss. This suggests vitiligo may be a delayed-type hypersensitivity autoimmune reaction. Furthermore, the efficacy of systemic or topical corticosteroids, especially for non-dermatomal lesions, indirectly supports the immune mechanism of this disease.
3. Psychoneural Chemical Theory: Many clinicians have observed a close link between psychological factors and vitiligo onset. Approximately two-thirds of patients experience emotional trauma, excessive stress, depression, or distress during disease onset or progression. Stress can elevate catecholamine levels (e.g., adrenaline), which directly affect depigmentation. Stress also increases ACTH secretion, leading to elevated corticosteroid levels, mobilizing glucose and free fatty acids while stimulating insulin secretion. Insulin indirectly boosts brain L-tryptophan, increasing serotonin synthesis. The metabolic byproduct of serotonin, melatonin, plays a critical role in vitiligo pathogenesis when its receptor activity is excessive. Overactive melatonin receptors enhance the activity of certain enzymes that inhibit melanin generation and transformation. However, in later stages, these enzymes reactivate melanin production, causing toxic intermediates to accumulate in melanocytes, leading to their death and ultimately vitiligo. Degenerative changes in nerve endings at depigmented sites, correlating with disease duration, further support the neurochemical theory.
4. Melanocyte Self-Destruction Theory: The fundamental pathology of vitiligo is partial or complete functional loss of epidermal melanocytes. Proposed by Lerner in 1971, this theory suggests that vitiligo results from hyperactive melanocytes undergoing premature exhaustion, possibly due to cytotoxic melanin precursors synthesized by the cells themselves. Experiments confirm that certain chemicals selectively destroy melanocytes, causing skin depigmentation. These substances, primarily substituted phenols like hydroquinone monobenzyl ether, hydroquinone, butylphenol, and hydrogen peroxide, have depigmenting effects on skin and hair. The rising incidence of vitiligo may correlate with industrial development and increased exposure to such chemicals.
5. Trace element deficiency theory: Some propose that decreased copper levels in the body are related to the onset of vitiligo, but measurements of copper content in patients' serum and hair show no significant difference compared to the general population. The trace element theory requires further research.
6. Other factors: Trauma, including wounds, surgery, scratching, etc., can induce vitiligo. Certain endocrine diseases, such as hyperthyroidism and diabetes, may be associated with vitiligo. Excessive sun exposure is also prone to trigger vitiligo.

There are numerous theories regarding the pathogenesis of vitiligo, each with some supporting evidence but also certain limitations. Currently, it is believed that the onset of vitiligo involves genetic factors combined with the influence of various internal and external factors, leading to dysfunctions in immune response, nervous and endocrine systems, and metabolic processes. These disruptions result in the inhibition of enzyme systems, destruction of melanocytes, or impairment of melanin formation, ultimately causing the loss of skin pigmentation.

bubble_chart Pathological Changes

Vitiligo skin shows a significant reduction or absence of epidermal melanocytes and melanin granules. The number of dopa-positive melanocytes in the basal layer is reduced or absent.

bubble_chart Clinical Manifestations

Among ethnic groups worldwide, both men and women can be affected. The incidence varies by region and skin color, generally being higher in populations with darker skin tones. For example, the prevalence is less than 1% in the United States but as high as 4% in India, while in China, it ranges from 0.1% to 2%. There is no significant gender difference, and the condition can occur at any age, though it is more common in adolescents, with about half of cases developing before the age of 20. The skin lesions, characterized by localized depigmented patches, can appear anywhere on the body. These patches are often milky white or light pink, with smooth surfaces and no rash. The borders are well-defined, and the surrounding skin may exhibit increased pigmentation. Hair within the patches may remain normal or turn white. Lesions frequently occur in sun-exposed or friction-prone areas, such as the face, upper legs, neck, extensor surfaces of the forearms, back of the hands, waist, abdomen, sacrococcygeal region, armpits, genitals, and elbow and knee joints. The distribution is often symmetrical. In some cases, the patches follow a dermatomal or neural segmental pattern, appearing in a linear or unilateral arrangement. Besides the skin, mucous membranes such as the lips, labia, glans penis, and inner foreskin may also be affected. While the patches can spread extensively, melanocytes in the retina, choroid, and leptomeninges remain unaffected. Occasionally, repigmentation may occur after sun exposure, while in winter, the center or edges of the patches may show reduced pigmentation. About 20% of patients are highly sensitive to ultraviolet (UV) light, with rapid progression of lesions after sun exposure. Mechanical stimuli (e.g., pricking, scratching, pressure from tight clothing or hernia supports) and other local irritants (e.g., burns, infections, sunburns, frostbite, or radiation) can induce new patches or expand existing ones, sometimes triggering a generalized isomorphic response. The number of patches varies—some remain stable or resolve spontaneously, but most cases involve gradual enlargement and merging into irregular, large patches, potentially spreading across the body.

