Halo naevi and leukotrichia are strong predictors of the passage to mixed vitiligo in a subgroup of segmental vitiligo

Background Until now, segmental vitiligo has been considered as a stable entity and mixed vitiligo, the association of segmental and nonsegmental vitiligo, has been reported rarely. Objectives The aim of this study was to search for factors associated with the generalization of vitiligo in patients with segmental vitiligo. Patients and methods This was a prospective observational study conducted in the vitiligo clinic of the Department of Dermatology of Bordeaux, France. The Vitiligo European Task Force questionnaire was completed for each patient attending the clinic with a confirmed diagnosis of segmental vitiligo after exclusion of other forms of vitiligo (focal, mucosal, not classifiable.) Thyroid function and antithyroid antibodies were screened if not obtained in the previous year. Results One hundred and twenty‐seven patients were recruited: 101 had segmental vitiligo and 26 had segmental vitiligo that evolved into mixed vitiligo; 56 were male and 71 were female. Most patients had onset of segmental vitiligo before the age of 18. When conducting multivariate analysis, we found the following to be independent factors associated with the evolution of patients’ disease from segmental vitiligo to mixed vitiligo: initial percentage of body surface involvement of the segment > 1% [odds ratio (OR) 15·14, P = 0·002], the presence of halo naevi (OR 24·82, P = 0·0001) and leukotrichia (OR 25·73, P = 0·0009). Conclusions Halo naevi association and leukotrichia at first consultation in segmental vitiligo are risk factors for the progression of segmental vitiligo to mixed vitiligo. In addition, this progression of segmental vitiligo to mixed vitiligo carries a stronger link if initial segmental involvement is situated on the trunk.     

Prognostic value and clinical significance of halo naevi regarding vitiligo

Background Vitiligo and halo naevi can present together or separately. Whether they are different entities remains unclear. Objectives To assess the clinical significance of halo naevi, both with respect to the future development of vitiligo, and to the clinical profile and course of vitiligo. Methods In total, 291 patients were included in this study: patients with only halo naevi (group 1; n = 40), patients with generalized vitiligo without halo naevi (group 2; n = 173) and patients with generalized vitiligo with halo naevi (group 3; n = 78). Results Patients with only halo naevi (group 1) reported significantly less associated autoimmune disease (P = 0·001), were less likely to have a family history of vitiligo (P = 0·013) and were less likely to have presence of Koebner phenomenon (P < 0·001) compared with patients with generalized vitiligo (groups 2 + 3). Multiple halo naevi (≥ 3) were significantly more frequently observed (P = 0·002) in patients from group 1 compared with patients from group 3. In group 3, halo naevi were reported prior to the development of vitiligo in 61% (mean ± SD time interval of 33·7 ± 5·17 months). No significant correlation was observed between the presence of halo naevi and the extent, activity or subtype of vitiligo. However, halo naevi in patients with vitiligo significantly reduced the risk for associated autoimmune diseases, and age at onset of vitiligo was significantly lower compared with patients with vitiligo without halo naevi (P < 0·001). Conclusions Our results support the hypothesis that halo naevi can represent a distinct condition. In a subset of patients, the occurrence of halo naevi may be an initiating factor in the pathogenesis of vitiligo.     

The angiotensin‐converting enzyme gene insertion/deletion polymorphism in Indian patients with vitiligo: a case–control study and meta‐analysis

