Development of evidence-based consensus on critical issues in the management of patients with vitiligo: A modified Delphi study.

BACKGROUND/PURPOSE: Vitiligo remains a major challenge in dermatology. However, much of the treatment remains unclear, because little evidence is available. We sought to answer some critical questions pertaining to management of vitiligo patients. METHODS: A modified Delphi process among 31 vitiligo experts was conducted. A total of 12 clinical vitiligo treatment questions without clear answers were collected via a vote. To address each question, two members performed systematic literature reviews and prepared draft statements along with the levels of evidence and strength of recommendation. After reviewing the draft, all expressed their extent of agreement from 1 (strong disagreement) to 9 (strong agreement) for each item. The drafts were revised to reflect suggested comments. Discussion continued until all members agreed with the ultimate decision. RESULTS: The consensus process was completed after five rounds. We identified the best answers to 12 key questions, including issues on long-term phototherapy, systemic and topical corticosteroids, topical calcineurin inhibitors, immunosuppressants, excimer laser treatment, and surgical interventions. CONCLUSION: This consensus would complement current guidelines and aid both physician and patient decision-making in the treatment of vitiligo.

Combination treatment with excimer laser and narrowband UVB light in vitiligo patients.

BACKGROUND: For the treatment of vitiligo, narrowband UVB (NBUVB) light is considered the most effective for nonsegmental vitiligo, while excimer laser treatment is commonly used for localized vitiligo. However, treatment areas may potentially be missed with excimer laser treatment. OBJECTIVE: We aimed to evaluate the effect of combinational treatment with NBUVB light and excimer laser on vitiligo. METHODS: All patients were first treated with NBUVB; excimer laser was then applied in conjunction with NBUVB phototherapy due to a slow response or no further improvement with continuous NBUVB treatment alone. To minimize adverse effects, a fixed dose of NBUVB was administered, and the dose of excimer laser was increased based on patient response. RESULTS: Among 80 patients, 54 patients showed responses after combination with excimer laser; however, 26 patients (32.5%) showed no remarkable change after combination therapy. Of the 26 patients who showed no further response, 12 patients (46.1%) presented with vitiligo on the acral areas, which are known to the least responsive sites. CONCLUSION: Our study suggests that combined treatment of NBUVB and excimer laser in vitiligo may enhance the treatment response without remarkable side effects, therefore might also increase the compliance of the patients to the treatment.

siRNA-mediated knock-down of COX-2 in melanocytes suppresses melanogenesis.

Cyclooxygenase-2 (COX-2) is an enzyme induced in response to multiple mitogenic and inflammatory stimuli, including UV light. UV-induced COX-2 expression induces production of prostaglandin E2 (PGE2) in keratinocytes, which mediates inflammation and cell proliferation. Until recently, studies regarding COX-2 and PGE2 in the skin have focused on keratinocytes and skin cancer and the effect of PGs produced by keratinocytes on melanocytes. However, the effects of COX-2 itself or COX-2 inhibitors on melanogenesis are not well known. Therefore, to establish the role of COX-2 in melanogenesis, we investigated the effects of knock-down of COX-2 in melanocytes on melanin production and the expression of melanogenic molecules through silencing of COX-2 expression with COX-2 short interfering RNA (siRNA). COX-2 knock-down in melanocytes decreased the expressions of tyrosinase, TRP-1, TRP-2, gp100 and MITF and also reduced tyrosinase enzyme activity. Furthermore, COX-2 siRNA-transfected melanocytes showed markedly reduced alpha-melanocyte stimulating hormone (α-MSH)-induced melanin production. In addition, α-MSH-induced COX-2 expression in both scrambled siRNA-transfected and COX-2 siRNA-transfected melanocytes was greater than α-MSH-untreated cells. Our results suggest that COX-2 might be a candidate target for the development of anti-melanogenic agents and α-MSH-induced pigmentation could be closely associated with COX-2 expression. COX-2 inhibitors might therefore be of particular use in whitening cosmetics for hyperpigmentation disorders such as melasma, postinflammatory hyperpigmentation and solar lentigo.

The effect of 308nm excimer laser on segmental vitiligo: a retrospective study of 80 patients with segmental vitiligo.