Most patients experience no subjective symptoms, though a few may report localized cutaneous pruritus before or during the onset. Vitiligo is often associated with other autoimmune disorders, such as diabetes, thyroid diseases, adrenal insufficiency, pernicious anemia, rheumatoid arthritis, scleroderma, atopic dermatitis, and alopecia areata.

Clinically, vitiligo is classified into four types based on lesion morphology, location, extent, and treatment response: 1. **Localized type**: Single or clustered patches in one area. 2. **Generalized type**: Scattered patches of varying sizes, often symmetrically distributed. 3. **Universal type**: Extensive involvement, covering over half of the body surface, usually progressing from the above types. 4. **Segmental type**: Patches following a dermatomal or neural segmental distribution. Additionally, the disease can be divided into **complete** and **incomplete** types based on depigmentation severity. The complete type shows a negative dihydroxyphenylalanine (DOPA) reaction, absence of melanocytes, and poor treatment response. The incomplete type has a positive DOPA reaction, reduced melanocyte count, and a higher likelihood of treatment success.

bubble_chart Treatment Measures

The treatment of this disease is quite difficult. Although there are many drugs and methods available, the efficacy is poor, the treatment course is long, and recurrence is possible after recovery.

1. Psoralen and its derivatives As early as the 13th century, Egyptians used a plant called Ammi majus to treat vitiligo. After 1947, three crystalline substances were extracted from it: ① δ-methoxypsoralen (δ-MOP, ammoidin); ② δ-isoamylenoxypsoralen (ammidin); ③ 5-methoxypsoralen (majudin). Among these, δ-MOP has the best efficacy in pigment production. The above compounds are all photosensitive and require supplementation with sunlight or ultraviolet irradiation. The mechanism of treating vitiligo may involve acting on epidermal melanocytes adjacent to damaged cells that are not yet completely destroyed or normal melanocytes, stimulating their function, catalyzing melanin synthesis via tyrosinase, promoting melanocyte division and migration, and restoring normal skin color.

(1) Oral administration of δ-MOP Suitable for patients with numerous and extensive white patches. Take 10–20 mg daily, divided into two doses after meals. Sunlight or long-wave ultraviolet (UVA) irradiation is performed 2 hours after taking the medication, known as photochemotherapy (PUVA). Generally, sunlight exposure should not exceed 5 minutes. Pigmentation usually appears after 16–24 treatments, with optimal results achieved after more than 10 treatments. If no improvement is observed after 6–12 months of continuous treatment, it may be considered ineffective. Side effects of the drug include loss of appetite, anemia, leukopenia, and toxic hepatitis. Therefore, it is contraindicated in patients with diabetes, SLE, porphyria, or liver dysfunction. Oral administration should be stopped 3 days before prolonged outdoor activities. During treatment, avoid consuming sour oranges, wild celery herb, mustard greens, carrots, etc.

(2) Topical application of δ-MOP Apply 0.2%–0.5% δ-MOP solution to the affected area, followed by phototherapy 1–2 hours later. Alternatively, 0.1% δ-MOP lotion or tincture can be applied to the affected area, followed by sunlight or ultraviolet irradiation after 1–2 hours.

(3) Trimethylpsoralen (δ-trimethylpsoralen, trisoralen, TMP) This is a synthetic compound with lower toxic reactions compared to δ-MOP. The oral dose is 10–50 mg daily, taken once a day, followed by sunlight or long-wave ultraviolet irradiation 2–4 hours after administration. The dose should be reduced for children. No significant side effects are observed, but the efficacy is unreliable, and repigmentation is not long-lasting, requiring prolonged treatment.

When using photosensitizing drugs, the eyes should be protected from ultraviolet injury. For this purpose, wear UV-protective sunglasses for 24 hours after taking the medication and take the drug in the evening.

(4) Psoralea A commonly used Chinese medicinal for treating vitiligo. It contains psoralen. After grinding, soak 30 g of raw herb in 95% alcohol per 100 mL for 5–6 days, then apply the filtered solution to the affected area, followed by sunlight or long-wave ultraviolet irradiation.

2. Corticosteroids Corticosteroids may inhibit melanocyte antibodies, protecting melanocytes from destruction.

(1) Systemic medication Taking prednisone as an example, 5 mg is taken orally three times daily for 1.5–2 months. After significant improvement, reduce the dose by one tablet every 2–4 weeks until reaching one tablet every other day, maintaining this for 3–6 months. If no improvement is observed after 3 months, discontinue treatment. This method is more effective for exposed areas and generalized lesions, especially for rapidly progressing skin lesions under stress or those associated with autoimmune diseases. Sometimes, adding corticosteroids may yield results when psoralen alone is ineffective.

(2) Topical application ① Corticosteroid-containing creams or solutions can be applied to the vitiligo-affected areas. Commonly used medications include triamcinolone acetonide cream, clobetasol propionate cream, and eflucort cream. In recent years, Sicorten cream has shown relatively good efficacy. However, such medications may cause capillary dilation and skin atrophy, so caution is advised when using them on facial vitiligo. ② Intralesional injection: Triamcinolone acetonide suspension (10mg/mL) can be injected into the vitiligo lesions, usually once a week, with each dose not exceeding 10mg. To prevent skin atrophy, the treatment should not exceed 6 injections.

