ArticleLiterature Review

Current Management of Pediatric Vitiligo

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Abstract

Vitiligo is a common inflammatory disorder with worldwide prevalence of 0.4–2 % of the population, with half of cases beginning in childhood. The management of childhood vitiligo should be tailored to avoid negative effects on the overall growth and psychological development of the patient. Therapy of vitiligo in childhood is chosen based on the location of the lesions, lesion age, and extent of lesions in the context of the child’s age and the developmental status of the child. There are four age categories in childhood vitiligo: [1] infantile and toddler (rare) (ages 0–3 years), [2] ages 4–8 years, [3] ages 9–12 years, and [4] 13+ years of age, based on developmental stage, psychological maturation, and ability to comply or participate in therapy. These categories are also differentiated psychologically by susceptibility to bullying, self-image development, and personal concern with lesion appearance, which increases with time. Intervention is advisable in cases with facial and leg involvement due to prominence of lesions and cosmetic defect. Medical interventions are largely the usage of topical therapies including corticosteroids and calcineurin inhibitors, some vitamin therapy (oral and topical vitamin D), and judicious introduction of phototherapy sources based on age and severity. Screening and appropriate subspecialist referral for co-morbidities (e.g., thyroid disease, celiac disease, psychological distress, and vitamin D deficiency) may enhance overall health. Cosmesis and camouflage are generally safe in childhood and have been noted to improve overall quality of life in this grouping. Genetic transmission of vitiligo is minimal at 5–6 % in first-degree relatives. This article reviews the therapeutics of pediatric vitiligo from the perspective of developmental stages and response to therapy.

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... Local side effects of cream steroids include atrophy, striae, telangiectases, perioral dermatitis, and glaucoma (when used around the eyes). [6] When choosing a cream corticosteroid, the site of the lesion and age of the patient need to be taken into consideration. Potent corticosteroids can be used for treating lesions on the body, whereas topical corticosteroids with less potency should be selected for the face, neck, and intertriginous regions and lesions in children. ...
... Avoidance of application over atypical pigmented lesions is recommended. [6] Two times daily use is required for effective results. Topical calcineurin inhibitors are deemed to be the first-line therapy for facial vitiligo of childhood by the Vitiligo European Task Force. ...
... Topical calcineurin inhibitors are deemed to be the first-line therapy for facial vitiligo of childhood by the Vitiligo European Task Force. [6] Topical Vitamin D Calcipotriene is a Vitamin D analogous that is not effective for vitiligo individually, but is assistant helpful when taken with creams corticosteroids (e.g., betamethasone) for facial and body vitiligo in childhood or NB-UVB. [6] Phototherapy is a beneficial therapeutic option for widespread vitiligo, especially in pediatric patients. ...
... A abordagem do vitiligo infantil é um desafio, pois a doença tem consequências psicológicas importantes. 1,19 O uso de inibidores tópicos de calcineurina para a cabeça e o pescoço, corticosteróides tópicos para o tronco e membros e fototerapia com UVB de banda estreita para doença extensa são as abordagens de primeira linha na terapêutica do vitiligo. 19 A PUVAterapia era classicamente a fototerapia de referência no vitiligo, mas tem sido substituída pela fototerapia com UVB-BE, por não ter tantos efeitos adversos, sendo mais fácil para a criança, por não exigir proteção ocular depois da sessão. ...
... 1,19 O uso de inibidores tópicos de calcineurina para a cabeça e o pescoço, corticosteróides tópicos para o tronco e membros e fototerapia com UVB de banda estreita para doença extensa são as abordagens de primeira linha na terapêutica do vitiligo. 19 A PUVAterapia era classicamente a fototerapia de referência no vitiligo, mas tem sido substituída pela fototerapia com UVB-BE, por não ter tantos efeitos adversos, sendo mais fácil para a criança, por não exigir proteção ocular depois da sessão. 1,[19][20][21][22] O primeiro objetivo da fototerapia é estabilizar a doença, conseguido em 80%-85% dos casos de doença generalizada, com 2 sessões semanais de UVB-BE. ...
