Pre- vs. post-pubertal onset of vitiligo: multivariate analysis indicates atopic diathesis association in pre-pubertal onset vitiligo

Background Limited epidemiological data exist that compare clinical features of pre‐ and post‐pubertal nonsegmental vitiligo. Objectives To compare factors associated with pre‐ and post‐pubertal onset vitiligo. Patients and methods A prospective observational study was conducted of patients with vitiligo attending the clinic between 1 January 2006 and 1 July 2011. The Vitiligo European Task Force questionnaire was completed for each patient and thyroid function and antithyroid antibodies were screened. Other forms of vitiligo (segmental, focal, mucosal, not classifiable) were excluded. Results A total of 679 patients were included; 422 had post‐pubertal and 257 pre‐pubertal onset of vitiligo. Vitiligo universalis was seen only in post‐pubertal onset. In univariate analysis, there was no significant statistical difference for sex, Koebner phenomenon or disease activity between both groups; thyroid disease or presence of thyroid antibodies was more frequent in post‐pubertal onset [odds ratio (OR) 0·31, P < 0·003] whereas atopic dermatitis was more often associated with or preceding pre‐pubertal onset (OR 2·42, P = 0·006). In multivariate analysis, halo naevi, family history of vitiligo, premature hair greying, atopic dermatitis and previous episode of spontaneous repigmentation were independently associated with pre‐pubertal onset. In contrast, stress as onset factor, personal history of thyroid disease and acrofacial type were associated with post‐pubertal onset. Conclusions Pre‐pubertal onset vitiligo is strongly associated with personal and family history of atopy, suggesting that the predisposing immune background in vitiligo is not limited to autoimmunity, as also noted in alopecia areata. This study also suggests reconsidering the epidemiological data on sex ratio in vitiligo.     

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.     

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.     

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.     

Psoriasis and melanocytic naevi: does the first confer a protective role against melanocyte progression to naevi?

Background Some of the cytokines that have effects on melanogenesis are also reported to be involved in psoriasis. Objectives We therefore studied the relationship between psoriasis and melanocytic naevi. In particular, the aim of our study was to investigate the number of melanocytic naevi in patients with psoriasis vs. controls. Methods We performed a prospective case–control study, analysing 93 adult patients with psoriasis and 174 adult aged‐matched controls. For each participant a questionnaire was completed to establish personal data, personal medical history, and personal and familial history of skin cancer and psoriasis. We analysed interleukin (IL)‐1α, IL‐6 and tumour necrosis factor (TNF)‐α gene expression at the peripheral blood mononuclear cell level in patients with psoriasis and in controls. Results In our study, patients with psoriasis presented a lower number of areas with naevi in comparison with controls (P < 0·0001). Nobody had ever had squamous cell carcinoma or melanoma in the psoriatic group; moreover, there was a significant difference in familial history of melanoma between the two groups (none in the psoriatic group vs. 8% in the control group; P < 0·05). IL‐1α, IL‐6 and TNF‐α expression levels were higher in patients with psoriasis. Conclusions People with psoriasis had fewer melanocytic naevi. This suggests that the proinflammatory cytokine network in psoriasis skin might inhibit melanogenesis, melanocyte growth and/or progression to naevi.     

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.     

Prevalence and distribution of melanocytic naevi on the scalp: a prospective study

