Comparison of efficacy and safety profile of topical calcipotriol ointment in combination with NB-UVB vs. NB-UVB alone in the treatment of vitiligo: a 24-week prospective right-left comparative clinical trial.

BACKGROUND: Narrow-band ultraviolet B (NB-UVB) is an effective and safe treatment for vitiligo. Calcipotriol, a synthetic analogue of 1,25 dihydroxyvitamin D3 may regulate melanin synthesis. Several clinical studies have been conducted but the synergistic effect of addition of calcipotriol to NB-UVB in the treatment of vitiligo is still debatable. OBJECTIVES: To compare the efficacy and safety of topical calcipotriol (0.005%) in combination with NB-UVB vs. NB-UVB alone in generalized vitiligo. METHODS: A prospective right-left comparative study including 27 patients of vitiligo was conducted for 24 weeks. On one side, calcipotriol was applied twice a day. NB-UVB was administered thrice a week. Response to treatment was assessed using change in Lund and Browder (L&B) score for percentage reduction in body surface area, investigator's global assessment (IGA) and patient's global assessment (PGA) scores. Treatment related side effects were noted. RESULTS: Mean percentage reduction in L&B score at 24 weeks was 51.4% on NB-UVB and 49% on NB-UVB plus calcipotriol side (P = 0.557), mean IGA score on NB-UVB was 2.7 ± 0.5 and on NB-UVB plus calcipotriol was 2.6 ± 0.4 (P = 0.821) and mean PGA score on NB-UVB side was 5.6 ± 3.4 and on NB-UVB plus calcipotriol side was 5.8 ± 3.2 (P = 0.706). Perifollicular repigmentation that matched with the surrounding normal skin colour was seen in majority of patients on both treatment sides. Calcipotriol produced mild local adverse effects. CONCLUSIONS: Addition of calcipotriol to NB-UVB probably does not enhance the efficacy of treatment including extent of repigmentation and time to initial repigmentation. Larger, randomized placebo-controlled trials are required to determine whether addition of calcipotriol has any utility when administered with NB-UVB in the treatment of vitiligo.

Clinical and treatment characteristics determining therapeutic outcome in patients undergoing autologous non-cultured outer root sheath hair follicle cell suspension for treatment of stable vitiligo.

BACKGROUND: Autologous non-cultured outer root sheath hair follicle cell suspension (NCORSHFS) is a recently described novel cellular graft technique for the treatment of stable vitiligo. There is lack of data about various factors determining the repigmentation rate in vitiligo patients undergoing this novel surgical therapy. OBJECTIVE: To study the clinical characteristics and treatment variables determining therapeutic outcome in patients of stable vitiligo undergoing NCORSHFS. METHODS: Non-cultured outer root sheath hair follicle cell suspension was prepared from anagen hairs extracted from the occipital area. The number of melanocytes and hair follicle stem cells (HFSC) in the suspension was quantified by staining with anti-HMB45 and anti-CD200 antibody, respectively. In all patients, a 2 mm punch skin biopsy was taken from one of the vitiligo patch to be treated prior to surgery for assessment of histomorphological features. Post surgery patients were followed up at regular intervals for 24 weeks. RESULTS: Thirty patients (21 females, 9 males) with a clinical diagnosis of stable vitiligo, with a total of 60 target lesions were included in this study. The mean age of the study population was 21.10 ± 5.64 years. The number of melanocytes (P = 0.04) and HFSC (P = 0.01) transplanted were significantly higher among patients achieving optimum repigmentation (>75% repigmentation). There was a strong correlation between repigmentation at 24 week and number of melanocytes and HFSC transplanted. Number of HFSC transplanted and absence of dermal inflammation were significant predictors of achieving optimum repigmentation. CONCLUSION: The number of melanocytes and HFSC transplanted and absence of dermal inflammation were important determents of optimal repigmentation in patients undergoing NCORSHFS for treatment of stable vitiligo. Hence, refining the technique of NCORSHFS on the basis of these factors would help in achieving better surgical outcomes.