Background  Vitiligo is a common, acquired, idiopathic depigmenting skin disorder. Although the exact pathogenesis remains unknown, genetic susceptibility and autoimmune responses play a role in vitiligo development. Previous studies have suggested that the D allele of the insertion/deletion (I/D) polymorphism of the angiotensin‐converting enzyme (ACE) gene is associated with vitiligo in Indians and Koreans. Furthermore, significantly higher serum ACE levels have been demonstrated in patients with some autoimmune and autoinflammatory disorders. Objectives  The objectives were to investigate any association between the ACE I/D polymorphism and vitiligo susceptibility in an Indian population, and to compare serum ACE levels in patients with vitiligo and healthy subjects. Methods  The ACE I/D genotypes of 79 patients with vitiligo and 100 normal individuals were determined by polymerase chain reaction amplification. A meta‐analysis was done to compare the distribution of the ACE I/D alleles and genotypes in the current and three previous studies. Serum ACE levels were evaluated by enzyme‐linked immunosorbent assay. Results  A significant increase in the frequency of the ACE I/D D allele was evident in patients with vitiligo in both the case–control study [P = 0·005; odds ratio (OR) 1·87; 95% confidence intervals (CI) 1·22–2·85] and the meta‐analysis (P = 0·044; OR 1·44; 95% CI 1·01–2·06). Serum ACE levels were significantly increased in patients with vitiligo compared with healthy subjects (P < 0·0001). Conclusions  In agreement with earlier reports, the ACE I/D D allele is associated with vitiligo susceptibility in the Indian population. The significantly elevated serum ACE levels in our cohort of patients with vitiligo concur with those previously found in patients with some other autoimmune diseases.     

Willingness-to-pay and quality of life in patients with vitiligo

Background Vitiligo is a chronic pigmentary disorder of the skin, affecting 1–2% of the general population. Although not life threatening, vitiligo may considerably influence patients’ health‐related quality of life (QoL) and psychological well‐being. Willingness‐to‐pay (WTP) is a construct reflecting disease burden and QoL reduction which has not yet been used in vitiligo. Objectives To assess the WTP and the QoL of patients with vitiligo. Methods Patients with vitiligo were included in a nationwide German postal survey. WTP was assessed by two standardized items, and QoL was evaluated using the Dermatology Life Quality Index (DLQI) and the EuroQol (EQ‐5D) questionnaire. QoL data were compared with n = 1511 patients from a national survey on psoriasis. Results The questionnaire was completed by 1023 patients (71·5% women, mean age 44·4 years, mean disease duration 20·3 years) with vitiligo. The mean DLQI was 7·0 (7·5 in women, 5·5 in men) compared with 8·6 in psoriasis. Of the patients with vitiligo, 24·6% had a DLQI > 10 which indicates severe QoL reductions, compared with 34·1% in patients with psoriasis. The highest mean DLQI value was observed in the patient group aged 20–29 years. EQ‐5D mean score was 83·6 compared with 75·3 in psoriasis. Of the patients with vitiligo, 32·9% would pay more than 5000 Euro in order to achieve complete disease remission. WTP was highest among middle‐aged patients (30–60 years). There was a significant correlation between DLQI scores and WTP (χ² = 65·43, P < 0·001). Moreover, WTP significantly correlated with duration of disease, and with body surface area affected (P < 0·001). Conclusions Vitiligo causes substantial disease burden as reflected by QoL impairment and high WTP, especially in women. These results should draw the attention of physicians to this disease, as appropriate education and treatment are likely to improve the QoL of patients with vitiligo and may support patients’ compliance and empowerment.     

Analysis of interleukin-10 levels in lesions of vitiligo following treatment with topical tacrolimus

Background Vitiligo is an acquired dermatological condition that is characterized by depigmentation of patches of skin. It is relatively common, occuring in about 0·38–0·50% of the general population, and can engender significant cosmetic disfigurement and psychological sequelae in the affected individual. Recent studies demonstrate that topical tacrolimus (Protopic^®; Astellas, Markham, ON, Canada) is efficacious in the treatment of vitiligo. We propose that the successful treatment of vitiligo with topical tacrolimus involves the unique immunosuppressive actions of the T lymphocyte T‐helper (Th) 2 cytokine, interleukin (IL)‐10. Objectives We aimed to monitor clinical changes in lesions of vitiligo treated with topical tacrolimus 0·1% ointment and quantify IL‐10 cytokine levels in nonvitiliginous skin, as well as lesions of vitiligo before and following topical tacrolimus therapy. Methods Clinical evaluation of lesions of vitiligo on the basis of surface area and follicular repigmentation under Wood’s lamp was performed in 20 enrolled adult patients. Biopsy specimens were obtained from nonvitiliginous skin, as well as lesions of vitiligo before and following topical tacrolimus therapy. Specimens were processed and analysed for expression of IL‐10 using the method of enzyme‐linked immunosorbent assay. Results A statistically significant mean ± SEM decrease in vitiligo lesion size of 41·0 ± 5·2% was observed following 3 months of treatment. A pattern of follicular repigmentation was noted by the third month of treatment for all patients completing the study. In addition, there was a statistically significant difference between IL‐10 expression in vitiligo lesions following treatment for 3 months with topical tacrolimus compared with untreated vitiligo lesions (P = 0·017) and normal skin (P = 0·004). Conclusions These results confirm that topical tacrolimus is an effective treatment for vitiligo. We propose that topical tacrolimus increases IL‐10 expression in vitiligo lesions, and thereby inhibits melanocyte destruction triggered by unchecked Th1 pathways in vitiligo.     