BACKGROUND: Segmental vitiligo (SV), which frequently accompanies poliosis, indicating a poor prognosis that is likely resistant to treatments. OBJECTIVES: In this study, we performed a retrospective analysis to evaluate the treatment response to 308 nm excimer laser in SV patients. METHODS: A retrospective chart and photographic review was performed on 80 SV patients who had been treated with 308nm excimer laser for >3 months. RESULTS: Eighty patients with SV (mean age: 24.0 years ± 15.3, males: 50%) were included in this study. The mean grade of repigmentation was 2.3 after 20.6 months of mean treatment duration; 23.8% of 80 patients showed grade 4, 20% showed grade 3, and 56.2% showed grade 1-2 repigmentation. However, none of them achieved complete repigmentation with excimer laser. The degree of repigmentation was positively correlated with treatment duration (r=0.315, P=0.004) and cumulative ultraviolet (UV) dosage (r=0.366, P=0.001), whereas it was negatively correlated with disease duration (r=-0.265, P=0.017). CONCLUSION: This study suggests that SV has a better repigmentation response when excimer laser is used at earlier stages of the disease and long-term use and high cumulative UV energy of the excimer laser elicit better responses. Additional treatments like surgical procedures in addition to excimer laser should be considered for complete repigmentation.

Xanthelasma palpebrarum treatment with a 1,450-nm-diode laser.

BACKGROUND: Various treatments of xanthelasma palpebrarum have been studied, including surgical excision, treatment with chemicals, and ablative laser therapy, but these methods have some disadvantages. Recently, nonablative laser therapy has been proposed as a treatment for xanthelasma palpebrarum. OBJECTIVE: To investigate the efficacy and safety of a 1,450-nm-diode laser in the treatment of xanthelasma. MATERIALS AND METHODS: Sixteen patients were treated using a 1,450-nm-diode laser. Fluences of 12 J/cm(2) , a 6-mm spot size, and a dynamic cooling device setting of 20 to 30 ms were used. One to four treatments 4 to 6 weeks apart were given to each patient. Photographs were taken before each treatment session and 4 to 6 weeks after the last treatment. RESULTS: Two (12.5%), eight (50%), and four (25%) of the 16 patients were scored as having some (20-40% clearing), moderate (40-60% clearing), and marked (60-80% clearing) improvement, respectively. Focal mild transient hyperpigmentation was noted in five patients. Post-treatment local swelling lasted 3 to 4 days. CONCLUSION: The 1,450-nm-diode laser treatment is a new, valuable treatment option for xanthelasma palpebrarum, offering relatively mild side effects. Studies including long term follow up and a comparison with alternative treatment modalities are necessary to further assess the clinical utility of this treatment. The authors have indicated no significant interest with commercial supporters.

Classification of facial vitiligo: A cluster analysis of 473 patients.

Vitiligo has a substantial negative impact on quality of life in affected patients, especially those with the involvement of the face. However, the current system can barely distinguish between specific patterns of facial involvement except for the segmental type when focusing only on facial lesions. We classified facial vitiligo into three distinct subtypes using cluster analysis based on facial topography (n = 473): centrofacial vitiligo (72.9%), panfacial vitiligo (18.0%), and hairline vitiligo (9.1%). Centrofacial vitiligo was the most common type and is thought to comprise the typical facial involvement of generalized vitiligo. Panfacial vitiligo was a distinct subtype with onset in old age and less involvement of other body parts. Hairline vitiligo was another distinct subtype with onset in old age and a poor response to conventional phototherapy. A relevant classification system could help us to explore the causes, anticipate the prognosis, and manage the condition in patients with vitiligo.

Pigmentary disorders in the South East.

In this article, new information is introduced regarding vitiligo and melasma based on clinical studies of Korean patients and specific pigmentary disorders that occur in Asians. These disorders can be psychologically distressing because of their visible nature. They are especially resistant to various kinds of conventional treatments and tend to have a chronic progression that makes patients doubt the results and the prognosis.

Human papillomavirus type 59 identified in a verrucous cyst of the flank.

The verrucous cyst is a non-plantar epidermoid cyst with histopathological features of human papillomavirus (HPV) infection, including papillomatosis and hypergranulosis of the cyst lining. We report the first case of a verrucous cyst demonstrating not only the histopathological and immunohistochemical features of HPV infection, but also homology with HPV type 59 on HPV genotyping. A 28-year-old male developed a palpable mass in his right flank. Histological examination revealed an intradermal cyst lined by an acanthotic and papillomatous squamous epithelium with prominent keratohyaline granules and squamous eddies. The keratinocyte nuclei were positive for papillomavirus antigens on immunohistochemistry and HPV genotyping demonstrated a homology to HPV type 59, a high-risk genital type. Although we only experienced a single case with such a finding, we suggest that it may be necessary to subject patients with verrucous cysts to a closer follow up for better characterization of their clinical behavior.