Type 2A Koebner phenomenon in vitiligo is distinct from other subtypes: observations from an Indian cohort.

BACKGROUND: Koebner phenomenon (KP) in vitiligo has been redefined and classified recently. OBJECTIVES: To study the clinical characteristics of various grades of KP. METHODS: In this prospective cross-sectional study, 202 patients with vitiligo were studied between January 2011 and December 2012 for the presence of KP. Based on the new Vitiligo European Task Force guidelines, KP was classified as type 1-3 and grades Ι-IV. Disease characteristics were studied in the various groups and subgroups based on the presence of KP. RESULTS: Koebner phenomenon was seen in 130 of 202 patients. The mean age of patients showing KP was 23.9 ± 13.6 years, compared with 19.3 ± 12.4 years for patients not showing KP (P = 0.02). The mean body surface area involved in the KP-positive group was 4.6 ± 5.6%, vs. 1.5 ± 1.1% in the KP-negative group (P = 0.001). Fifty-five patients experiencing KP received low-dose dexamethasone oral minipulse therapy compared with nine of those who did not (P = 0.01). Of the 130 patients with KP, grade Ι KP was seen in 32, grade II KP in 116, grade III KP in 22 and grade IV KP in 16. There was a significant difference between type 1 and type 2A KP, and between type 2A and type 2B KP. In contrast, type 1 and type 2B KP were found not to be significantly different and had a good degree of correlation. CONCLUSIONS: Patients with KP have a significantly higher age at onset, more extensive cutaneous involvement and are more likely to receive systemic steroids for disease control. Type 2A disease was found to be distinct from the other subtypes.

Spectrum of cutaneous manifestations of type 1 diabetes mellitus in 500 South Asian patients.

BACKGROUND: Data on cutaneous manifestations of type 1 diabetes mellitus (DM) is scarce. OBJECTIVES: To study the spectrum of dermatoses in patients with type 1 DM and the effects of disease duration and long-term glucose control on these cutaneous manifestations. SUBJECTS AND METHODS: After prior consent, clinical examination and relevant investigations were done in 500 subjects with type 1 DM enrolled between July 2011 and June 2012. Statistical tests were performed using SPSS 16. The presence of various dermatoses was correlated with the duration of diabetes. RESULTS: Of five hundred subjects, 339 (67·8%) had one or more dermatoses. The mean age of the patients was 16·9 ± 6·9 years (range 1-25 years) and mean total duration of diabetes was 4·43 ± 4·4 years. Cutaneous adverse effects related to insulin injections (CAII), comprising lipohypertrophy (41%), post-inflammatory hyperpigmentation (3%), lipoatrophy (0·6%) and acanthosis nigricans (0·4%), were the most common findings, followed by limited joint mobility (LJM) (16·8%), xerosis (15·8%) and scleroderma-like skin changes (10%). Patients having long-duration DM (> 4·4 years) were significantly more likely to have lipohypertrophy (P = 0·000), LJM (P = 0·000), scleroderma-like skin changes (P = 0·000), diabetic dermopathy (P = 0·000), acanthosis nigricans (P = 0·005) and skin tags (P = 0·002). Lipohypertrophy, LJM and scleroderma-like skin changes also showed significant correlation with blood glucose level. CONCLUSIONS: Our study suggests that cutaneous changes are common in young Asian patients with type 1 DM. Information, education and counselling of patients and care givers, and awareness among physicians is essential for the prevention and early management of these dermatoses.

Clinical and immunological outcomes of high- and low-dose rituximab treatments in patients with pemphigus: a randomized, comparative, observer-blinded study.

