The Pigmentology Group of the Chinese Society of Integrative Medicine and Dermatology organized 16 members of the Pigmentology Group and related experts in China to develop the Revised Consensus on Vitiligo Treatment (2009 Edition) based on the Revised Consensus on Vitiligo Treatment (2005 Edition) after repeated discussions. We believe that the guidelines will be of great importance to the dermatologists and general practitioners who have been working in the outpatient clinics for a long time.
First of all, let’s talk about the necessity of developing the guidelines. As we all know, vitiligo is a common acquired, refractory pigmentary disorder that manifests as pigment loss in different degrees in the skin, hair and mucous membrane areas. This is a very good way to get the most out of your life. The prevalence of vitiligo is about 1%. The results of a survey conducted by our department for six different regions in China showed that the total prevalence in our country was 0.553% [2]. Considering the large population in our country, the number of vitiligo patients should be considerable. Over the years, the academic community has conducted extensive and in-depth research on the pathogenesis and treatment measures of vitiligo, although the cause and pathogenesis of vitiligo are still not completely clear, but the treatment measures about vitiligo have made great progress in the last 10 years, such as new immunosuppressants, various phototherapy, surgical therapy, etc. have achieved good efficacy in the clinical treatment of vitiligo. But regrettably, many patients are eager to seek medical treatment, often the whole family out according to the advertising, publicity and so on throughout the country, the size of the hospital, clinics everywhere to seek medical treatment, the result is the treatment is not regular, the money did not spend less, but the effect is not satisfactory. Some dermatologists and general practitioners also have limited knowledge of the disease, and treatment is not standardized, and they do not even choose the treatment plan according to the patient’s age, stage, type and severity of the disease, which affects the patient’s efficacy and even aggravates the disease. There are also individual doctors who believe that this disease is difficult to cure and advise patients to give up treatment. Considering the huge impact of vitiligo on patients themselves and their families, as dermatologists and general practitioners, we should actively face this disease, not only to treat vitiligo, but also to give reasonable treatment to patients earlier and more actively. And the current status of vitiligo treatment is that there are large differences between different dermatologists and related medical practitioners for vitiligo treatment, some treatments lack literature support and some are even harmful to patients, so there is a special clinical need for a set of practical guidelines to regulate vitiligo treatment for the best treatment results.
Before introducing the content of the guidelines, we briefly introduce the possible pathogenesis of vitiligo and the clinical typing and staging of vitiligo. Vitiligo is clinically manifested by different degrees of pigment loss in the skin, hair and mucous membrane areas, while the pathology shows reduced or even complete absence of melanocytes and melanin in the leukoplakic areas. The cause of melanocyte deficiency is still unclear, and there are more theories about the pathogenesis of vitiligo, including autoimmune theory, genetic theory, melanocyte self-destruction theory, cytokine deficiency theory, neurochemical theory, oxidative stress theory and so on. Although it is difficult to explain the onset of vitiligo by one mechanism alone, several studies have shown that autoimmune abnormalities are an important factor in the onset of vitiligo and melanocyte deficiency, and this theory has been widely recognized by the academic community. First of all, vitiligo patients do have abnormalities in specific humoral and cellular immune functions. Studies have shown that specific antibodies against melanocyte surface antigens are present in the serum of vitiligo patients and correlate with the size and activity of the lesions [3-4].Ongenae et al [5] also showed that autoantibodies against MC membrane or intracytoplasmic antigens (anti-tyrosinase antibody, tyrosinase-associated protein 1 antibody, tyrosinase-associated protein 2 antibody) are present in the serum of vitiligo patients. In addition, in addition to abnormalities in humoral immune function, there are also abnormalities in cellular immune function in vitiligo. Studies have shown significant lymphocyte infiltration around active lesions with CD8+ cytotoxic T cell infiltration around the lesions [6].Palermo et al [7] found specific cytotoxic T cell responses against MelanCA, MART1, and tyrosinase in the sera of vitiligo patients, and these MC-specific CD8+ T cells have the ability to destroy MC in vitro. Mahmound et al [8] applied flow cytometry to count T cells in the serum of 34 patients with non-segmental vitiligo and found that the number of CD25 and HLA-DR positive cells was significantly higher in the patients, suggesting the involvement of activated T cells in the pathogenesis. Li Dongning et al [9] found that CD3 and CD4 levels were decreased and CD8 levels were increased in patients with common progressive vitiligo. All these studies suggest that abnormal cellular immunity may be involved in vitiligo pathogenesis. Clinical studies have also found that the occurrence of other autoimmune diseases in vitiligo patients and vitiligo in patients with other autoimmune diseases is significantly higher than the general population. A variety of organ-specific autoantibodies can also be measured in the serum of vitiligo patients. Some vitiligo patients have a combination of hyperthyroidism, thyroiditis, diabetes mellitus, pernicious anemia, Addison’s disease, baldness, ulcerative colitis, systemic lupus erythematosus, dermatomyositis and other autoimmune related diseases, the most common of which is thyroid disease [10-12]. The above immune abnormalities in vitiligo help us to understand why corticosteroids, new immunosuppressants, phototherapy and other methods with immunosuppressive effects can be used clinically to treat vitiligo. Of course, in specific treatment we should also individualize and rationalize the treatment according to the patient’s condition, age, lesion site, stage, typing, and general condition.