Multivariate analysis of factors associated with early-onset segmental and nonsegmental vitiligo: a prospective observational study of 213 patients

Background Although mixed forms have been described recently, segmental (SV) and nonsegmental vitiligo (NSV) are considered as clinically distinct. However, limited epidemiological data are available to help distinguish associated factors, and recent genome‐wide association studies have been restricted to NSV. The higher prevalence of SV in children is helpful when comparing the two major presentations of the disease. Objective To compare factors associated with SV and NSV, especially for markers of autoimmunity or autoinflammation. Methods We conducted a single‐centre prospective observational study in patients aged 17 years or under with a confirmed diagnosis of SV or NSV at the vitiligo clinic between 1 January 2006 and 1 July 2010. The Vitiligo European Task Force questionnaire was completed for each patient, and thyroid function and antithyroid antibodies were screened if not obtained in the previous year. Other forms of vitiligo (focal, mucosal, not classifiable) were excluded. Results A total of 213 children were included, 142 with NSV, 59 with SV and 12 with mixed vitiligo. There was no significant statistical difference for sex or age at onset between patients with SV and NSV. Halo naevi were significantly more frequent in NSV than in SV [odds ratio (OR) 7·58, P < 0·01). Patients with NSV more frequently had a positive family history of vitiligo (OR 2·25, P = 0·02) and a marked familial autoimmunity background (OR 2·22, P = 0·01). Conclusions Our study clearly shows that features of inflammation (pruritus)/autoimmunity (halo naevi, thyroid antibodies) are strongly linked to NSV, together with a familial background of vitiligo and autoimmunity.     

Is there a relationship between homocysteine and vitiligo? A pilot study

Background Pigmentary dilution is observed in patients with homocystinuria. Therefore, it is possible that an increase of local homocysteine (Hcy) interferes with normal melanogenesis and plays a role in the pathogenesis of vitiligo. Vitamin B₁₂ and folic acid, levels of which are decreased in vitiligo, are important cofactors in the metabolism of Hcy. Consequently, a nutritional deficiency in either of these two vitamins will result in an increase in homocysteine in the circulation, a finding that we expect to find in vitiligo. Objective To determine the level of Hcy in the blood of patients with vitiligo as a first step in revealing if it has any relationship with the pathogenesis of vitiligo and consequently if this will have an impact on the treatment of vitiligo. Methods Twenty‐six patients of both sexes with vitiligo (age range 20–50 years, mean 31·4 ± 8·09) and 26 age‐matched healthy controls were included in the study. After excluding factors that may affect serum Hcy levels, blood samples from patients and controls were obtained for homocysteine determination by enzyme immunoassay. Results The mean serum level of Hcy was significantly higher in patients with vitiligo than in controls (21·61 ± 13·28 vs. 13·1 ± 4·88 μmol L^?1; P < 0·001). The Hcy level was significantly higher in male patients than in female patients (28·67 ± 15·95 vs. 15·56 ± 6·2 μmol L^?1; P < 0·001) and in male controls compared with female controls (15·07 ± 4·61 vs. 12·05 ± 4·82 μmol L^?1; P < 0·001). The homocysteine level was related to the activity of vitiligo and was significantly higher in patients with progressive disease than in controls (25·4 ± 14·99 vs. 13·1 ± 4·88 μmol L^?1; P < 0·001). No significant difference in Hcy levels was found between either untreated vitiligo patients (22·77 ± 13·36 μmol L^?1) or patients receiving ultraviolet therapy (20·45 ± 13·73 μmol L^?1) and the total patient group (21·62 ± 13·28 μmol L^?1). Conclusion An elevated homocysteine level may be a precipitating factor for vitiligo in predisposed individuals. In view of the biological role of vitamin B₁₂ and folic acid in Hcy metabolism, we present our recommendations regarding the investigation and treatment of this common disease.     