BACKGROUND: Rituximab is a promising therapy in pemphigus. However, there is no consensus on optimum dose. OBJECTIVES: To compare the efficacy, in terms of clinical and immunological outcomes in patients with pemphigus, of a high (2 × 1000 mg) vs. a low dose (2 × 500 mg) of rituximab. METHODS: This was a randomized, observer-blinded trial wherein 22 patients with pemphigus were randomized into two treatment groups. Patients received either two doses (day 0 and day 15) of 1000 mg rituximab or 500 mg rituximab, and were followed up for 48 weeks. Clinical activity was assessed by a blinded investigator. Indices of enzyme-linked immunosorbent assays (ELISAs) for desmoglein (Dsg)1 and Dsg3, and CD19 cell count were examined at regular intervals. RESULTS: There was no statistically significant difference in early and late clinical end points, and total cumulative dose of corticosteroids between the two groups. At week 40, the fall in Ikeda severity score was significantly more in the 2 × 1000 mg group than in 2 × 500 mg group (P = 0·049). Patients in the 2 × 500 mg group received a significantly higher cumulative dose of azathioprine (P = 0·018). The ELISA indices of Dsg1 and Dsg3 showed a statistically significant decline in the 2 × 1000 mg group only. B cell repopulation occurred earlier in the 2 × 500 mg group by 8 weeks. CONCLUSIONS: A few clinical and immunological study parameters have suggested improved outcomes in patients receiving high-dose (2 × 1000 mg) rituximab.

Modulation of LXR-α and the effector genes by Ascorbic acid and Statins in psoriatic keratinocytes.

Recent studies have revealed critical roles that nuclear receptors like LXR-α (Liver X Receptor- alpha) plays as a class of post-transcriptional gene regulator in skin development and diseases. Keeping in view the fact that LXR-α plays crucial role in keratinocyte proliferation and differentiation, it becomes imperative to dissect the pathways and role of LXR-α genomics in the pathogenesis of psoriasis with ultimate aim to explore novel preventive/therapeutic strategies as treatment options. To explore the effects of agonists and activators of LXR-α on its own gene expression and the putative targets in psoriatic keratinocytes. Identification of promoter sequences for (vitamin D receptor) VDR and Catalase were done using in silico analysis followed by ß-galactosidase (ß-gal) reporter plasmid assay in keratinocytes from clinically heathy subjects. Determination of relative levels of LXR-α,VDR and catalase in control versus treated cells upon activation of LXR-α with Atorvastatin + 22R hydroxycholestrol and Ascorbic acid + 22R hydroxycholestrol was done by PCR and Cell Proliferation Assay. The cells transfected with the reporter plasmid element for VDR and catalase showed more than 5 and 4 fold increase respectively in the ß-gal activity compared to the control. An increase of 55% in LXR-α gene expression at RNA level was observed in Atorvastatin + 22-R hydroxycholestrol compared to 24% in Ascorbic acid + 22-ROH cholesterol. The expression of the VDR and Catalase was significantly increased in both treated keratinocytes compared to its normal counterpart.

Comparison between autologous noncultured extracted hair follicle outer root sheath cell suspension and autologous noncultured epidermal cell suspension in the treatment of stable vitiligo: a randomized study.

BACKGROUND: Vitiligo is an acquired disorder of pigmentation caused by loss of epidermal melanocytes. Autologous noncultured epidermal cell suspension (NCES) and autologous noncultured extracted hair follicle outer root sheath cell suspension (NCORSHFS) are important surgical modalities for the treatment of stable vitiligo. OBJECTIVES: To compare NCES and NCORSHFS for producing repigmentation in stable vitiligo. METHODS: We randomized 30 patients with 47 stable vitiligo lesions into two groups. Patients in group 1 were treated with NCES, and those in group 2 with NCORSHFS. They were evaluated 16 weeks postsurgery for the extent of repigmentation, colour match, change in Dermatology Life Quality Index (DLQI) score and patient satisfaction. RESULTS: The extent of repigmentation was excellent (90-100% repigmentation) in 83% of lesions in the NCES group and 65% of lesions in the NCORSHFS group (P = 0·154). Repigmentation ≥ 75% (good repigmentation) was observed in 92% of lesions in the NCES group and 78% of lesions in the NCORSHFS group (P = 0·425). There was a significant improvement in DLQI score in both the groups, but the mean decrease among groups did not differ significantly (P = 0·244). However, patients in the NCES group were significantly more satisfied than the patients in the NCORSHFS group. No significant difference was seen in colour match and pattern of repigmentation. Adverse effects were minimal. CONCLUSIONS: Both NCES and NCORSHFS are safe and effective techniques with comparable efficacy. To the best of our knowledge, this is the first study directly comparing two different cellular techniques.

