311nm NB-UVB Phototherapy--Treatment of Vitiligo

What is "phototherapy"

Phototherapy is a method that uses electromagnetic radiation to produce light of different wavelengths to treat skin diseases. Phototherapy is the oldest and most effective physical method to treat skin diseases. As early as the ancient Greek period, there were written records of the use of sunbathing to treat skin diseases, but it was not until the beginning of the 20th century that systematic research on the mode of phototherapy began.

According to the wavelength, people divide electromagnetic waves into radio waves, infrared rays, visible light, ultraviolet rays, X-rays, and gamma rays.

In this spectrum, electromagnetic waves with a wavelength of 200-400nm are called "ultraviolet rays" and are invisible to the naked eye. Ultraviolet rays are divided into three bands according to the length of the wavelength: long-wave ultraviolet (UVA, wavelength 320-400nm), medium-wave ultraviolet (UVB, wavelength 280-320nm), and short-wave ultraviolet (UVC, wavelength 200-280nm). At present, the electromagnetic wave bands used in the treatment of vitiligo are mainly long-wave ultraviolet (UVA) and medium-wave ultraviolet (UVB), especially one of the narrower bands-narrow-band medium-wave ultraviolet (NB-UVB, which is often referred to as 311nm light), and 308nm excimer laser (referred to as 308-nanometer laser), are located in the mid-wave ultraviolet band. Today let's learn about how is the NB-UVB cure vitiligo.

This is a picture of the epidermis structure. From the picture, we can see that in the lowermost layer of the epidermis, the cells that are relatively large and have many branch-like branches are the melanocytes of the epidermis. Under normal circumstances, melanocytes synthesize melanin particles and transport them to neighboring epidermal cells (called "keratinocytes") to maintain normal skin color. At the same time, keratinocytes can synthesize specific cytokines to promote the growth of melanocytes. In the epidermis, a melanocyte and 36 adjacent keratinocytes form an organic whole, called "epidermal melanin unit".

Vitiligo is a common depigmented skin disease with no ethnic differences, and its pathogenesis has not been fully studied.

Light therapy is widely used as the first-line treatment for vitiligo. Narrow-band UVB (NB-UVB) is characterized by polychromatic light with a peak wavelength of 311~313nm. Compared with psoralen photochemotherapy (PUVA), the eyes do not need shading protection after NB-UVB treatment, which is phototoxic. Less reaction, not easy to burn the skin and cause DNA mutations. Adverse reactions such as dry skin, itching, and photoaging after treatment are related to the number of treatments, frequency, amount of erythema, and cumulative dose.

Studies have shown that NB-UVB can promote the recovery of vitiligo pigments in the following ways:

1. Vitiligo patients have abnormal lymphocytes that can destroy melanocytes. Ultraviolet rays can induce apoptosis of these "bad cells", thereby protecting melanocytes from damage.

2. After UVB irradiation, pseudo catalase can be activated, which can quickly degrade hydrogen peroxide (H2O2) into water and oxygen, and protect melanocytes from oxidative damage.

3. Ultraviolet rays can directly stimulate the proliferation and migration of melanocytes and increase the synthesis of melanin.

4. Ultraviolet rays can promote keratinocytes to release factors that promote the proliferation of melanocytes and increase the number and functions of melanocytes.

311nm NB-UVB treat principle

1. Induce the differentiation of hair follicle neural crest stem cells:

Hair follicles act as skin appendages, regulate hair growth and shedding, and have sensory and immune functions. The bulge area of the hair follicle is the area where the upper part of the outer root sheath of the hair follicle bulges outward. The neural crest is a longitudinal cell band between the epidermis and the neural tube during the formation of the neural tube. Neural crest stem cells (HF-NCSCs) exist in the bulge area of hair follicles. Melanocytes originate from HF-NCSCs, migrate along the neural tube to the ganglia, differentiate into melanocyte stem cells, and then differentiate into melanocytes in the ectoderm.

The pigment regeneration induced by NB-UVB is mainly achieved through the recoloring mode around the hair follicle. NB-UVB irradiation can accelerate the differentiation of NCSCs cultured in vitro into melanocytes, but the phenomenon of recoloring is not observed in the depigmented area. Therefore, NB-UVB stimulates the differentiation of HF-NCSCs in the bulge region of the outer root sheath of the hair follicle into melanocytes, thereby promoting the proliferation and migration of melanocytes.

2. Perform immunomodulation:

(1) Affect T cell function: The dysfunction of Tregs may be one of the factors that destroy the tolerance to the autoantigens of melanocytes and contribute to the pathogenesis of vitiligo. NB-UVB may improve the function of Tregs by adjusting the number of Tregs in the circulation, and inhibit the destruction of Tregs to the autoantigen tolerance of melanocytes.

(2) Regulating immune factors: The level of IL-17A in the serum of patients with generalized vitiligo treated with NB-UVB decreased, indicating that NB-UVB treatment can reduce the secretion of IL-17A. However, the potential mechanism of NB-UVB on these cytokines is not fully understood. Its immunomodulatory effect may be through influencing T cell aggregation, reducing inflammation infiltration, and then affecting the serum level of cytokines.

3. Regulate the microenvironment of melanocytes: The secretion of ET-1 in the KC culture medium irradiated by NB-UVB increased significantly and was proportional to the irradiation dose, while the melanocytes (MC) cultured in vitro showed no significant changes. It indicates that NB-UVB may stimulate melanin production through keratinocytes. NB-UVB irradiation can also increase the level of phosphorylation (p- 125FAK), stimulate the secretion of mitogen (bFGF), and enhance the migration ability of melanocytes.

4. Induce the synthesis of endogenous vitamin D: Vitamin D increases the melanogenesis and tyrosinase content of MC by anti-apoptotic effect to control its activation, proliferation and migration, and reduces the autoimmune damage of melanocytes by regulating T cell activation. Studies have shown that compared with normal serum, patients with vitiligo have significantly lower serum 25( OH) D levels. After 12 weeks of NB-UVB treatment, the level of serum 25〔OH〕D was positively correlated with the expression of VDR. These findings indicate that NB-UVB is related to vitamin D synthesis and VDR expression.

The mechanism of action of NB-UVB in the treatment of vitiligo involves a variety of biological effects, including induction of hair follicle HF-NCSCs differentiation, immune regulation and regulation of the melanocyte microenvironment, and induction of endogenous vitamin D synthesis.

In recent years, more and more attention has been paid to the application of 308 nm excimer laser in vitiligo scenery treatment. 308 nm excimer laser has better curative effect on vitiligo with small white spot area and small number, while NB-UVB is more suitable for sporadic or generalized types of vitiligo. Treatment of vitiligo.