Vitiligo

Vitiligo is a common skin disease that occurs in the skin and mucous membranes and is characterized by local or generalized depigmentation, which mainly affects beauty.

I. Etiology and pathogenesis

The etiology and pathogenesis of vitiligo are not yet fully understood. It is currently believed that individuals with genetic predisposition may be stimulated by multiple internal and external factors, inducing abnormalities in immune function, mental neuroendocrine function, metabolic function, etc., which leads to the loss of tyrosinase function in melanocytes at the junction of the epidermis and dermis, causing tyrosine oxidation to DOPA-blocked melanin formation disorders, and ultimately causing skin depigmentation.
1. Genetic theory believes that patients often have a family history, and it is generally believed to be an autosomal dominant inheritance with different penetrances. Foreign statistics show that the incidence of vitiligo in patients' families is 18.75%~40%, and domestic statistics show that it is 3%~12%. Vitiligo may be a multi-gene genetic disease, which may be due to congenital deficiency of tyrosinase, and melanocytes lose the ability to synthesize melanin.
2. Autoimmune theory Vitiligo patients or their families often have other autoimmune diseases, such as thyroid disease, insulin-dependent diabetes, chronic atrophic gastritis, psoriasis, alopecia areata, lupus erythematosus, etc. Compared with normal people, the positive rate of organ-specific antibodies in the serum of vitiligo patients is also significantly increased, such as anti-gastric parietal cell antibodies, anti-adrenal globulin antibodies, and anti-adrenal tissue antibodies. It has been confirmed that vitiligo patients contain autoantibodies against melanocytes in their serum, with a positive rate of 27% to 93%, and the positive rate and titer of antibodies are closely related to the activity of the disease.
3. Neuropsychiatric theory Melanocytes originate from the neural crest, and the common clinical skin lesions of this disease are symmetrical or segmental
distribution. Postoperative and mental trauma can induce the occurrence of this disease. It is generally believed that mental stimulation can lead to increased activity of the monoamine system, thereby leading to an increase in norepinephrine, epinephrine or other catecholamines, indicating that the onset of vitiligo is related to the nervous system. The B-endorphin level in the plasma of patients with vitiligo is significantly increased, and the B-endorphin level in the tissue fluid of localized and segmental types is also significantly higher than that of unaffected skin, indicating that B-endorphin may be involved in the onset of vitiligo. 4. Melanocyte self-destruction theory This disease often occurs in exposed and pigmented areas. Some people believe that it is due to the hyperfunction of epidermal melanocytes, which promotes their consumption and early decline, and may be caused by the excessive production or accumulation of intermediates such as dopa and 5,6-dihydroxyindole in the synthesis of melanin by the cells themselves. Experiments have shown that phenols and catecholamines have a damaging effect on normal or malignant melanocytes, leading to the occurrence of vitiligo. 5. Theory of relative deficiency of tyrosine and copper ions The copper or ceruloplasmin levels in the blood and skin of patients with vitiligo are reduced, resulting in reduced tyrosinase activity, thereby affecting the metabolism of melanin. In addition, certain chemicals and photosensitive drugs can also induce this disease.

II. Clinical manifestations

1. Clinical manifestations Vitiligo is acquired, with no obvious gender differences. It can occur at any age, but is more common in young and middle-aged people. About 50% of patients develop the disease before the age of 20. Some patients have obvious seasonality. Generally, the disease progresses more severely in late spring and early summer, and eases in winter. It can occur on any part of the skin, but it is more likely to occur in exposed and frictional areas, such as the face, neck, back of the hand, wrist, forearm and lumbar sacral area. The lips, labia, glans penis and inner mucosa of the foreskin can also be involved. In some patients, white spots are distributed unilaterally along the nerve segments, and in a few patients, the skin lesions are widespread throughout the body. When the skin lesions first occur, they are one or several hypopigmented spots with unclear boundaries, which gradually expand into clearly depigmented spots with milky white color. Scattered island-shaped pigment areas around the pores may appear in the white spots. The hair in the white spots can turn white or be normal. Those who develop on the head may only have white hair without white spots. Most patients have no subjective symptoms. The course of the disease is chronic and sometimes improves or disappears on its own. During the progression of the disease, white spots may migrate to normal skin. Sometimes mechanical stimulation such as pressure, friction, burns, and trauma may also cause vitiligo (isomorphic reaction). In the stable stage, the skin lesions stop developing and appear as clearly depigmented spots with increased pigmentation at the edge of the lesions.
2. Classification: According to the range and distribution of skin lesions, the disease can be divided into common type and segmental type.
(1) Common type: It is further divided into scattered type, generalized type, facio-acral type and mucosal type.
① Scattered type: white spots are scattered, of varying sizes, but mostly distributed symmetrically.
② Generalized type: It often develops from localized or sporadic type, and the total area of ​​white spots is greater than 50% of the body surface area.
③ Facio-acral type: skin lesions are distributed on the face and distal limbs.
④ Mucosal type: skin lesions only affect the mucosa.
(2) Segmental type: The skin lesions are distributed according to the dermatome or a certain nerve distribution area.

