Comprehensive survey of vitiligo patients in the northeast of China using a predesigned questionnaire

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1 doi: / Journal of Dermatology 18; 4: 39 4 ORIGINAL ARTICLE Comprehensive survey of vitiligo patients in the northeast of China using a predesigned questionnaire Zheng LIN, 1 Yaping TIAN, 2 Bingxue BAI, 3 Mei LIU, 1 Yan WU, 1 Bihuan XIAO, 1 Xing-Hua GAO, 1 Hong-Duo CHEN 1 1 Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang, 2 Department of Dermatology, No. 1 Hospital of Jilin University, Changchun, 3 Department of Dermatology, No. 2 Hospital of Harbin Medical University, Harbin, China ABSTRACT To assess the sociodemographic data and clinical information of outpatients affected by vitiligo in the northeast of China, vitiligo patients or guardians who presented to the clinic were invited to participate in an exploratory questionnaire. The questionnaire consisted of two sections related to vitiligo, including sociodemographic data and clinical information. A total of 983 vitiligo patients answered the questionnaire. The rates of female and male patients were comparable. The investigated patients were mostly young and middle-aged. Most patients suffered from vitiligo in childhood or young adulthood. Vitiligo vulgaris was the most common type of vitiligo in clinic and 3.% of patients were categorized as body surface area (BSA) of 1% or less. In response to the latest treatment, 43.6% of patients achieved good response (completely stopped or almost disappeared). More patients at active stage showed good response than the patients at stable stage (v 2 = 7.866, P <.). Chronic comorbid condition(s) were observed in 12.6% of patients with BSA of more than 1%, whereas those were seen in 6.% of patients with BSA of 1% or less (v 2 = , P <.). In conclusion, active vitiligo seems to respond better than stable vitiligo and complications with other autoimmune diseases more frequently observed in severe patients than mild patients. The current study presented a comprehensive understanding of vitiligo in the northeast of China. Key words: clinical information, questionnaire, sociodemographic data, treatment, vitiligo. INTRODUCTION Vitiligo is a chronic skin disease characterized by depigmentation of the skin which affects all races and both sexes. 1 The prevalence is.1 2% in different communities. 2 Manifestations can occur at any age. 3 However, in half of these patients, the disease manifests itself before the age of years. 4 The pathogeny of vitiligo is unknown. Various pathogenetic mechanisms have been suggested, including genetic association, cellular and humoral autoimmunity, oxidative stress, neurohormonal imbalance, abnormalities in the microenvironment surrounding the melanocytes and intrinsic defects of melanocytes.,6 Vitiligo lesions are frequently noted on sun-exposed areas, normally hyperpigmented areas, and areas prone to repeated friction and trauma, without discernible preceding erythema or pruritus. 7 Various therapies are available, depending on the localization and the extent of lesions. However, vitiligo treatment is usually prolonged with unsatisfactory outcomes as there are no optimal methods which lead to complete repigmentation of the depigmented lesions Conventional medical treatments of vitiligo consist of topical and/or systematic agents, and ultraviolet therapy. In patients with stable vitiligo, the lack of reliably effective medical therapies has led to the development of surgical treatment options. The disease develops gradually or rapidly in a few months and then stops. 12 In many countries, the recording of patient-defined therapy goals and patient satisfaction with treatment has already been an important component in the assessment of drugs and medicinal products. 13 Allocation decisions and cost reimbursement are mostly based on the therapeutic benefit from the patient s perspective The objective of current study was to describe characteristics of vitiligo and record clinical spectrum of vitiligo patients, using a predesigned questionnaire. Our study was beneficial for comprehensive understanding of vitiligo. METHODS Patients Our study was approved by the human research committee of each medical university, and it was conducted in accordance with the guidelines of the Declaration of Helsinki. Vitiligo patients or guardians who presented to the clinic were invited Correspondence: Bihuan Xiao, M.D., Department of Dermatology, No. 1 Hospital of China Medical University, Heping District of Nanjing North Street No. 1, Shenyang 111, China. y31@sina.com Received March 17; accepted 19 July Japanese Dermatological Association 39