... 19 A PUVAterapia era classicamente a fototerapia de referência no vitiligo, mas tem sido substituída pela fototerapia com UVB-BE, por não ter tantos efeitos adversos, sendo mais fácil para a criança, por não exigir proteção ocular depois da sessão. 1,[19][20][21][22] O primeiro objetivo da fototerapia é estabilizar a doença, conseguido em 80%-85% dos casos de doença generalizada, com 2 sessões semanais de UVB-BE. 19 A repigmentação é o objetivo secundário, alcançado segundo vários estudos entre 37% a 75% dos casos, com efeitos adversos ligeiros. ...
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Atualmente, com o desenvolvimento recente de agentes biológicos e outros novos fármacos, alguns dos quais com o seu uso já aprovado em idade pediátrica, torna-se importante contextualizar o papel da fototerapia na dermatologia. Esta tem um perfil de segurança excelente e bem reconhecido desde há décadas, para além de não necessitar de monitorização laboratorial, o que constitui uma mais valia, sobretudo na população pediátrica. Tem sido utilizada com sucesso nesta faixa etária no tratamento de diversas doenças dermatológicas. Neste artigo é realizada uma revisão acerca das principais particularidades da utilização da fototerapia em idade pediátrica, focando os efeitos adversos, os principais obstáculos, as suas indicações e a seleção individualizada das diferentes modalidades, de modo a facilitar a prática clínica desta terapêutica.
... Topical vitamin D analogues are thought to have an impact by making an immunomodulation and melanogenesis stimulation through vitamin D receptors (34)(35)(36)(37). A study on the subject has reported success in 10 cases out of 18 children (31). ...
... Selection of treatment is based on the child's age, lesion localization, prevalence and family preference. It has impact on success in clinic type (34). Various treatment guides are being discussed (34)(35)(36)(37)(38). ...
... It has impact on success in clinic type (34). Various treatment guides are being discussed (34)(35)(36)(37)(38). With regards to vitiligo treatment, systemic, topical treatments (containing topical corticosteroid, topical vitamin D analogues and topical calcineurin inhibitors), phototherapy (narrow band UVB, PUVA, microphototherapy), depigmenting agents, surgical intervention are among the options (34)(35)(36)(37). ...
... 1. Topical corticosteroids: Topical steroids are the first-line treatment for body lesions, barring intertriginous and genital areas, and have the best response over sun-exposed sites and in newer lesions [66,67]. Preceding laser dermabrasion and combination with NBUVB are found to increase the treatment efficacy in refractory vitiligo [68]. ...
... inhibition of T-cell activation, the role of tacrolimus in inducing melanocyte migration and differentiation has been described recently [70]. Vitiligo European Task Force considers it as the first-line treatment for facial vitiligo, unlike its use as second-line agent in atopic dermatitis [66,67]. Twice-daily application ensures optimal results [71]. ...
... Twice-daily application ensures optimal results [71]. Occlusion, preceding microdermabrasion, sunlight and adjuvant NB-UVB or 308-nm laser have all been reported to augment therapeutic response to topical calcineurin inhibitors [66]. Black-box warning by FDA of potential risk of carcinoma and lymphoma warrants avoidance of tacrolimus use in children less than the age of 2 years. ...