Long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo: effect of disease activity

Background Punch grafting is a simple and frequently used technique for the treatment of stable vitiligo, resistant to medical therapy. However, studies reporting long‐term results are exceptional. Objectives To evaluate the long‐term results of 2‐mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo. Methods We studied a prospective cohort study involving 61 patients (25 male, 36 female) with vitiligo vulgaris and nine patients (all male) with segmental vitiligo who underwent 2‐mm punch grafting more than 3 years ago. The main outcome measure was the degree of repigmentation of a single transplanted lesion as measured with a digital image analysis system with a mean follow‐up of 5·2 years. Results In patients with vitiligo vulgaris, 17 lesions (28%) showed excellent, 14 lesions (23%) showed good, 14 lesions (23%) showed fair and 16 lesions (26%) showed poor repigmentation. In patients with segmental vitiligo, seven of nine lesions (78%) showed excellent repigmentation. A cobblestone‐like effect was observed in 19 of 70 patients (27%). Disease activity after punch grafting was reported in 94% of patients with poor repigmentation but in only 18% of patients with excellent repigmentation (χ² test, P < 0·0005). Patients who reported disease activity after transplantation had a lower mean repigmentation than those who did not report disease activity (77% vs. 39%, P < 0·05). Conclusions Two‐millimetre punch grafting in vitiligo is an effective surgical procedure with long‐lasting effect. To prevent a cobblestone‐like effect, we advise the use of smaller grafts (1–1·2 mm). Disease activity after grafting, localization and type of vitiligo, prior ultraviolet B treatment and a Koebnerized donor site influence the long‐term outcome of punch grafting and should be taken into account in the selection of patients eligible for this treatment.     

A double-blind, randomized, placebo-controlled trial of topical tacrolimus 0·1% vs. clobetasol propionate 0·05% in childhood vitiligo

Background Both clobetasol propionate 0·05% (CP 0·05%) and tacrolimus 0·1% (T 0·1%) ointments have been shown to be efficacious and safe in treating vitiligo in the paediatric population. Objectives To assess efficacy and safety of these two therapies compared with each other and with placebo. Methods In this prospective study, children aged 2–16 years with vitiligo, stratified into ‘facial’ (n = 55) and ‘nonfacial’ (n = 45) groups, were randomized into three arms: CP 0·05% ointment (n = 30), T 0·1% ointment (n = 31) and placebo (n = 29) for 6 months. Successful repigmentation, defined as > 50% improvement, was evaluated by comparing photographs taken at baseline and at 2, 4 and 6 months. Results In the facial group, 58% of the CP 0·05% group responded successfully compared with 58% of the T 0·1% group, and in the nonfacial group, 39% of the CP 0·05% group responded compared with 23% of the T 0·1% group (P > 0·05). There was a significant difference in response between the CP 0·05% group vs. placebo (P < 0·0001) and the T 0·1% group vs. placebo (P = 0·0004). Spontaneous repigmentation was evaluated as 2·4%. No significant clinical adverse events were noted in any group. Conclusions Both CP 0·05% and T 0·1% ointments offer similar benefit in paediatric vitiligo, both facial and nonfacial. The facial lesions responded faster than the nonfacial ones.     