2 Z. Lin et al. to participate in an exploratory questionnaire and signed informed consent. The investigation was conducted in three hospitals which were located in each provincial capital (Shenyang, Changchun, Harbin) of northeast China. The investigation was conducted from November 1 to November 16. If the patient was non-educated, unable to read or unable to fill in the questionnaire, the investigator would read for him/her all the questions and fill in the questionnaire instead of them. Contents of questionnaire The questionnaire was made up of two sections related to vitiligo as much as possible. The first section covered the sociodemographic information (three items), including sex, age and origins of patients. The second section involved the aspects of clinical information (24 items): 1. History of vitiligo (six items): age that the patients presented signs of vitiligo for the first time, the sites that vitiligo signs appeared for the first time, the causes of vitiligo, whether the vitiligo was active lately, how the vitiligo progressed earlier, whether the skin was itchy or red before the white patch appeared. 2. Vitiligo description (three items): normal skin color, type of vitiligo, affected body surface area (BSA, one palm area was equivalent to ~1% of one s total BSA). 3. Vitiligo treatments to date (six items): types of treatments received, what was the stage of vitiligo (active or stable) at the time of the latest treatment, the result of the latest treatment, the duration of the latest treatment, how the patients follow the treatment protocol, whether the disease recurs or starts spreading again after the treatment. 4. Skin condition (four items): presence of gray hair, family history of early hair graying, prone to sunburn or not, presence of halo nevus or not.. Other conditions (five items): presence of allergies, chronic diseases other than vitiligo, melanoma or other skin cancers, and close blood relatives who suffer from vitiligo, and the approximate cost of vitiligo treatment and/or camouflage to date. Statistical method Statistical analysis was performed using SPSS version 22. software (SPSS, Chicago, IL, USA). Comparisons were performed using the v 2 -test. A P-value was considered statistically significant when it was less than.. RESULTS Sociodemographic data A total of 983 vitiligo patients answered the questionnaire,.9% of whom were female and 49.1% male. The mean age of all patients was years ( ), ranging from 4 months to 79 years. Respectively, the ages of women and men were 31 years ( ) and 28 years ( ). The proportion of patients stratified by sex and age is shown in Table 1. The origins of all patients were 413 (42.%) from Liaoning Province, 41 (42.2%) from Jilin Province and 1 (1.8%) from Heilongjiang Province. Clinical information History of vitiligo (six items) 1. The ages that patients first noticed signs of vitiligo varied in different age groups. Of all patients, 19 years was the most common affected group (26%), second to years (%), and more than 6 years was the least affected group (1%) (Fig. 1). 2. The sites where vitiligo first appeared included head/neck/- face, lips, hand/foot, elbow/knee, groin, genitals, trunk, armpit, arm/leg (excluding hands, elbows, feet, knees), mucous membrane (e.g. inside mouth, nose) or other. Most patients (94.1%) were affected at one body site, and.9% were affected at more than two sites (Table 2). 3. The causes of vitiligo included emotional distress, physical skin damage, pregnancy or childbirth, medication sideeffect, cosmetic or hair product, deodorant or perfume, sunburn or prolonged sun exposure, exposure to rubber product or hazardous materials, vaccination, other, or not sure. Most patients (88.%) chose one cause, and 8.1% chose two or three causes. More than % of patients thought that emotional distress was one of the factors leading to their vitiligo (Table 2). 4. Considering whether the vitiligo had been active lately, 46.3% of patients felt that their disease had actively spread in the last month or two, and the other 3.7% of patients felt that their disease had been stable for more than 3 months.. With regard to the question about how vitiligo had progressed earlier, 8.3% of patients selected a quick, short burst, then limited spreading; in contrast, the other 41.7% chose slow, progressive spreading for several years. 6. Before the white patch appeared, most patients (83.7%) had not had any symptoms on the affected skin and 16.3% of patients reported skin itching or redness. Vitiligo description (three items) 1. The normal skin color of patients was described as pale white, fair, darker white, light brown, brown, dark brown or black (Fig. 2). Table 1. Number and proportion of enrolled patients stratified by sex and age Age (years) Female (%) Male (%) <1 49 (.) 7 (.8) (6.7) 84 (8.) (13.4) 18 (16.1) (1.9) 74 (7.) (7.3) (.1) 9 4 (4.6) 28 (2.8) >9 (3.) 32 (3.3) Total (.9) 483 (49.1) 4 17 Japanese Dermatological Association