III. Pathological characteristics

In addition to the decrease or disappearance of the number of basal melanocytes and melanin granules, vitiligo tissue pathology generally has no inflammatory reaction. Vitiligo patients have reduced or absent melanosomes and melanocytes in the basal cell layer. In the active stage of the lesion, the density of melanocytes in the center is surrounded by abnormally enlarged melanocytes, which is 2 to 1/2 times that of the normal area in the edge area. In the early inflammatory stage, epidermal edema and sponge formation can be observed at the so-called raised edge of vitiligo, and lymphocyte and tissue cell infiltration can be seen in the dermis. The main change in the established vitiligo lesions is the reduction or even disappearance of melanosomes in melanocytes. There are no melanocytes in the late depigmented lesions.

IV. Diagnosis and differential diagnosis

It is not difficult to diagnose this disease based on clinical manifestations. However, it needs to be differentiated from the following diseases. Learning without cold food will make you wise
(I) Simple pityriasis Simple pityriasis is common in children, with localized hypopigmented spots on the face, rather than depigmented spots, and unclear boundaries of the lesions, and often fine scales on the surface.
(II) Pityriasis versicolor
Pityriasis versicolor lesions often occur on the neck, trunk, and upper limbs. They are round or oval light-colored spots with many scales on the surface. Fungi are easy to find in the lesions.
(III) Anemic nevus
Anemic nevus is a congenital hypopigmented spot, generally distributed unilaterally. Due to the sparse capillaries in the lesion area, the skin around the white spot is congested after friction or heating, but the white spot itself does not turn red, which can be distinguished from vitiligo. (IV) Pigmented spots
Pigmented spots are localized light-colored spots that appear at birth or shortly after birth. They are often distributed along the nerve segments, with blurred boundaries and no pigmentation bands around them. They are generally single and last for life. (V) Post-inflammatory hypopigmentation
Post-inflammatory hypopigmentation has a history of primary disease, such as eczema, dermatitis, psoriasis, etc. The hypopigmentation is limited to the skin lesions of the primary disease, is generally temporary, and can recover on its own.

V. Treatment

The main purpose of the treatment of this disease is to control the progression of skin lesions and promote the restoration of white spots. The selection of treatment measures mainly considers the area, type, location, age, and course of the disease. The principle of treatment is to treat as early as possible and adopt personalized comprehensive therapy (combination of Chinese and Western medicine, combination of external and internal drugs, combination of drugs and physical therapy, combination of drugs and physical therapy and surgical treatment) according to different patients as much as possible. Treatment should be long-term, and each course of treatment should last at least 3 months.
(I) Glucocorticoid treatment
Topical glucocorticoid treatment is suitable for skin lesions with white spots of less than 10% area. Use super-potent or potent hormones. The best treatment areas are the face and neck, but attention should be paid to the adverse reactions of long-term use of hormones. Currently, calcineurin inhibitors are mainly recommended for skin lesions on the face and neck.
Systemic glucocorticoid treatment is mainly suitable for patients with generalized rapidly progressive vitiligo. A small dose of prednisone can be taken orally at 0.3 mg/kg per day for 1.5 to 3 months, and then discontinued if ineffective. After the effect is achieved, the dosage is gradually reduced by 5 mg every 2 to 4 weeks to 1 tablet every other day, and maintained for 3 to 6 months. Or compound betamethasone 1 mL, intramuscular injection, once every 20 to 30 days, can be used 1-times. Due to its many adverse reactions, long-term systemic hormone treatment is not recommended. Generally, for patients with rapid progression, in order to control the disease as soon as possible, the dosage is usually doubled in the first 3 days, and the dosage is reduced and stopped earlier. After the disease progression is quickly controlled, treatment is continued with traditional Chinese medicine and immunomodulators.