Evaluation of different methods in the follow-up of patients with indolent types of primary cutaneous lymphomas

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.     

Study of clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo undergoing melanocyte transplantation

Background Stability is considered the most important parameter before performing any melanocyte transplantation procedure in vitiligo; however, current criteria rely on the history given by the patients. Objective  This study was undertaken to determine the clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo to facilitate better patient selection for melanocyte transplantation and to understand immunological mechanisms for disease activity. Methods  Thirty‐three patients with generalized vitiligo with < 10% body surface area involved were allocated to three clinical stability groups: Group 1 (stability > 3 months but < 1 year), Group 2 (≥ 1 year but < 2 years) and Group 3 (≥ 2 years). Melanocyte transplantation was done using suction blister epidermal grafting (SBEG) on a single patch. Blood was drawn for catalase estimation from all patients and from 10 healthy control subjects. A 3‐mm punch biopsy was taken on the day of transplantation from the margin of the macule in the first five patients in each group for the immunohistochemistry of CD4, CD8, CD45RO, CD45RA and FoxP3. Those with ≥ 75% repigmentation at 6 months were labelled as responders. Results  The success rate was 0% in Group 1, 37·5% in Group 2 and 77·8% in Group 3. The difference in the success rate between the groups was statistically significant (P = 0·005). The median period of stability was significantly higher in the responders compared with that in the nonresponders (P = 0·001). Catalase levels were not significantly different between patients in the three groups of cases and in controls, or between responders and nonresponders. Lesional CD8 cells were significantly higher in Group 1 compared with Group 3. The percentages of CD8 and CD45RO cells were significantly higher in the nonresponders compared with the responders. Conclusion Along with clinical stability, the proportion of CD8 and CD45RO cells in skin biopsies might help to determine the stability of the disease and thereby predict the success of transplantation.     

A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis

Background Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis. Objectives To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor‐inhibitor therapy. Methods Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5–15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Results In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician’s Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm. Conclusions Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.     

Randomized controlled trial comparing the effectiveness of 308-nm excimer laser alone or in combination with topical hydrocortisone 17-butyrate cream in the treatment of vitiligo of the face and neck

Background Vitiligo is a pigmentary disorder which may have disfiguring consequences. Its treatment remains a challenge. Objectives We designed a parallel‐group randomized controlled trial to compare the effectiveness of 308‐nm excimer laser alone or in combination with topical hydrocortisone 17‐butyrate cream in patients with vitiligo unresponsive to previous treatment with topical steroids or narrow‐band ultraviolet (UV) B phototherapy. Methods Consecutive patients aged 18–75 years with nonsegmental vitiligo localized on the face and/or neck lacking response to previous conventional treatment were eligible. In total, 84 patients (44 women and 40 men, mean age 44 years) were randomized to 308‐nm excimer laser phototherapy twice weekly alone or in combination with topical hydrocortisone 17‐butyrate cream twice daily for three periods of 3 weeks followed by a 1‐week steroid‐free interval. The primary outcome was a reduction of at least 75% of the overall lesional areas as judged by automatic image analysis on reflected UV photographs, conducted blind to treatment assignment, at 12 weeks compared with baseline. Secondary outcomes were clearance, and improvements on Physician’s Global Assessment (PGA) and Skindex‐29 scores. Results A total of 76 (90%) patients completed the study. In an intention‐to‐treat analysis, seven [16·6%; 95% confidence interval (CI) 5·3–27·8%] patients in the excimer monotherapy arm and 18 (42·8%; 95% CI 27·8–57·8%) in the combination arm showed ≥ 75% reduction of vitiligo lesions at 12 weeks (χ² test 6·89, P = 0·0087). Clearance was observed in two (4·7%; 95% CI 1·6–11·2%) and nine (21·4%; 95% CI 9·0–33·8%) patients, respectively (Fisher’s exact test P = 0·04). A significant difference also emerged for PGA scores, while no difference was documented for Skindex‐29. Conclusions Recalcitrant vitiligo of the face and neck may benefit from the combination of excimer laser phototherapy with topical hydrocortisone 17‐butyrate cream.     