Background Few studies have examined the incidence and characteristics of naevi on the scalp. Most studies of scalp naevi have been performed in children, whose incidence of scalp naevi is relatively high, at about 0·5–11·7% of the total body count of common naevi. Objectives To investigate the prevalence and distribution of scalp melanocytic naevi in patients of all ages. To our knowledge, ours is the first study to analyse in detail the relationships between melanocytic naevi on the scalp and total body naevi and total body atypical naevi. Methods We conducted a prospective study of patients visiting the dermatology outpatient clinic at the University of Florence, for examinations unrelated to the presence of naevi or melanoma. The study enrolled 795 subjects (417 females; 52·4%), with a median age of 35 years (range 4–80). Results The number of melanocytic naevi on the scalp increased significantly (r = 0·2057, P = 0·0008) as the number of total body melanocytic naevi increased and a correlation was found between the number of clinically atypical total body naevi and the number of scalp naevi. Relatively few naevi (15·5%) were located at the frontal region compared with other regions of the scalp, although the frontal region is more exposed to ultraviolet (UV) rays. Compared with subjects without alopecia, whose hair shields the scalp from UV rays, subjects with androgenetic alopecia showed no significant increase in number of scalp naevi. Conclusions Despite practical difficulties, early diagnostic screening for melanoma or screening during follow‐up examination for previous melanoma should involve examination of the entire skin surface, scalp included.     

Association of UVRAG polymorphisms with susceptibility to non‐segmental vitiligo in a Korean sample

Please cite this paper as: Association of UVRAG polymorphisms with susceptibility to non‐segmental vitiligo in a Korean sample. Experimental Dermatology 2010; 19 : e323–e325. Abstract: Autoimmune, self‐destructive, oxidative stress and genetic theories have been proposed for the pathogenesis of vitiligo. Autophagy is essential for cellular homeostasis and is implicated in many pathophysiological conditions such as cancer, response to oxidative stress and autoimmunity. The ultraviolet (UV) radiation resistance‐associated gene (UVRAG) activates the Beclin1‐PI(3)KC3 complex, promoting autophagy. To evaluate whether UVRAG polymorphisms are associated with non‐segmental vitiligo (NSV) patients in a Korean sample, we conducted a case–control association study of 225 NSV patients and 439 matched healthy controls. A total of five single nucleotide polymorphisms (SNPs) of UVRAG were selected for analysis. Among these, two SNPs (rs1458836, rs7933235) showed significant genotypic differences between the NSV patient group and the control group. These two SNPs were located within a strong linkage disequilibrium (LD) block. In addition, the haplotype of the UVRAG polymorphism was associated with NSV. This study suggests a possible association between UVRAG and NSV susceptibility.     

Parental sun-protective regimens and prevalence of common melanocytic naevi among 7-year-old children in Sweden: changes over a 5-year period

Background Common melanocytic naevi and cutaneous malignant melanoma share a common risk profile, influenced by ultraviolet radiation exposure. A high density of common melanocytic naevi correlates with an increased lifetime risk of developing cutaneous malignant melanoma. Effective strategies for sun protection, starting in early childhood, are considered of great importance to reduce the steadily rising melanoma trend. Objectives To investigate the 5‐year changes in sun tanning habits, sun‐protective regimens and density of common melanocytic naevi between two age‐standardized populations of children. Methods Population‐based cross‐sectional study performed among 7‐year‐old children in southern Sweden in 2002 and 2007. The parents answered a questionnaire and all children were examined by the same, trained research nurse. Results In total, 1190 children were enrolled: 681 in 2002 and 509 in 2007. The results showed that sun‐protective regimens, such as use of sunscreen (+29%), clothing (+30%), staying in the shade (+123%) or indoors (+136%) during peak sun hours, had all increased significantly (P < 0·0001). Travelling to sunny seaside holiday resorts abroad before the age of 2 years had almost doubled (P < 0·0001). The adjusted mean number of naevi per square metre body surface was significantly (P < 0·0001) lower in 2007: 6·6 [95% confidence interval (CI) 5·6–7·6], compared with 11·0 (95% CI 10·0–12·0) in 2002. Conclusions This study demonstrates increased self‐reported parental actions for sun protection of young Swedish children in recent years; in consistency, lower numbers of common melanocytic naevi were observed. Results support the use of common melanocytic naevi as an objective measure of sun exposure in children.     