The clinical staging and typing of vitiligo is very important, which will help us to choose the treatment plan and evaluate the efficacy. First of all, vitiligo can be divided into progressive and stable stages according to the progress of the patient’s condition. The progressive stage is determined by the VIDA score (Vitiligo Disease Activity Score): new lesions or enlarged original lesions within the last 6 weeks +4; new lesions or enlarged original lesions within the last 3 months +3; new lesions or enlarged original lesions within the last 6 months +2; new lesions or enlarged original lesions within the last 1 year +1; stable for at least 1 year 0 A total score greater than 1 is considered progressive. Secondly, according to the vitiligo lesion distribution type, location, area, etc. vitiligo is divided into two types: common type and segmental type. The most common type of vitiligo is the one that is confined to a certain area; the epidemic type is the one that is scattered and distributed symmetrically and the total area does not exceed 50% of the body surface area; the generalized type is the one that is generalized and involves more than 50% of the body surface area; and the limb type is the one that is mainly distributed on the limbs and face. The nodal type is the distribution of lesions along the nerve segments, rapid development within two years of onset, after which most patients lesions are stationary and remain unchanged for life.
The appendix is the 2009 version of the vitiligo treatment consensus developed by the expert group according to the above vitiligo stage, typing and many other factors. I personally think the 2009 version of the consensus has four major features, first, the consensus especially emphasizes the importance of early diagnosis and early treatment of vitiligo with a view to achieving better treatment results. The first is the importance of early diagnosis and early treatment of vitiligo in order to achieve better treatment results. The third, in view of the vitiligo etiology and pathogenesis is unknown, the efficacy and side effects of various treatment methods are different, the consensus proposed treatment should be taken as far as possible integrated therapy (combination of Chinese and Western medicine, combination of external and internal medicine, combination of medicine and physical therapy, combination of medicine and physical therapy and surgical therapy). And patients should be instructed that treatment should be adhered to for a long period of time, with a course of treatment lasting at least 3 months. Fourthly, the 2009 version of the consensus has added many new methods for the treatment of vitiligo compared with the 2005 version, such as topical calcium-modulated neurophosphatase inhibitors, various phototherapy and surgical treatment, and the scope of application, specific methods, precautions and common adverse reactions of each treatment method are described in detail in the rules, and the practicality of clinical application is much stronger. The above features will be discussed below.
The early diagnosis and early treatment of vitiligo is very important. Generally speaking, early vitiligo treatment is good, the treatment effect of long duration of the disease will be relatively poor. And once the diagnosis of vitiligo is established, the next step is to develop a personalized and comprehensive treatment plan for the patient, and emphasize that the course of treatment should be sufficient, at least 3 months or more. In the development of the program, the consensus proposes to first determine whether the patient’s disease stage is stable or progressive, and then combine the different clinical staging to determine the program. For example, the consensus suggests that for progressive vitiligo, if it is limited type, topical treatment can be given, such as topical glucocorticoids (hormones) or calcium-regulated neurophosphatase inhibitors (tacrolimus, pimecrolimus); local phototherapy can be chosen from narrow-spectrum medium-wave ultraviolet light (NB-UVB), 308 nm excimer laser and excimer light, high-energy ultraviolet light. For patients with progressive epidemic, pancytopenia and acromegaly, in addition to local treatment, Chinese herbal medicine and immunomodulators can also be added, and systemic glucocorticoids are considered for VIDA score >3. And for stable patients, the consensus suggests that autologous epidermal transplantation or melanocyte transplantation can be used for treatment.
In clinical work for the consensus in the mastery of the general principles is very important, on the basis of the general rules can develop a reasonable and effective program for patients. However, the general case is only a framework, and many details need to be paid attention to in the specific implementation, so the 2009 version of the consensus has increased a lot of space in the rules to facilitate the practical application of clinical workers. The treatment rules firstly give guidance on the hormonal treatment of vitiligo, such as topical topical hormones are suitable for progressive lesions with <10% of the involved area of white spots. The topical hormone can be used continuously for 1-3 months or under the guidance of a specialist, or alternately with strong or weak hormones or weak or medium hormones. For adults, topical application of strong hormones is recommended. If there is no recoloration after 3-4 months of continuous topical hormone treatment, it indicates poor efficacy of hormone treatment and needs to be replaced by other topical treatment methods. And systemic hormone is mainly applied to patients with generalized progressive vitiligo. The adult progressive vitiligo can be small doses of oral prednisone 0.3 mg/kg/d for 1 to 3 months, discontinued. After the effect, the dose is reduced by 5 mg every 2-4 weeks to 5 mg every other day for 3-6 months. Or compound betamethasone 1 mL, intramuscular injection, once every 20-30 days, available l-4 times. Of course, the hormone should be applied flexibly in the clinic according to the patient's efficacy and adverse reactions. The rules also provide detailed descriptions of various phototherapy and photochemotherapy such as irradiation dose, frequency, dose adjustment methods, precautions, contraindications, etc., which facilitate clinical control and use and are worth reading carefully. The rules add topical calcium-regulated neurophosphatase inhibitors including tacrolimus ointment and pimecrolimus cream for the treatment of vitiligo, providing patients with more treatment options. The rules state that these topical medications have no side effects caused by hormones, especially strong hormones, but attention should be paid to possible increased local infections such as folliculitis. The rules also describe depigmentation therapy, but it should be emphasized that this method is only applicable to white spots involving >95% of the area, resistant to various methods of repigmentation therapy, and can only be used at the request of the patient.