Prevalence of vitiligo and associated comorbidities in Korea.

PURPOSE: Vitiligo prevalence and its associated comorbidities rate have been reported variably among different populations. We aimed to determine the prevalence of vitiligo in Korea along with the baseline rate of comorbidities and compared the risks to the general population using hospital visit information of the total population in Korea. MATERIALS AND METHODS: We assessed demographic characteristics of vitiligo patients in Korean population from 2009 to 2011 in a nationwide data from Health Insurance Review Assessment Service. Patients who had at least one visit to Korea's primary, secondary, or tertiary referral hospitals with International Classification of Diseases, 10th Revision, Clinical Modification diagnosis code for vitiligo were identified. As a supplementary study, comorbidities associated with vitiligo were selected for further review to calculate relative risks compared to the general population. RESULTS: The annual prevalence of vitiligo determined by hospital-visiting rate in Korea was 0.12% to 0.13% over a three year period. In sync with other previous epidemiological studies, there was bimodal distribution among the age groups and no difference between genders. Also, vitiligo in Korean population was associated with various autoimmune/non-autoimmune diseases such as thyroiditis, atopic dermatitis, and psoriasis. CONCLUSION: This study was by far the most comprehensive review on prevalence of vitiligo using a data of total population in Korea. The prevalence is within a range of those reported in previous literatures, and increased risk of comorbidities such as thyroid diseases and psoriasis in vitiligo might aid clinicians in the initial work up of vitiligo patients and concurrent follow ups.

Concomitant use of an infrared fractional laser with low-dose isotretinoin for the treatment of acne and acne scars.

BACKGROUND: Acne scarring has lifelong sequelae. Fractional photothermolysis (FP) has been shown to provide fast recovery from acne within a short period, thereby aiding skin rejuvenation. Isotretinoin is a well-known, effective drug for the treatment of severe recalcitrant acne. This study investigated the safety and the efficacy of infrared fractional laser treatment in conjunction with low-dose isotretinoin for the treatment of acne and acne scars. MATERIALS: A 1550 nm Erbium-doped fiber laser was used to treat 35 patients with acne scarring. All the patients had taken isotretinoin (10 mg/day) for more than one month prior to the commencement of the fractional laser treatment. RESULTS: There was no aggravation of acne scars, hypertrophic scars, or keloids. Most of the patients (33 patients) received reduced microthermal damage zone (MTZ) treatment. Eighty percent of the treated patients (28 patients) demonstrated more than a fair improvement. The total average score on the global acne scarring classification before treatment was 13.5, and the score after treatment was 11.2. CONCLUSION: Acne and acne scars can be treated more effectively by concomitant use of an infrared fractional laser with low-dose isotretinoin with reduced MTZ densities. Most patients showed more than a fair improvement, and there was no aggravation of the scars.

A Multicenter Collaborative Study by the Korean Society of Vitiligo about Patients' Occupations and the Provoking Factors of Vitiligo.

BACKGROUND: It was previously thought that persons with genetic predispositions to vitiligo develop the condition after exposure to various precipitating environmental factors. However, in many cases, the aggravating factors of vitiligo have not been clearly identified. OBJECTIVE: To identify the aggravating factors of vitiligo in the working environment and daily life. METHODS: A total of 489 vitiligo patients were recruited from 10 institutions in South Korea; patients were provided with a questionnaire about environmental factors and behavior patterns in the workplace and in daily life, and their association with vitiligo. RESULTS: Ninety-five of the 470 enrolled patients (20.2%) answered that environmental risk factors in daily life and in the workplace affected the development of vitiligo. The most frequently attributed causes were trauma and burn (13.6%), followed by sunlight (12.8%), stress (12.8%), cleaning products/disinfectant/chemicals (4.9%), and hair dye (2.1%). CONCLUSION: Vitiligo of the hand and foot was associated with frequent exposure to aggravating materials and overexposure to sunlight, along with frequent trauma of these areas, all of which could be considered important risk factors of vitiligo. The development of vitiligo could potentially be controlled through the early detection of aggravating factors.

Comparison of the psychological impacts of asymptomatic and symptomatic cutaneous diseases: vitiligo and atopic dermatitis.