Recurrence and risk factors in cured patients with vitiligo: A real-life single-center retrospective study

Background

The risk of recurrence after successful repigmentation in vitiligo has attracted attention from both patients and clinicians.

Objectives

The recurrence rate and risk factors in cured patients with vitiligo were analyzed to improve clinical prevention and treatment.

Methods

Clinical records of 76 patients with vitiligo who demonstrated at least 80% repigmentation were analyzed retrospectively. Single-factor analysis of variance and binary logistic regression analysis was employed to screen the risk factors of vitiligo recurrence.

Results

Among the 76 cured patients, 26 relapsed (total recurrence rate of 34.2%). Among these, 20 relapsed within one year (recurrence rate of 26.3%). Single-factor analysis of variance revealed significant differences (p < 0.05) with the age of onset (yr), distribution of onset, and oral traditional Chinese medicine (TCM) intake between the recurrence and nonrecurrence groups. Binary logistic regression analysis displayed that the age of onset (yr) (p = 0.015, OR = 1.051), distribution of onset (p = 0.046, OR = 0.194), and oral TCM (p = 0.018, OR = 4.360) are significant risk factors for vitiligo recurrence.

Conclusion

A total relapse rate of 34.2% was observed in cured vitiligo patients. The age of onset (yr), distribution of onset, and oral TCM are risk factors for vitiligo recurrence. The necessary interventions should be considered on these factors for reducing the recurrence rate of vitiligo.     

A preliminary report on the role of some immunologic factors in persistence of chronic tinea pedis

The phenotypic distribution of HLA antigens was investigated in 29 patients with chronic dermatophyte infections and 558 age controls using a microcytoxicity assay. Statistical analysis of data indicated that there was an increased frequency of HLA antigen A26, and AW33. A26 was present in 24% of the patients and 6% of the controls (P= 0·0006). AW₃₃ was present in 14% of the patients and 2% of the controls (P= 0·0002). Intercellular substance (ICS) antibody and IgE assay were performed on these patients. Thirty-four per cent of the patients produced an ICS antibody and had an increased incidence of A26 (P= 0·002). Sixty-six per cent of the patients who did not produce an anti-ICS antibody had an increased frequency of HLA antigen AW₃₃ (P= 0·0002). DR antigens were studied in 26 patients. DR4 was found in 46% of patients but this was not statistically significant. The frequency of the antigen increased to 83% (corrected P value 0·049) in patients with a personal and/or family history of atopy and increased to 86% in patients with high IgE levels (corrected P value 0·016). It appears that several host factors may play an important role in determining and/or perpetuating chronic tinea pedis infection.     

Vitiligo and depression: a systematic review and meta‐analysis of observational studies

Vitiligo is a common depigmenting disorder with profound psychosocial impacts. Previous observational studies have suggested a link between vitiligo and psychiatric morbidity, such as depression. However, variability in study design makes it difficult to quantify accurately the relationship between vitiligo and depression. We aimed to investigate the underlying prevalence and risk of depression among patients with vitiligo. A comprehensive search of MEDLINE, Embase and the Cochrane Library was conducted. Cross‐sectional, case–control or cohort studies that assessed the prevalence of depression among patients with vitiligo or the relationship between vitiligo and depression were included. DerSimonian and Laird random‐effects models were utilized to calculate the pooled prevalence and relative risks. Publication bias was evaluated by funnel plots and Egger's tests. Twenty‐five studies with 2708 cases of vitiligo were included. Based on diagnostic codes, the pooled prevalence of depression among patients with vitiligo was 0·253 [95% confidence interval (CI) 0·16–0·34; P < 0·001)]. Using self‐reported questionnaires, the pooled prevalence of depressive symptoms was 0·336 (95% CI 0·25–0·42; P < 0·001). The pooled odds ratio of depression among patients with vitiligo was 5·05 vs. controls (95% CI 2·21–11·51; P < 0·001). Moderate‐to‐high heterogeneity was observed between the studies. Patients with vitiligo were significantly more likely to suffer from depression. Clinical depression or depressive symptoms can be prevalent, with the actual prevalence differing depending on screening instruments or, possibly, geographical regions. Clinicians should actively evaluate patients with vitiligo for signs/symptoms of depression and provide appropriate referrals to manage their psychiatric symptoms accordingly.     