In the clinic work, we often encounter children vitiligo patients, do not know how to treat. The common sense has made a special guidance on this, suggesting that for children <2 years old with limited leukoplakia can be treated with intermittent topical medium potency hormones, and children >2 years old can be treated with topical medium or strong potency hormones. In addition topical calcium-regulated neurophosphatase inhibitors tacrolimus ointment and pimecrolimus cream can also be used for the treatment of vitiligo in children >2 years of age. The most difficult clinical rules for rapidly progressive vitiligo in children are recommended to be treated with small doses of hormones orally, and oral prednisone 5-10mg/d for 2-3 weeks is recommended. If necessary, the treatment can be repeated again after 4-6 weeks.
The rules also emphasize that while giving patients reasonable and effective treatment, patients should be encouraged to release their worries, build up confidence and adhere to the treatment, and be instructed to pay attention to avoid trauma and exposure to the sun, especially in the progressive stage. In addition to the treatment of vitiligo, patients should also pay attention to the treatment of accompanying diseases, such as the autoimmune diseases mentioned earlier. Also supplementation with vitamin B, vitamin E, folic acid, zinc, calcium, selenium, etc. may be helpful in vitiligo treatment.
The note at the end of the consensus is also important and should be read carefully. Considering the complexity and refractory nature of the disease, the consensus emphasizes that treatment may follow this treatment guideline but does not guarantee satisfactory outcome for all patients, and in addition the treatment guideline does not include all current treatments for vitiligo. In addition, some drugs (such as tacrolimus, pimecrolimus, carboplatinol, etc.) are not included in the drug descriptions for vitiligo, but there is a large body of literature from home and abroad that proves that these drugs are effective for vitiligo. These additional instructions can help doctors communicate better with patients and relieve their concerns.
In conclusion, as long as we carry out reasonable, effective and safe individualized treatment according to the guidelines and the specific conditions of vitiligo patients, most vitiligo patients can get better results and regain their beautiful complexion.
References [1] Pigmentology Group of the Professional Committee of Dermatological Venereal Diseases of the Chinese Society of Integrative Medicine. Revised consensus on vitiligo treatment (2009 edition). Chinese Journal of Dermatology,2009,42(9):591-593 [2] Wang Xiaoyan, Wang Tinglin, Zhou Cheng, et al. Epidemiological survey of vitiligo in six Chinese provinces and cities. Chinese Journal of Dermatology. 2010; 43(7):463-466. [3] Naughton GK, Reggiardo D, Bystryn JC. Correlation between vitiligo antibodies and extent of depigmentation in vitiligo J Am Acad Dermatol. 1986 Nov;15(5 Pt 1):978-981 [4] Farrokhi S, Hojjat-Farsangi M, Noohpisheh MK, et al. Assessment of the immune system in 55 Iranian patients with vitiligo. J Eur Acad Dermatol Venereol 2005;19(6):706C711. [5] Ongenae K, Van Geel N, Naeyaert JM. Evidence for an autoimmune pathogenesis of vitiligo. Pigment Cell Res, 2003, 16(2): 90-100. [6] Kawakami Y, Suzuki Y, Shofuda T, et al. T cell immune responses against melanoma and melanocytes in cancer and autoimmunity. Pigment Cell Res. 2000; 13 Suppl 8:163-169. [7] Palermo B , Campanelli R , Garbelli S , et al. Specific cytotoxic T lymphocyte responses against Melan-A/MART1, tyrosinase and gp100 in vitiligo by the use of major histocompatibility complex/peptide tetramers: the role of cellular immunity in the etiopathogenesis of vitiligo.J Invest Dermatol, 2001,117(2):326-332. [8] Mahmoud F, Abul H, al-Saleh Q, et al. Peripheral T-cell activation in non-segmental vitiligo. J Dermatol,1998,25(10):637-640. [9] Li DN ,Pei HJ,Zhou HQ et al. Detection of T-cell subsets in peripheral blood of patients with vitiligo. Chinese Journal of Dermatologic Venereology, 2006, 20(7):420-421. [10] Zhu Tiejun. Clinical study of 650 cases of vitiligo. Journal of Clinical Dermatology,1995,24(5):279-282. [11] Zhou PY, Zhu HQ, Han JJ. Vitiligo complicated by disseminated discoid lupus erythematosus. Journal of Clinical Dermatology, 2006 , 35 (7):463-464. [12] Yang XQ, Du Y, Deng M et al. The correlation between vitiligo and autoimmune thyroid disease. Chinese Journal of Dermatologic Venereology, 2007, 21,(1):26-27.