BACKGROUND: Vitiligo and atopic dermatitis (AD) are common dermatological disorders which may cause significant psychological and social distress leading to impaired quality of life (QoL) in patients. OBJECTIVE: We evaluated the degree of psychological stress and impairment of QoL in vitiligo patients as compared with AD patients and normal controls (NCs). METHODS: A total of 60 patients from each group and 60 NCs were enrolled. Five questionnaires on depression (Beck depression inventory, BDI), state anxiety (SA) and trait anxiety (TA), interaction anxiousness (IAS), private body consciousness (PBC) and dermatologic QoL were used. RESULTS: The vitiligo patients had a significantly higher level of TA (p<0.01), PBC (p<0.001) and impaired QoL (p<0.001) than NCs, but not BDI, SA and IAS. The AD patients had significantly higher scores for all five questionnaire items compared with NCs. In the comparison between the AD and vitiligo groups, all of the indexes except body consciousness were higher in AD patients than in vitiligo patients: BDI (p<0.01), SA (p<0.05), TA (p<0.001), IAS (p<0.01) and impaired QoL (p<0.001). Exposure of vitiligo lesions was not a significant variable in the analysis of the contribution of clinical variables of vitiligo on psychological stress and QoL. CONCLUSION: Vitiligo, which is not accompanied by any symptoms, involves less psychological impact than AD, which is accompanied by itching. Compared to NCs, however, the elevated general anxiety and body consciousness in patients with vitiligo suggests that they may be more concerned with the aggravation of hypopigmented patches than difficulties in social interactions.

Expression of cytosolic NADP(+)-dependent isocitrate dehydrogenase in melanocytes and its role as an antioxidant.

BACKGROUND: Cytosolic NADP(+)-dependent ICDH (IDPc) has an antioxidant effect as a supplier of NADPH to the cytosol, which is needed for the production of glutathione. OBJECTIVE: To evaluate the expression of IDPc in melanocytes and to elucidate its role as an antioxidant. METHODS: The knock-down of IDPc expression in immortalized mouse melanocyte cell lines (melan-a) was performed using the short interfering RNA (siRNA)-targeted gene silencing method. After confirming the silencing of IDPc expression with mRNA and protein levels, viability, apoptosis and necrosis, as well as ROS production in IDPc-silenced melanocytes were monitored under conditions of oxidative stress and non-stress. Also, the ratio of oxidized glutathione to total glutathione was examined, and whether the addition of glutathione recovered cell viability, decreased by oxidant stress, was checked. RESULTS: The expression of IDPc in both primary human melanocytes and melan-a cells was confirmed by Western blot and RT-PCR. The silencing of IDPc expression by transfecting IDPc siRNA in melan-a cells was observed by Western blotting and real-time RT-PCR. IDPc knock-down cells showed significantly decreased cell viability and an increased number of cells under apoptosis and necrosis. IDPc siRNA-treated melanocytes demonstrated a higher intensity of DCFDA after the addition of H(2)O(2) compared with scrambled siRNA-treated melanocytes, and a lower ratio of reduced glutathione to oxidized glutathione were observed in IDPc siRNA transfected melanocytes. In addition, the addition of glutathione recovered cell viability, which was previously decreased after incubation with H(2)O(2). CONCLUSIONS: This study suggests that decreased IDPc expression renders melanocytes more vulnerable to oxidative stress, and IDPc plays an important antioxidant function in melanocytes.

Quality of life for Korean patients with vitiligo: Skindex-29 and its correlation with clinical profiles.

Vitiligo considerably influences the psychological well-being of patients. Disease-induced disfigurement can cause patients to experience a high level of stigmatization, which can lead to psychosocial stresses and negative impacts on quality of life (QOL). This study aims to ascertain the QOL of vitiligo patients compared to patients with other mild skin disorders. We also attempt to study which clinical features of vitiligo are closely related to the patient's QOL. One hundred and thirty-three vitiligo patients and 112 patients with mild skin disorders were analyzed. All participants were asked to fill out questionnaires covering comprehensive clinical profiles and the Korean version of Skindex-29. Statistical correlation between Skindex-29 and each clinical profile were analyzed. The symptom scale of Skindex-29 was significantly lower in vitiligo patients than in controls, but the function scale and the emotion scale were significantly higher in the vitiligo group than in controls. However, the difference in function scales between groups was significant in female patients, but not in male patients. Several clinical profiles, such as duration of disease, severity scores and previous history of treatments, showed close correlations with the function scale. Family history of vitiligo, Köebner phenomenon, patients' perspectives on disease prognosis, and discordance of the severity scores between physicians and patients also influenced the Skindex-29 subscales differently. In conclusion, the present study suggests that patients with vitiligo were highly affected in the functional and emotional aspects of QOL, with some sex differences. Various clinical features may play an important role in the QOL of vitiligo patients.