Chapter
Vitiligo is a common pigmentary disorder characterised by the loss of functioning melanocytes from the basal layer of epidermis, leaving behind depigmented patches on the skin. It has a complex aetiopathology. Even though there are various theories describing the pathomechanisms of melanocyte loss, the initial trigger for melanocyte directed attack and the final steps causing melanocyte destruction is still speculative. The poor understanding of a common pathway causing melanocyte loss reflects in the lack of a targeted therapy in the medical management of vitiligo in this era of biologicals. The unravelling of interferon (IFN)-γ/CXCL10 axis in the causation of melanocyte directed attack and the observation of clinical usefulness of tofacitinib, which blocks the same pathway, give new hope in the direction of targeted therapy in vitiligo. In vitiligo, unlike psoriasis, the physician needs to address not only the issue of halting the inflammatory cascade causing the overt manifestation of the disease but also that of reviving the lost melanocytes, to regain normal skin colour. This chapter discusses the recent advances in the understanding of vitiligo pathogenesis and includes an update on the conventional and newer modalities in the medical management of vitiligo. A brief overview of the approach to the medical management of vitiligo is given at the end of the chapter.
... So far, several theories have been formulated that try to explain the etiopathogenesis of this dermatosis, including: -Autoimmune theory: this suggests that the destruction of melanocytes is due to an immune disorder. This is confirmed by studies indicating more frequent comorbidity vitiligo with other autoimmune diseases, including Addison's disease, inflammation the choroid of the eye, retinitis, Hashimoto's disease, type I diabetes or psoriasis [4]. This theory is also supported by the more frequent occurrence of antibodies to melanocytes, as well as the presence of a cellular immune response mediated by lymphocytes T CD 8+, which may induce the destruction of melanocytes [5]. ...
... The mentioned phenomenon it occurs even in 20-60% of patients with vitiligo [1]. Due to frequent stigmatization children suffering from vitiligo, especially among their peers, to the clinical picture the occurrence of depression and other mood disorders should also be added [4]. Albinism has an unpredictable course of the disease: it can last for a long time years, and to be rapidly progressive. ...
Article
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Vitiligo is a chronic skin condition which affects 0,5-2% of the world’s population, without any sex or ethnical predilection. Clinically it is characterized by the development of well-defined depigmented macules. Although its etiopathogenesis is exquisitely compound and remains not fully anderstood, it is known that it results from the destruction of melanocytes present in the skin. The aim of this paper is to present vitiligo clinical picture in a children population, its etiopathogenesis and available therapeutical methods. There are many therapeutic options for vitiligo, none of which is fully effective, hence appropriate patients education concerning various medical and cosmetic therapies, as well as the psychological aspects of the disease, is extremely important.
... 24 Prevalensi vitiligo berkisar antara 0,4-2% populasi dunia, dengan separuh kasus dimulai pada usia anak. 25 Efek samping yang ditimbulkan oleh NB-UVB pada vitiligo adalah eritema, pruritus, dan xerosis. Risiko terjadinya melanoma dan dan keganasan kulit pada pasien vitiligo dilaporkan rendah. ...
Article
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Phototherapy is a non-ionizing ultraviolet (UV) radiation therapy used as a treatment for several medical conditions. The mechanism of action of phototherapy is to act as antiproliferative, induce apoptotic, and provide immunosuppressive effect. Several therapeutic modalities that can be used as alternative therapy in children include NB-UVB, BB-UVB, ultraviolet A, PUVA, and excimer laser. Phototherapy in children is indicated especially in diseases such as psoriasis, atopic dermatitis, vitiligo, pityriasis lichenoides, and mycoses fungoides. The use of phototherapy has indications, contraindications, dose, and side effects that should be considered when choosing appropriate phototherapy in children. Common side effects are erythema, xerosis, burning sensation, and itching. Several groups of patients with refractory complaints are advised to use additional phototherapy modalities, either as monotherapy or in combination with topical and systemic therapy.
... In vitiligo, topical corticosteroids are the first-line treatment in the extra-facial areas (barring intertriginous and genital sites) [153]. Pulse therapy (2 consecutive days/week) with betamethasone 0.1 mg/kg for 3 months, followed by tapering of the dose by 1 mg every month over the following 3months, is a possible therapeutic option in cases of progressive generalized disease [154]. ...