A clinical trial and molecular study of photoadaptation in vitiligo

Background Photoadaptation to ultraviolet (UV) B phototherapy is due to both pigmentary and nonpigmentary influences. Objectives To measure photoadaptation in vitiliginous skin and to compare it with normal pigmented skin. Methods Seventeen patients with Fitzpatrick skin phototypes III–VI with vitiligo received six to nine UVB treatments, two to three times weekly. Minimal erythema dose (MED) testing was done at baseline and after all treatments; the percentage change in MED was analysed as a measure of photoadaptation. The percentage decrease in cyclobutane pyrimidine dimers (CPDs) over 24 h after a single exposure of 1 MED was analysed on vitiliginous and normal skin. Results The mean ± SD percentage change in MED from before to after treatments was: treated vitiliginous skin 28·5 ± 39·9% (P = 0·015), treated normal skin 35·9 ± 49·9% (P = 0·015), untreated vitiliginous skin 11·9 ± 22·6% (P =0·070), untreated normal skin 25·1 ± 41·3% (P = 0·041). Of these patients, two‐thirds had a positive percentage change in MED (photoadaptation). The mean amount of CPDs induced per megabase of DNA immediately after exposure was significantly higher in vitiliginous skin. The mean ± SD percentage decrease in CPDs (rate of repair) in 24 h was 35·7 ± 26·8% in vitiliginous skin (P = 0·027) and 46·2 ± 19·5% in normally pigmented skin (P = 0·001); no difference was noted in the repair in vitiliginous skin compared with normal skin (P = 0·4). Conclusions Photoadaptation in vitiliginous and normal skin was observed in two‐thirds of patients. Vitiliginous skin had significantly more CPDs following UVB exposure; the rate of repair of UVB‐induced DNA damage was equivalent to that in normal skin.     

Combination treatment by 10 600 nm ablative fractional carbon dioxide laser and narrowband ultraviolet B in refractory nonsegmental vitiligo: a prospective, randomized half-body comparative study

Background Vitiligo is a common acquired depigmentation disorder caused by the loss of melanocytes. Despite the numerous treatment modalities available for vitiligo, responses to treatment are still unsatisfactory. For this reason, new treatment modalities and approaches are needed. Objectives To investigate the effects of fractional carbon dioxide (CO₂) laser therapy followed by systemic narrowband ultraviolet B (NB‐UVB) phototherapy on nonsegmental vitiligo (NSV) as a prospective and randomized left‐right comparative study. Methods Ten patients with NSV who presented symmetrical vitiligo lesions with no further improvement despite more than 1 year of conventional treatment were enrolled. Two sessions of half‐body fractional CO₂ laser therapy were performed at a 2‐month interval. NB‐UVB phototherapy was then administered to the entire body 5 days after each fractional laser treatment twice a week, increasing the dose incrementally by 15% at each session. Objective clinical assessments were made by two blinded dermatologists using a quartile grading scale, and the patients’ overall satisfaction was evaluated using a 10‐point visual analogue scale. Results Two months after the last treatment, mean improvement scores, assessed by physicians, were significantly higher for those treated with half‐body fractional CO₂ laser therapy followed by NB‐UVB phototherapy, compared with those treated with NB‐UVB alone (P = 0·034). In addition, according to subjective assessment, the half‐body laser treatment followed by NB‐UVB showed significantly higher improvements compared with NB‐UVB treatment alone (P = 0·023). Noticeable adverse events, such as infection, scarring and Koebner phenomenon, were not found in any patient. Conclusions This study suggests that fractional CO₂ laser therapy followed by NB‐UVB phototherapy could be used effectively and safely as an alternative modality for the treatment of refractory vitiligo.