Scleromyxoedema with disseminated subcutaneous nodules: rare presentation of an uncommon dermatosis.

Scleromyxoedema, also known as generalized lichen myxoedematosus, is a cutaneous mucinosis characterized by a generalized papular and sclerodermoid eruption, mucin deposition, increased fibroblast proliferation and fibrosis. It is often associated with underlying monoclonal gammopathy, and it responds poorly to treatment. There are very few reports of nodular eruption in scleromyxoedema. We report a case of a prominent nodular eruption in an adolescent boy with scleromyxoedema without any underlying paraproteinaemia, and review the literature.

Methotrexate for treatment of lichen planus: old drug, new indication.

Treatment of generalized lichen planus is often disappointing and is associated with relapses. Though reports have suggested a beneficial role of various immunosuppressive and immunomodulatory agents, most of these reports are retrospective series or anecdotes. Oral methotrexate has been found to be useful in recent studies. In this study, we prospectively evaluated the role of low-dose oral methotrexate (15 mg/week in adults or 0.25 mg/kg/week for children) in generalized lichen planus. Mean improvement in 24 evaluated patients (two of them were of paediatric age group) at the end of 14 weeks of treatment was 79%. By the end of 24 weeks treatment, 14 of 24 (58%) patients had complete remission of their disease. Side effects were observed in 12 of 24 (50%) patients. Most of these adverse effects were mild; only one requiring treatment discontinuation due to significantly deranged liver function test. During post-treatment follow-up of 3 months, none had relapse of lichen planus. Overall, low- dose methotrexate is effective and reasonably safe option in treatment of eruptive lichen planus, provided haematological and biochemical parameters are regularly monitored.

Efficacy and safety of systemic methotrexate vs. acitretin in psoriasis patients with significant palmoplantar involvement: a prospective, randomized study.

BACKGROUND: Palmoplantar psoriasis (PP) is a chronic, inflammatory and proliferative dermatosis of the palms and/or soles with significant morbidity. It is notoriously difficult to treat and unresponsive to traditional topical agents. MATERIAL AND METHODS This was a prospective, randomized study involving 111 patients of psoriasis with significant palmoplantar disease. Patients meeting the eligibility criteria were randomly assigned to one of the two treatment groups. Patients in Group I received methotrexate in doses of 0.4 mg/kg weekly, and patients in Group II received acitretin in doses of 0.5 mg/kg daily. Patients were evaluated by modified PPPASI (m-PPPASI) score for palm and sole involvement at baseline, at two weekly intervals for the first 4 weeks and then four weekly for next 8 weeks. Treatment protocol was continued for a period till patient achieved 75% reduction in m-PPPASI from baseline or 12 weeks whichever was earlier. RESULTS: There was a statistically significant difference in reduction of m-PPPASI of patients on methotrexate at weeks 8 and 12. The mean m-PPPASI at week 8 was 15.38 ± 6.08 in methotrexate group and 17.23 ± 5.25 in acitretin group (P = 0.04). The mean m-PPPASI at week 12 was 10.30 ± 5.97 in methotrexate group and 12.40 ± 5.31 in acitretin group (P = 0.03). Marked improvement (m-PPPASI 75) was achieved in 12 (24%) patients in methotrexate group compared with 4 (8%) in acitretin group which was statistically significant (P = 0.029). Adverse events were generally mild and were seen in 14 patients in methotrexate group and 15 patients in acitretin group (P = 0.080). CONCLUSION: Methotrexate is relatively inexpensive, safe and efficacious drug for the treatment of psoriasis patients with significant palmoplantar involvement. Acitretin can be used as an alternative therapy and with a good safety profile.