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Corticosteroids are the mainstay of therapy for many pediatric disorders and sometimes are life-saving. Both endogenous and synthetic derivatives diffuse across the cell membrane and, by binding to their cognate glucocorticoid receptor, modulate a variety of physiological functions, such as glucose metabolism, immune homeostasis, organ development, and the endocrine system. However, despite their proved and known efficacy, corticosteroids show a lot of side effects, among which growth retardation is of particular concern and specific for pediatric age. The aim of this review is to discuss the mechanism of action of corticosteroids, and how their genomic effects have both beneficial and adverse consequences. We will focus on the use of corticosteroids in different pediatric subspecialties and most common diseases, analyzing the most recent evidence.
... It leads to emotional distress, low self-esteem [4] and affects sexual life of the patients [5]. Often the affected persons, especially the children, get bullied and stigmatized [6]. This disease, also known as leukoderma is pervasive across all races, though instances are higher in some [7]. ...
Article
Vitiligo is an idiopathic systemic autoimmune disease affecting skin, hair and oral mucosa. This genetic yet acquired disease characterized by melanin loss is a cause of morbidity across all races. Though thyroid disturbance has been recognized as a key trigger of this pathology, an array of other factors plays critical role in its manifestation. Multiple hormones (corticotropin-releasing hormone, adrenocorticotropic hormone, α-melanocyte-stimulating hormone, melatonin, calcitriol, testosterone, estrogen), genes (Human leukocyte antigen (HLA), Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), Forkhead box D3 (FOXD3), Cluster of differentiation 117 (CD117), Estrogen receptor (ESR) 1, Cyclooxygenase-2 (COX2), Vitiligo-associated protein 1 (VIT1)), and lifestyle choices (stress, diet, cosmetic products, and medications) have been suspected as drivers of this disorder. The pathological mechanisms have been understood in recent times, with the aid of genomic studies; however a universally-effective therapy is yet to be achieved. This review discusses these under-investigated facets of vitiligo onset and progression; hence, it is expected to enrich vitiligo research.
Article
Vitiligo is a common disorder; however, its management is unknown by many primary-care doctors and pediatricians. Most articles focus on adults; we analyze the characteristics and impact on children. A single-center retrospective study was conducted over 10 years on 254 children diagnosed with vitiligo. About 50.4% were male with a mean age of 8.24 years. There was a slight predominance of nonsegmented vitiligo. About 12.59% had family history of vitiligo and 11.4% of autoimmune diseases. Around 15.7% patients presented other dermatological diseases and 9.05%, autoimmune diseases. No significant statistical differences were found when comparing age, sex, and type of vitiligo with other variables. Almost 96.06% received treatment with calcineurin inhibitors and 66.53% topical steroids. Around 77% obtained repigmentation, and out of the initial nonresponders, 16% responded to phototherapy. In general, our results concur with the scarce literature. A long-term follow-up of children with vitiligo is needed to identify treatment side effects and diseases associated.
Article
Background: Vitiligo has a negative effect on children's physical and psychological health. Few studies have examined long-term treatment efficacy for childhood vitiligo. Therefore, we evaluated the long-term effectiveness of non-surgical combination therapy in pediatric patients with vitiligo and analyzed factors that affect its efficacy. Methods: Pediatric patients (⩽12 years) with vitiligo who were treated with topical corticosteroids/topical calcineurin inhibitors and phototherapy for 12 months were retrospectively studied. Short-term systemic corticosteroids were administered according to individual clinical conditions. All lesions were photographed to assess repigmentation at 3-month intervals. Clinical data, the treatment effectiveness, and factors affecting the therapeutic effect were analyzed. Results: Overall, 110 children (51 [53.6%] girls; mean [SD] age, 7.1 ± 3.0 years; 104 [94.5%] with activity status) were treated for a mean period of 23.13 ± 14.03 months (range, 5-86 months). The overall >50% repigmentation rate was 64.5%. A longer duration of treatment was associated with a higher repigmentation rate (X2 trend = 36.229, P < .001). The vitiligo disease activity score at the first visit was positively correlated with the overall repigmentation rate (rs = 0.301, P = .001). Conclusions: Treatment lasting longer than 1 year is recommended in children with vitiligo. The best repigmentation effect can be achieved by combination therapy in the rapid progression stage.