3 Survey of vitiligo in China >6 Age group (years) Figure 1. Ages that signs of vitiligo were first noticed in different age groups Pale white fair Darker white Light brown The normal skin color Brown Dark brown/black Table 2. Distribution of vitiligo signs and causes First site of appearance of vitiligo No. of sites Head/neck/face 277 Lip 126 Hand/foot 187 Elbow/knee 1 Groin 79 Genital 49 Trunk 173 Armpit 26 Arm/leg (excluding hand, elbow, foot, knee) 7 Mucous membrane (e.g. inside mouth, nose) Other (anus, eyebrow, hair, eyelash) 1 Causes of vitiligo No. of patients Emotional distress 2 Physical skin damage 283 Pregnancy or childbirth 23 Medication side-effect Cosmetic or hair product 8 Deodorant or perfume 1 Sunburn or prolonged sun exposure 29 Rubber product Exposure to hazardous materials 6 Vaccination 1 Not sure The types of vitiligo were described as generalized (vulgaris, acrofacial, universal), localized (mucosal, focal, segmental) or mixed (combined segmental, acrofacial and/or generalized) (Fig. 3). 3. Most patients (3%) reported that the BSA of vitiligo patches was 1% or less and the least patients (2%) reported 7 1% (Fig. 4). Figure 2. Distribution of normal skin color of enrolled patients Vulgaris Actificial Universal Mucosal Type of vitiligo Focal Segmental Mixed form Figure 3. Distribution of patients with various vitiligo types < % BSA (body surface area) Figure 4. Distribution of patients with various body surface areas of vitiligo patches. Vitiligo treatments to date (six items) 1. More than half of the patients (64.6%) chose at least two types of treatments. Approximately 1.2% of patients could not remember their previous treatments and 13.6% of patients could not remember their latest treatments. 17 Japanese Dermatological Association Approximately 6.7% of patients had seen the doctors for the first time or had just been diagnosed with vitiligo and had not received any therapy to date (Table 3). 2. At the time of the latest treatment, 41.6% of patients were at the stage of active vitiligo (spreading in the last month or 41

4 Z. Lin et al. Table 3. Types of treatments received and the results of the latest treatment (n [%]) Treatments type Previous Latest Light, laser or phototherapy Systemic (pills, injections) Topical (creams) Surgical 4 2 Psychological counseling 1 2 Traditional (indigenous or 7 1 folk) medicine Complementary (i.e. vitamins, food supplements) 13 8 Results of the latest treatments Stable Active Total Poor response Continued or new white (18.7) patches appeared Continued but slowed (24.9) significantly Good response Completely stopped but (41.1) patches still remain Almost or completely (1.3) disappeared Total (%) 74 (8.4) 49 (41.6) 983 two) and 8.4% were at the stage of stable vitiligo (no progression over the last 3 months before treatment). 3. As a result of the latest treatment, almost 43.6% of patients achieved good response (completely stopped or almost disappeared) (Table 3). More patients at active stage showed good response compared with the patients at stable stage (v 2 = 7.866, P <.). 4. The duration of the latest treatment ranged. 36 months, and 86.8% of patients had been treated for a period of shorter than 6 months.. The majority of patients (76.%) followed the treatment protocol rigorously (maybe skipped one or two only),.% of patients followed somewhat closely (maybe skipped a few or more) and 4.% of patients followed loosely or had to stop early. 6. After treatment, 8.7% of patients reported that the disease did not recur or start spreading again. New lesions were found after 1 month in 3.1% of patients, after 1 year in 2.8% of patients or after 1 years or more in.4% of patients. Skin condition (four items) 1. Most patients (69.2%) had no or little gray hair and 22.9% had moderate gray hair. Only 6.3% of patients had a lot of gray hair and 1.6% of patients had all gray hair. 2. Family history of early hair graying comprised 1.4% of patients. 3. Seventeen percent of patients sunburned easily. 4. Presence of halo nevus of the skin was recorded in 6.8% of patients (defined as a benign mole on the skin with a white ring or halo around it). Other conditions (five items) 1. The allergies included substances the patients had touched, insect stings, airborne allergens, sun reactions, food, allergens or intolerance and medications, and 27.8% of patients reported that they had allergies (Table 4). 2. Other than vitiligo, chronic diseases were reported by 89 patients. The diseases included psoriasis, rheumatoid arthritis, diabetes, thyroid, eczema, urticaria, hypertension and ankylosing spondylitis (Table 4). Chronic diseases were present in 12.6% (8/462) of patients with a BSA of more than 1%, and more than 6% (31/49) in patients with a BSA of 1% or less (v 2 = , P <.). 3. One patient had melanoma. 