Efficacy and safety of acitretin in three fixed doses of 25, 35 and 50 mg in adult patients with severe plaque type psoriasis: a randomized, double blind, parallel group, dose ranging study.

BACKGROUND: Acitretin is available for use in psoriasis since the late 1980s; however, there is no consensus on its optimum effective dose with acceptable side-effects. OBJECTIVE: To evaluate the efficacy and safety of acitretin in three fixed doses in adult patients with severe plaque type psoriasis. METHODS: This was a randomized, double blind, parallel group, dose ranging study. The study included patients of either gender (age range, 18-65 years) with severe chronic plaque type psoriasis. Of the 80 patients screened, 61 were randomly assigned to three groups: group A - 20 patients (acitretin 25 mg/day), group B - 20 patients (acitretin 35 mg/day) and group C - 21 patients (acitretin 50 mg/day) for 12 weeks. Forty-eight patients completed the study. The main outcome measure was change in Psoriasis Area Severity Index (PASI) score between the three groups from baseline to 12 weeks. RESULTS: After 12 weeks of therapy, the percentage reduction in the PASI score was 54%, 76% and 54% in acitretin 25, 35 and 50 mg/day group respectively. PASI 75 was achieved in 47%, 69% and 53% patients in acitretin 25, 35 and 50 mg/day groups respectively. The majority of adverse events were mucocutaneous, mild-to-moderate severity and dose dependent. CONCLUSIONS: Acitretin 35 mg/day was observed to be more efficacious compared to 25 mg/day and 50 mg/day dosing, whereas its safety profile is better than 50 mg/day dosing in the management of severe plaque type psoriasis in adult patients.

Efficacy and safety of rituximab treatment in Indian pemphigus patients.

BACKGROUND: Pemphigus is a potentially fatal autoimmune epidermal bullous disorder. Various treatment modalities have been described to treat pemphigus. In cases where the disease fails to respond to conventional therapy, rituximab has been shown to be effective. OBJECTIVE: To study the efficacy of rituximab in the treatment of resistant or severe pemphigus in Indian patients. METHODS: Patients with pemphigus were treated with intravenous rituximab 1000 mg in adults or 375 mg/m(2) body surface area in children by two doses, 15 days apart in this open labelled pilot study. Anti-desmoglein1 (anti-Dsg1) antibodies and anti-desmoglein3 (anti-Dsg3) antibodies were measured at the start of therapy and at the end of the follow-up period. The outcome was studied in terms of control of disease activity (CD), complete remission (CR), partial remission (PR) and time to disease control (TDC) as defined by the consensus statement from the International Pemphigus Committee. RESULTS: A total of 9 (90%) of 10 patients responded to the treatment. Three (30%) had CR of disease and were off all treatment. Four (40%) patients had CR and were on low dose oral prednisolone. Two (20%) patients had PR and were on low dose prednisolone. One patient died of sepsis. The mean TDC was 8 weeks. Response to treatment showed good correlation with index values of anti-Dsg1 antibody. Infusion-related angioedema and sepsis were seen as complications due to rituximab administration. CONCLUSION: Rituximab is effective in treating resistant and severe pemphigus in Indian patients. Acute complications can occur during rituximab infusion and require close monitoring.

Comparison between autologous noncultured epidermal cell suspension and suction blister epidermal grafting in stable vitiligo: a randomized study.