The distribution pattern of segmental vitiligo: clues for somatic mosaicism

Background Segmental vitiligo is characterized by a unilateral and localized distribution. So far, the underlying mechanism is still an enigma. Objectives To get an insight into the aetiopathogenesis of segmental vitiligo by comparison with the distribution pattern of dermatoses with a possible mosaic or neurogenic background. Methods In this retrospective observational study the distribution pattern of 724 unilateral, linear or band‐shaped control lesions was compared with 181 segmental vitiligo lesions. Clinical photographs were used to score similarities according to a defined grading system (scale ranging from 0 for no similarities to 4 for complete similarity). Control lesions were evaluated both individually and after grouping into different cell types. Results In general, only a minority of cases (36·9%), showed similarities (grade 1–4) between control lesions and segmental vitiligo. Grade 2–4 similarities were seen mainly in segmental lentiginosis (73·7%, P < 0·001). The best grade for correspondence (grade 3–4) was observed significantly more only in segmental lentiginosis (36·8% vs. 3·5%, P < 0·001) and epidermal naevus verrucosus (12·5% vs. 3·7%, P = 0·008) compared with the other control lesions. The distribution pattern of segmental vitiligo significantly overlapped those of other disorders originating from melanocytes. Conclusions Our results demonstrate that the distribution pattern of segmental vitiligo is not entirely similar to any other skin disease, although some mosaic skin disorders have more overlap with segmental vitiligo than others. The remarkable clinical similarity with several cases of mosaic diseases involving melanocytes supports the hypothesis that cutaneous mosaicism may be involved in segmental vitiligo.     

Autoimmune thyroid disease in vitiligo: multivariate analysis indicates intricate pathomechanisms

Background Vitiligo/nonsegmental vitiligo (NSV) is often associated with thyroid dysimmunity although very few reports have studied this association using multivariate logistic regression. Objective To identify weighted factors associated with the presence of autoimmune thyroid disease (AITD) in a large cohort of patients with vitiligo/NSV. Methods This was a prospective observational study in 626 patients with a confirmed diagnosis of vitiligo/NSV attending the vitiligo clinic of the University Hospital Department of Dermatology, Bordeaux, France, from 1 January 2006 to 1 May 2012. The Vitiligo European Task Force (VETF) questionnaire was completed for each consecutive patient. AITD was defined as the presence of significant levels of serum antithyroperoxidase antibodies or evidence of autoimmune thyroiditis. Univariate and multivariate logistic regression procedures were conducted to identify factors associated with AITD in this cohort of patients with vitiligo/NSV. Results A total of 626 patients with vitiligo/NSV were included, of whom 131 had AITD (AITD‐vitiligo). Stress as an onset factor, familial history of AITD, body surface involvement and duration of the disease were positively associated with AITD‐vitiligo using univariate analysis, whereas female sex, age at onset of vitiligo, personal history of autoimmune disease and localization on the trunk were found to be independently associated with AITD‐vitiligo. Conclusion Vitiligo associated with AITD has clinical features distinct from vitiligo without AITD. In particular, female patients, and patients with longer duration of disease and greater body surface involvement are more likely to present with AITD and should thus be monitored for thyroid function and antithyroid antibodies on a regular basis.     

Relevance of autoimmune thyroiditis in children and adolescents with vitiligo

Background Vitiligo is the most common pigmentation‐related disorder worldwide. An autoimmune etiology is widely considered, and genetic factors may play an important role in its pathogenesis. The purpose of this study was to assess the incidence of thyroid dysfunctions and autoimmune thyroiditis in children with vitiligo and to identify related factors. Methods Fifty children with vitiligo and 50 control children were enrolled. Data on age, onset, duration, disease activity, presence of thyroid disorder, other autoimmune diseases, halo nevi, poliosis, and mucosal vitiligo were determined. Serum free triiodothyronine, free thyroxine, total T3, total T4, thyroid‐stimulating hormone, and antibodies to thyroperoxidase and thyroglobulin were measured. Thyroid gland efficiency was evaluated. Results The mean age at onset of vitiligo was 7.26 ± 4.43 years. The duration of vitiligo was 2.26 ± 2.95 years. Vulgaris‐type vitiligo was the most common form in our patients (56%), and 42% reported at least one family member with thyroid disorder, autoimmune disease, or both. Overt hypothyroidism or hyperthyroidism were not detected. We found a significant association between autoimmune thyroiditis and both sex and disease duration (P = 0.046 and P = 0.07, respectively), but no association between autoimmune thyroiditis and age, age at onset of vitiligo, halo nevi, poliosis, mucosal involvement, disease activity, or family history of vitiligo, autoimmunity, or thyroid disorders. Conclusions Children with vitiligo show an increased incidence of autoimmune thyroiditis. Children with vitiligo, especially girls and subjects with generalized/vulgaris‐type vitiligo, should be screened annually for thyroid function and antithyroid antibodies to assist in the early diagnosis and therapy of autoimmune thyroiditis.     