(ii) Calcineurin inhibitors
Topical calcineurin inhibitors include tacrolimus ointment and pimecrolimus cream. The treatment time is 3 months to 1 year. The best areas for repigmentation are the face and neck. It can also be used on mucous membranes and genitals. (iii) Vitamin D derivatives
Topical calcipotriol and tacalcitol can be used to treat vitiligo in adults, applied twice a day. Vitamin D can be combined with NB-UVB, 308 excimer laser, PUVA, etc., or combined with topical hormones and calcineurin inhibitors. Topical calcipotriol or tacalcitol can enhance the efficacy of NB-UVB in treating vitiligo. Since calcipotriol and tacalcitol have photoprotective effects against UVA and UVB, it is recommended to use them at night 1 day before phototherapy.
(iv) Traditional Chinese medicine-generally adopts disease differentiation combined with syndrome differentiation, which is divided into two stages: progressive stage and stable stage, forming four main syndrome types corresponding to them (rheumatism and heat syndrome, liver depression and qi stagnation, liver and kidney deficiency syndrome, blood stasis and obstruction syndrome). The progressive stage is characterized by rheumatism, heat depression, liver depression and qi stagnation, and the stable stage is characterized by liver and kidney deficiency and blood stasis. Children often show weakness of spleen and stomach. In terms of treatment, the progressive stage is mainly to dispel evil, dispel wind, clear heat and dampness, and relieve liver depression; the stable stage is mainly to nourish the liver and kidney, promote blood circulation and remove blood stasis, and select the corresponding meridian-guiding medicine according to the site.
(V) Phototherapy and photochemotherapy (PUVA) Phototherapy includes high-energy ultraviolet light, helium-neon laser, NB-UVB, 308nm excimer laser and excimer light. Because high-energy ultraviolet light has poor efficacy, normal skin pigmentation time is too long, and the efficacy of helium-neon laser is uncertain, with the use of NB
UVB in the clinical treatment of vitiligo, these two types of light are gradually eliminated in the treatment of vitiligo. 1. Narrow-band UVB (311nm) wavelength range 310~315nm, peak wavelength 311nm. Its mechanism of treating vitiligo may be to promote the release of endothelin-1, 1-1a, basic fibroblast growth factor (bFGF) by keratinocytes, and to increase the expression of melanocyte tyrosinase. In addition, narrowband UVB can also inhibit the immune function of skin dendritic cells and T lymphocytes. Compared with traditional PUVA, it has the advantages of high safety and fewer side effects. Systemic NB-UVB treatment is suitable for patients aged >9 years with vitiligo involving an area of ​​>20%. It can also be used for children aged <9 years who are in the progressive stage of widespread skin lesions and can closely cooperate with the treatment.
The treatment steps of narrowband UVB are as follows:
(1) Precautions before treatment: The operator wears ultraviolet protective glasses during treatment. If the lesions are around the eyes, ask the patient to close his eyes; if the whole body is irradiated, ask the patient to wear shorts to protect the reproductive parts.
(2) Treatment method: The initial dose is 70% of the minimum erythema dose. According to the photosensitivity classification, Chinese people are mainly subtype and type I skin. The first dose of the former is 0.3~0.5J/cm', and the latter is 0.5~0.7J/cm'. Exposure is given twice a week. In the initial stage of treatment, the dose is increased by 20%~50% each time. After the appearance of light erythema, the dose is generally increased by 0~20% each time. The final single dose does not exceed 3.0J/cm'. (3) Precautions after treatment: During treatment, patients are advised to avoid direct sunlight on the body surface and apply sunscreen to the exposed area. Some patients may develop photosensitivity to NB-UVB. The number of treatments and the course of treatment depend on individual photosensitivity (if the area of ​​the pigment island does not increase after continuing phototherapy, photosensitivity is considered to be produced). After tolerance occurs, you can rest for 3~6 months before continuing treatment.