4. The minority of patients (11.3%) had close blood relatives who suffered from vitiligo. The blood relatives were brothers, sisters, fathers, father s brother, mother s brother, father s sister and mother s sister (Table 4).. Almost 4% of patients spent yuan (~$US43.4) to 6 yuan (~$US868.8), 6.7% of patients spent nothing Table 4. Allergies, chronic diseases other than vitiligo, close blood relatives who suffered from vitiligo (n [%]) Types of allergies Substances you touch 39 Insect stings 26 Airborne allergens 2 Sun reactions 42 Food allergens or intolerance 62 Medications 6 Other 37 None 669 Chronic diseases BSA 1% BSA >1% Psoriasis 4 21 Diabetes 6 7 Rheumatoid arthritis 2 11 Thyroid 2 7 Ankylosing spondylitis 1 Eczema 9 Urticaria 2 Hypertension 3 4 Total 31 (6.) 8 (12.6) Close blood relatives who suffered from vitiligo Brother 16 (14.4) Sister 13 (11.7) Father (27.) Mother 17 (1.3) Father s brother 1 (9.1) Mother s brother 8 (7.2) Father s sister 9 (8.1) Mother s sister 8 (7.2) Japanese Dermatological Association

5 Survey of vitiligo in China Nothing < RMB and 2.% of patients were not sure about how much they spent (Fig. ). DISCUSSION 1 RMB 1 6 RMB 61 6 RMB RMB exchange rate 1 USD = 6.9 RMB 61 1 RMB 1 RMB Not sure Figure. Approximate costs of vitiligo treatment and/or camouflage to date. Sociodemographic data Our investigation showed nearly equal numbers of female and male vitiligo patients, indicating no sex difference of vitiligo prevalence. Our result was in accordance with previous publications, 1,17,18 although sporadic studies showed a preponderance of women. 19 Besides, the investigated patients, either female or male, were mostly young and middle-aged. History of vitiligo Previous studies showed that the peak onset of vitiligo was 1 years. 18, In our study, 19 years was the most common peak onset age, secondary to and 6 12 years. Our result refined the onset age group. The distribution of vitiligo onset is asymmetrical, but it shows that most patients suffer from the disease in childhood or young adulthood. The head/face/neck was the most commonly involved site in our study, followed by hand/foot, which was consistent with the study of Hadler et al. 21 The results support the theory that sun exposure or physical trauma are possible triggering factors of vitiligo. Previous studies reported that emotional disturbance or stress and physical trauma were the two most common precipitating factors that may contribute to the disease onset. 22,23 In our study, approximately half of patients selected emotional distress as one of the factors leading to their vitiligo, and 11.4% of patients reported physical skin damage as a susceptible factor. Unfortunately, 38.4% of patients could not determine the cause of their vitiligo. Identifying risk factors and educating patients on how to avoid these risk factors are important in preventing disease progression. Prevention through the early detection of risk factors is considered more important than treatment itself. 17 Japanese Dermatological Association Vitiligo often tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. In this study, patients with spreading and newly formed vitiligo patches in the previous 3 months were considered to be at the active stage and 3.7% of patients were at this stage. The patients at active stage, especially of quick style, usually have a strong will to see doctors because of fearing of the disease. Generally, vitiligo is considered to have no symptoms on the local skin. It is an important differential point to other hypo- or depigmentary diseases. In our study, however, pruritus and photosensitivity were found in 16.3% of patients. Another study found that vitiligo was associated with pruritus in % of patients. 24 The finding collides with common sense and gives dermatologists new information on vitiligo. Vitiligo description The normal color of nearly % of our investigated patients was light brown. Pale white, fair or dark white occupied 1 16%, respectively. These manifestations accord with the characteristics of the Chinese Han population. In our study, most patients had the generalized form. Among these patients, vitiligo vulgaris was the most common type, which was in accordance with the investigation by Liu et al. 18 Over % of patients reported that the BSA of vitiligo patches was less than 1%, which was similar to the result of Serarslan et al. 2 Vitiligo treatments to date Because of the unpredictable therapeutic response of the disease, it is difficult to apply any general rules regarding the choice of therapy. According to a report in Japan, topical steroids, vitamin D 3 analogs and tacrolimus have been applied in almost all hospitals (~9%) and approximately 7% of institutes. Phototherapies are prevalent and are an evidencebased, highly effective treatment. 