BACKGROUND: Vitiligo is an acquired disorder of pigmentation due to loss of epidermal melanocytes. Autologous noncultured epidermal cell suspension (NCES; a cellular grafting technique) and suction blister epidermal grafting (SBEG; a tissue grafting technique) are important established surgical modalities for the treatment of stable vitiligo. OBJECTIVES: To compare the two techniques, NCES and SBEG, for producing repigmentation in patients with stable vitiligo. METHODS: We randomized 41 patients with 54 stable vitiligo lesions into two groups. Patients in group 1 were treated with NCES, and those in group 2 with SBEG. They were evaluated 16 weeks postsurgery for the extent of repigmentation, colour match, change in Dermatology Life Quality Index (DLQI) score and patient satisfaction. RESULTS: The extent of repigmentation was excellent (showing 90-100% repigmentation) in 71% of lesions in the NCES group and 27% of lesions in the SBEG group (P = 0·002). Repigmentation ≥ 75% (good repigmentation) was observed in 89% of lesions in the NCES group and 85% of lesions in the SBEG group (P = 0·61). There was a significant decline in DLQI score in both the groups; the mean decline among groups differed significantly (P = 0·045). No significant difference was seen in colour match and pattern of repigmentation. Adverse effects were minimal. CONCLUSIONS: NCES is significantly better than SBEG and should be the preferred treatment for patients with stable vitiligo. To best of our knowledge, this is the first study directly comparing these two techniques.

Efficacy and safety of systemic methotrexate in two fixed doses of 10 mg or 25 mg orally once weekly in adult patients with severe plaque-type psoriasis: a prospective, randomized, double-blind, dose-ranging study.

BACKGROUND: Methotrexate (MTX) is the 'gold-standard' drug for the treatment of severe psoriasis. In the absence of any consensus on an optimum dose of MTX for psoriasis, there is wide variation in prescribing patterns between dermatologists, resulting in variable or delayed therapeutic effects. AIM: To identify the most effective fixed single weekly dose of oral MTX with acceptable side-effects in the treatment of severe plaque-type psoriasis. METHODS: This was a prospective, randomized, double-blind, parallel-group, dose-ranging study, which enrolled 60 patients of both genders (aged 18-62 years) with severe chronic plaque-type psoriasis. Patients were randomly assigned to one of two groups: group A was treated with MTX 10 mg once weekly, and group B was treated with 25 mg MTX once weekly. The main outcome measure was change in Psoriasis Area and Severity Index (PASI) between the two groups from baseline to 12 weeks. RESULTS: Of the 60 patients, 51 (85%) completed the 12-week study. At the end of the study, 24 patients (92.3%) in the MTX 25 mg group had achieved a 75% reduction in PASI (PASI 75) from baseline, compared with 18 patients (72%) in the MTX 10 mg group (P>0.05). Mean time in weeks to achieve PASI 75 was significantly shorter in the MTX 25mg group (7.92±1.91) than in the MTX 10mg group (9.47±2.29) (P<0.05). In addition, 20 patients (69%) in the MTX 25mg group achieved 100% reduction in PASI compared with 9 patients (30%) in the MTX 10mg group within 12weeks of the study period (P<0.01). Adverse effects were generally mild, and were noted in 43.1% of the 51 patients who completed the study, with no significant difference in frequency between the two groups, although they were less severe in the 10mg group. CONCLUSIONS: MTX 25mg is an effective dose as monotherapy for the treatment of severe psoriasis, whereas the 10mg dose is slow to act and less effective, but has a less severe side-effect profile.

The effect of topically applied corticosteroids on interleukin 1ß levels in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic recurrent disease of childhood. The therapeutics of AD needs to be more tailored given the new cytokine antibodies available. In this scenario we considered interleukin 1 beta (IL-1ß) levels before and after therapy with topical corticosteroids. OBJECTIVES: To measure the IL-1ß levels before and after treatment in patients with AD after 75% improvement in scoring for atopic dermatitis index. METHODS: Forty-five subjects with AD were treated with betamethasone ointment and their IL-1ß level was measured prior to and following treatment. RESULTS: The IL-1ß levels were raised during disease activity and following improvement they decreased in a statistically significant manner. Also the IL-1ß levels corresponded with the severity of disease activity. CONCLUSIONS: Newer modalities of therapy in the form of cytokine monoclonal antibodies should be studied in a larger scale in AD.

Chronic disfiguring facial lesions in an immunocompetent patient due to Exophiala spinifera: a case report and review of literature.