2.308nm excimer laser Excimer laser refers to a continuous pulsed gas laser generated by an excited dimer. The dimer is composed of an inert gas and a halogen gas mixed in a certain proportion and pressure in atomic form. When the current passes through, the activated inert gas and halogen gas can form halides and release monochromatic light of a specific wavelength. 308nm excimer laser, also known as XeCI excimer laser, is a dimer composed of inert gas xenon and halogen chlorine that releases ultraviolet light with a wavelength of 308nm after being excited. The spot diameter of 308nm excimer laser is adjustable, with an adjustment range of 218mm. The energy of each pulse can reach 3~5.5mJ/cm', and the deepest can penetrate up to 1.5mm of the superficial dermis.
The mechanism of 308nm excimer laser treatment of vitiligo is not clear, and may include the following two aspects: ① Inducing apoptosis of activated T lymphocytes in the lesion, which can directly promote apoptosis of pathological T lymphocytes; it can also act on keratinocytes, causing the former to produce cytokine TGF-B1 and indirectly induce lymphocyte apoptosis. ② Stimulate melanocyte proliferation and promote melanin production, by promoting the proliferation of non-pigmented melanocytes in the outer root sheath of hair follicles that are not involved to produce melanin and migrate to the white spots.
Indications: Suitable for the treatment of patients with stable local vitiligo with skin lesions less than 30% in area. Combined with topical tacrolimus or pimecrolimus, etc., its efficacy can be improved. Compared with the currently commonly used treatment methods, the advantages of 308nm excimer laser in the treatment of stable vitiligo are: ① The instrument is flexible to operate and has advantages in the treatment of focal lesions, especially wrinkles. ② The 308nm excimer laser has high energy and rapid effect, and can also reduce the total accumulation of ultraviolet rays in the skin. ③ The 308nm excimer laser acts on the skin lesions in the form of spot output, which does not affect the surrounding normal skin and can reduce the probability of aging of the surrounding skin and skin cancer.
The treatment operation steps of 308nm excimer laser are as follows:
(1) Preparation before treatment: During treatment, apply sunscreen around the skin lesions or use sunscreen to protect normal skin. The treatment staff uses protective glasses and the patient closes his eyes to protect his eyes. The treatment is painless, so epidermal anesthesia is not required, and no coupling agent cold gel is required. Clean the treatment area and disinfect it with Sanisol.
Select the patient's upper buttocks or lower back of normal skin that is not sunburned for the minimum irradiation dose (MED) test. Select the initial dose based on the MED test results.
(2) Treatment dose: The initial treatment dose (ID) is determined according to the MED and the location of the skin lesion. It is generally 0.5~1MED, and different initial treatment doses are selected according to different locations. The subsequent irradiation dose depends on the reaction of erythema in the skin lesion after the previous irradiation. If the erythema lasts less than 24 hours, the treatment dose is increased by 50~100mJ/cm'', and 25~50mJ/cm' for children. If the erythema lasts for 24~48 hours, the treatment dose remains the same as the previous one. If the erythema lasts for 48~60 hours, the treatment dose is reduced by 50~100mJ/cm?, and 25~50mJ/cm? for children. If the erythema lasts for 60~72 hours or obvious blisters, burning pain, etc. appear, the treatment time is postponed accordingly until the above symptoms basically subside, and the next treatment dose is reduced by 100mJ/cm'.
(3) Treatment frequency: 1 to 3 times a week, 2 times a week is more common, with an interval of 3 to 4 days between each treatment. This can achieve results quickly without causing side effects due to too frequent treatment. Some patients are combined with 3% tacrolimus cream due to slow pigment growth. Most patients need 10 to 50 treatments, with an average of 35 times. Generally speaking, the treatment effect on the face should be better than on the trunk and limbs, and on the trunk and limbs better than on the extremities.
(4) Postoperative precautions: Most of the reactions such as burning sensation, erythema, and blisters in the treatment area are relatively mild. Generally, no special treatment is required. Avoid rubbing the treatment area. If necessary, give corresponding treatment to prevent infection. The treatment area should be protected from the sun. 3. Photochemotherapy (PUVA) Photochemotherapy is a method of combining photosensitizers and long-wave ultraviolet rays (ultraviolet rays of 320 to 482 nm) to treat diseases. Its possible mechanism is: stimulating vitiligo

Source: Vitiligo