Involvement of T cells in early evolving segmental vitiligo

Recent studies have suggested an overlapping autoimmune mechanism between segmental vitiligo (SV) and nonsegmental vitiligo (NSV). Although T‐cell infiltration is observed in the margins of active lesions in NSV, the histopathological characteristics of the active margin of SV are not well known. To determine if T‐cell inflammatory responses are present in the active margin of SV lesions, biopsies were taken from the active margin of a lesion in 12 patients with early or actively spreading SV and compared with a normal control sample (on the symmetrical, opposite site of the same dermatome). The samples were stained for CD4, CD8, CD25 and interferon‐γ. Lymphocytic infiltration was seen in 70% of patients. CD4+ T cells infiltrated the dermis, while CD8+ T cells were present in the epidermis or attached to the basal layer. The increase in the number of CD8+ T cells was significant (P < 0.04), while CD4+ or CD25+ T cells also appeared to be increased in number, but this was not significant. These results suggest that SV also has an autoimmune mechanism in the early evolving stage.     

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.     

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.     

Impact of glucocorticoid‐induced adverse events on adherence in patients receiving long‐term systemic glucocorticoid therapy

Summary Background Factors influencing adherence to long‐term (i.e. ≥ 3 months) systemic glucocorticoid therapy are poorly understood. Objective To evaluate the relationship between glucocorticoid‐induced adverse events and therapeutic adherence in patients on long‐term glucocorticoid treatment. Methods A cross‐sectional survey was conducted in three departments of dermatology/internal medicine between April and September 2008. Patients were asked to provide data regarding symptoms they attributed to glucocorticoids, and adherence to treatment was measured using the four‐item Morisky–Green adherence scale. Logistic regression analyses were used to assess the association between reported adverse events and adherence to glucocorticoids. Results A total of 255 questionnaires were completed and analysed [women 78%; median age 48 years (interquartile range (IQR) 34–65); connective tissue diseases 59%; median duration of treatment 24 months (IQR 8–72); median daily dose 10 mg (IQR 6–20)]. Among these 255 patients, 199 (78%) reported themselves as ‘good adherents’ and 56 (22%) as ‘poor adherents’ to treatment. Poor adherence was associated with younger age [odds ratio (OR) 0·97, 95% confidence interval (CI) 0·95–0·99, per increasing year; P < 0·01], presence of glucocorticoid‐induced epigastralgia (OR 4·02, 95% CI 2·00–8·09; P < 0·01) and presence of glucocorticoid‐induced morphological changes (OR 2·49, 95% CI 1·19–5·21; P = 0·02). Moreover, patients with poor adherence were likely to report concomitantly poor adherence to dietary advice associated with glucocorticoid therapy (OR 2·44, 95% CI 1·12–5·26; P = 0·02). Conclusions As with other chronic therapies, the presence of glucocorticoid‐induced adverse events is associated with an altered self‐reported adherence to glucocorticoids. Patients who report epigastric pain or morphological changes that they associate with glucocorticoid therapy are particularly at risk of poor adherence. Adherence to dietary advice associated with glucocorticoid therapy may be an indirect measure of treatment adherence.     

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.     

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.