26 In our study, more than half of the patients chose at least two types of treatments. Systemic drugs, topical agents or light therapies were the popular treatments. However, as we have mentioned above, emotional distress is the common risk factor of incidence and aggravation of vitiligo. Only three patients sought psychological counseling. Education should be emphasized in this aspect. By the latest treatment, most patients did not achieve the most desirable results, although a majority of patients followed the treatment protocol rigorously. In addition, most patients were at stable stage before they accepted the latest treatment and reported that the disease did not recur (2.6%) or start spreading again after treatment (47.4%). However, the vitiligo at stable stage has poorer response than that at active stage. We assume that stable stage vitiligo is more difficult to treat than active stage vitiligo. Besides, the fact that most patients accepted the latest treatment under a period of less than 6 months may interpret the undesirable efficacies. The treatment duration may be not long enough for the stabilization or recovery from the disease. Skin condition Gray hair, a family history of early hair graying, susceptibility to sunburn and halo nevus are signs of inherited traits of some 43

6 Z. Lin et al. vitiligo patients, although they were not usual in vitiligo patients. The patients who have these skin conditions should especially pay attention to the early diagnosis of vitiligo of their next generation. In 12, a survey was conducted to assess hair color and graying in a large worldwide sample of human subjects, according to ethnic/geographic origin and natural hair color. 27 The percentage of people at around the age of years who had at least % gray hair was 6 23%, well below that expressed by the rule of thumb in the Japanese population. 28 In our survey of vitiligo patients, 22.9% had moderate, 6.3% had a lot and 1.6% had all gray hair. Ordinary hair graying is commonly considered as a sign of aging and most people with gray hair do not have vitiligo of the skin. However, vitiligo patients as well as their relatives frequently have prematurely gray hair and this can be considered as a manifestation of the vitiliginous process. More than 2% of patients reported that they had allergies, and 9% of patients had chronic diseases other than vitiligo. The discovery of a T cell infiltrating in the margin of inflammatory vitiligo was the first clue to the role of cellular immunity in the pathogenesis of vitiligo. At present, the evidence has shown that vitiligo is closely related to genetics and immune responses, and approximately % of vitiligo patients manifest concomitant occurrence of other autoimmune diseases. 1 In our study, 12.6% of patients with large white patches (>1% BSA) had chronic diseases, twice that of the patients with small white patches ( 1% BSA). We assume that vitiligo patients with BSA of 1% or less have many less comorbidities of chronic/autoimmune diseases than patients with large BSA involvement. It also indicates that it is unnecessary to perform the related screenings in all vitiligo patients because of additional economic burden. None of our patients reported pernicious anemia, which should be especially investigated in future studies. Other conditions In our study, a positive family history was present in 11.3% of the patients. The rate was close to another study from Turkey. 29 Other documents from Hann and Akrem were 13% and 17.8%, respectively. These results support the hypothesis that vitiligo has a polygenic or autosomal dominant inheritance pattern with incomplete penetrance and variable expression. For a majority of patients, the total costs in dealing with vitiligo ranged from yuan (~$US43.4 USD) to 6 yuan (~$US868.8). We were not sure whether these costs were compensated by insurance or not. According to previous reports, patients who were willing to pay a lot experienced a greater loss in quality of life. These costs may cover treatments of disease, sunscreen products, camouflage and other related expenses. Because no treatment can cure vitiligo to date, the disease has a long duration. The costs are suspected to be much more than we surveyed and the burdens of the vitiligo patients were very heavy indeed. In conclusion, until now there has been a lack of information about the epidemiological and clinical profile of vitiligo in the northeast of China. The current study gives a comprehensive understanding of vitiligo by collection of sociodemographic data and clinical information. The two most important findings are that active vitiligo responds more readily to the treatments than stable vitiligo and complications with other autoimmune type of diseases are more frequently observed in severe vitiligo patients than mild patients. The results of the present study will help us facilitate collaboration between scientists, predict the prognosis of vitiligo and ultimately develop new therapies to some extent. ACKNOWLEDGMENT: This work was supported by the Vitiligo Research Foundation (VRF1111/1). CONFLICT OF INTEREST: None declared. 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