Exophiala spinifera is a rare fungus causing chromoblastomycosis or different types of phaeohyphomycosis (cutaneous, subcutaneous, disseminated and cyst phaeohyphomycosis). We report a case of a young male with phaeohyphomycosis due to E. spinifera, who had multiple itchy painful papular lesions disfiguring his face for 4 years. His diagnosis was delayed and had received antibacterial and antileishmanial therapy elsewhere without any improvement. While he reported to our hospital, the histopathology of the biopsy collected from the lesion demonstrated acute on chronic inflammation with granuloma formation and darkly pigmented fungal elements. The isolate grown on culture was identified as E. spinifera on the basis of morphological characters. The identification of the isolate was further confirmed by sequencing of the ITS region of ribosomal DNA. After treatment with oral itraconazole, he had marked clinical improvement.

Role of apoptosis and melanocytorrhagy: a comparative study of melanocyte adhesion in stable and unstable vitiligo.

BACKGROUND: Apoptosis and melanocytorrhagy have been proposed as mechanisms of melanocyte disappearance although there are few controlled studies. OBJECTIVES: We undertook this project to study melanocyte morphology and adhesion defects in patients with stable and unstable disease in controls. METHODS: In this comparative study we included seven patients with stable disease and seven patients with unstable vitiligo. We cultured perilesional skin melanocytes from these patients with stable and unstable vitiligo and studied for morphological changes, adhesion to collagen type IV and caspase 3 expression. Melanocytes were also treated with okadaic acid and annexin V expression was then checked and compared between controls and patients with stable and unstable vitiligo. RESULTS: Perilesional skin melanocytes from patients with unstable vitiligo revealed some significant morphological changes. Melanocytes from unstable vitiligo showed significantly low adhesion to collagen type IV compared with control and stable vitiligo melanocytes. Our results showed that caspase 3 and annexin V staining was significantly greater in melanocytes cultured from unstable vitiligo compared with the control. CONCLUSIONS: In this study we demonstrated that melanocytes in the patients with unstable vitiligo were in their detachment phase, which ultimately leads to apoptosis of these cells, whereas melanocytes cultured from controls and from patients with stable vitiligo were morphologically normal without any adhesion defects. These morphological and adhesion findings support the theory of melanocytorrhagy as the primary defect underlying melanocyte loss in unstable vitiligo.

Altered levels of Ets-1 transcription factor and matrix metalloproteinases in melanocytes from patients with vitiligo.

BACKGROUND: Vitiligo is characterized by the loss of functional melanocytes from the epidermis. Repigmentation in vitiligo is initiated by activation, proliferation and migration of melanoblasts from the outer root sheath of hair follicles, or melanocytes from the border area of vitiligo lesions, into the depigmented epidermis. Cell migration plays a crucial role during repigmentation in vitiligo. OBJECTIVES: To investigate the role of matrix metalloproteinases (MMPs) and their transcription factor Ets-1 in vitiligo. METHODS: Skin biopsies were taken from 15 patients with vitiligo and six controls to culture melanocytes from clinically active perilesional and normal skin. Expression of MMP-1, MMP-2, MMP-9 and Ets-1 was examined by reverse transcriptase-polymerase chain reaction analysis. Expression of Ets-1 was also confirmed with Western blot analysis. Activity of MMP-2 and MMP-9 was assessed using gelatin zymography. RESULTS: The activity of MMP-2 and MMP-9 was significantly lower in patients with vitiligo compared with the controls. The expression of MMP-2 and MMP-9 was also significantly lower in patients with vitiligo. There was no expression of Ets-1 transcription factor at either the transcriptional or translational level in melanocytes cultured from patients with vitiligo. CONCLUSION: The absence of a basal level of expression of Ets-1 significantly decreases the expression and activity of MMP-2 and MMP-9. Significant decreases in MMP-2 and MMP-9 activity could possibly reduce the migration of melanocyte precursors (melanoblasts) from the outer root sheath of hair follicles or migration of melanocytes from the border of vitiligo lesions into clinically depigmented epidermis which is crucial to the repigmentation of vitiliginous skin.