3. Copper and Zinc Preparations Some patients have been found to lack certain trace elements, such as copper and zinc. After supplementing the deficient elements, their condition improves or even recovers. Commonly used is 0.5% copper sulfate solution, 10 mL diluted with water or milk, taken three times daily, with reduced dosage for children. Alternatively, copper sulfate solution can be used for iontophoresis at the affected area once daily. For those with zinc deficiency, 0.25g of licorice root zinc can be taken 2–3 times daily, or 0.14g of zinc gluconate 2–3 times daily.

4. Immunomodulators Drugs used include levamisole, transfer factor, and thymosin. Levamisole is taken at 50 mg three times daily for three consecutive days every two weeks. Transfer factor is administered subcutaneously at 1–2 units per dose, twice weekly. Thymosin is given at 5–10 mg per dose, twice weekly.

Recently, some reports indicate that cyclosporine A has shown good efficacy in treating six cases. There are also reports on the use of inosine pranobex.

5. Depigmentation Therapy When the affected area exceeds 50% and does not respond to drug treatment, or in cases of generalized lesions with only small patches of normal skin in exposed areas where patients are unwilling to undergo repigmentation therapy, depigmentation therapy may be performed for cosmetic purposes. The commonly used agent is monobenzyl ether of hydroquinone (MBEH), which causes irreversible destruction of melanocytes. To minimize irritation, the initial concentration is 10%, applied topically twice daily. If no irritation occurs, the concentration can be increased to 20% within 2–3 months. Complete depigmentation takes 6–24 months. Side effects include dermatitis, cutaneous pruritus, and in severe cases, dry skin, alopecia areata, and premature hair graying. Avoid close skin contact with others for at least 2–3 hours after application.

6. Cover-Up Therapy When vitiligo affects appearance, artificial pigment-based cover-up agents can be applied to the affected area to approximate normal skin color. Commercially available products like Tianzi Cover-Up Cream are an option. We have used 0.2–5% dihydroxyacetone alcohol solution on affected areas with good results.

7. Surgical Therapy For patients unresponsive to drug therapy, surgical treatment may be considered. Contraindications include hypertrophic scars and keloid predisposition. ① Autologous suction blister epidermal grafting: Using negative pressure (26.66–39.99 kPa, 200–300 mmHg), blisters are induced. The blister roof epidermis containing melanocytes is excised and transplanted onto the depigmented area where the epidermis has been removed by liquid nitrogen or PUVA-induced blistering. The success of this method depends on the type and location of vitiligo and the blistering technique. This method leaves no scars but is complex and requires specialized equipment. ② Autologous minigrafting (punch grafting): Small skin grafts are harvested from normal skin on the outer thigh or inner upper arm using a punch tool. Similar-sized punches are made on the depigmented area, and the normal skin grafts are transplanted into the recipient sites. Punch diameters are 1.5–2 mm, with grafts spaced 4–5 mm apart. Topical antibiotics and microporous tape are applied, with dressings removed after 7 days. Repigmentation occurs 3–4 weeks post-surgery. ③ Autologous melanocyte transplantation: Melanocytes are isolated from the patient’s normal epidermis and cultured. After inducing blisters on the depigmented area with negative pressure, blister fluid is aspirated with a 25-gauge needle, and the cultured melanocyte suspension is injected into the blister cavity. Repigmentation may appear after four weeks.

8. Other Surgical Methods ① 5-FU/Dermabrasion: Tsuji et al. treated 28 cases of vitiligo by applying 5-FU cream twice daily for 7–10 days on dermabraded lesions, achieving complete repigmentation in 64% of cases. The mechanism remains unclear. Infection and isomorphic reactions are its side effects. ② Micro-pigmentation (Tattooing): Halder et al. implanted iron oxide pigment into the dermis using micro-pigmentation technology, showing good short-term efficacy but significant pigment loss soon after. Side effects are the same as above. ③ Active Pigment (Vitadye) can be used for staining and covering prominent lesions. Covermark, a cosmetic product, offers various shades and provides excellent coverage.

bubble_chart Differentiation

The diagnosis is easily made based on the characteristics of the lesion, but differentiation from the following diseases is necessary:

1. Pityriasis alba: Small patchy vitiligo on the face should be differentiated from pityriasis alba. The white patches of pityriasis alba have indistinct borders, no increased pigmentation in the surrounding skin, and a surface covered with grayish-white scaly scales.
2. Tinea versicolor: The lesions occur at the posterior hairline, forehead, back, and upper limbs, presenting as faint white round or oval patches with indistinct borders and fine scales on the surface; fungal tests are positive.
3. Anemic nevus: Present at birth due to a local lack of capillaries, the surrounding skin reddens when rubbed, while the white patch remains unchanged.
4. Albinism: A congenital, non-progressive condition often with a family history, characterized by a lack of pigment in the skin and hair throughout the body, transparent irises, and absence of choroidal pigment, making it easily distinguishable.