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Photodermatology
Chapter
In dermatitis herpetiformis direct immunofluorescent examination shows granular deposition of IgA antibody in dermal papilla
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One-third to one-half of vitiligo incidence is in pediatric population
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Vitiligo commonly affects children, with half of affected individuals experiencing disease onset before the age of 20. Because childhood is a time of advancement in social and psychological development, understanding the extent of the effect of the disease and means of alleviation is crucial. Vitiligo has been shown to decrease children's quality of life, with greater distress in children with highly visible lesions and darker skin tones. This article reviews the literature regarding interventions that have been analyzed in children. Studies evaluating the effect of camouflage, cognitive behavioral therapy, psychological self‐help tools, and support groups on the psychosocial aspects of vitiligo were included. The review highlights the ongoing need for studies to better understand the modalities described in this article, as well as others, such as skin dyes, bleaching creams, medical tattooing; week‐long camps that cater to children with chronic skin disease; and biofeedback, that might have a role in preventing the psychosocial sequelae of childhood vitiligo.
Article
Background Tacrolimus is a conventional medication for the treatment of vitiligo, but the effect of a single medication is limited. Objective This paper aims at observing the effects, adverse responses, and repigmentation results of the joint treatment of vitiligo by Carbon dioxide (CO2) fractional laser together with tacrolimus. Methods Forty‐five patients with vitiligo were randomly divided into two groups: treatment (T) group and control (C) group, and each group was further divided into three subgroups (face, torso and limbs, and hand and foot) according to the location of the skin defect. Both groups used topical 0.1% tacrolimus cream, but the T group was given one CO2 fractional laser treatment each month. We observed the clinical efficacy, adverse responses, and repigmentation results after 6 months. Results Compared to the C group, the T group showed better improvement in both objective and subjective assessments. When the treatment time was increased, the efficacy was also improved, and the repigmentation in the T group occured in three ways: perifollicular repigmentation, marginal repigmentation and diffuse repigmentation. There were three cases of isomorphic responses (2 cases in the rapid progression stage, one case in the progression stage), and 1 case formed scarring on the neck in the T group. Conclusions The treatment of vitiligo by CO2 fractional laser together with tacrolimus is significantly effective and is most suitable for patients in the progression stage. Patients in the rapid progression stage should use this approach with caution, and its efficacy was limited for patients in the stable stage. An extended course of treatment is helpful for the repigmentation of white patches. All three forms of repigmentation can occur in the joint treatment of vitiligo by CO2 fractional laser together with tacrolimus. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.
Chapter
This chapter presents the various issues encountered when treating pediatric and pregnant patients with vitiligo, based on available data. Psychosocial issues extend beyond childhood, and therefore special care must be taken to offer treatment, guidance, information, and access to support groups for children suffering from vitiligo, and also their caretakers. Pregnancy is a known trigger for vitiligo disease onset, but not all women with pre-existing disease experience exacerbation during pregnancy. Vitiligo is a multifactorial genetic disorder with complex genetic and environmental interactions. Many drugs and therapies used for the treatment of vitiligo are unsafe or not well-studied in pregnancy, and the physician should take care to carefully weigh the risks and benefits of specific treatment regimens for this disease in the gravid patient. Reassurance as to the benign effect of vitiligo on the fetus and low rates of vitiligo transmission can be given to the pregnant vitiligo patient.
Article
Background: Phototherapy especially narrow-band UV-B (NBUVB) has been considered as mainstay of therapy in nonsegmental vitiligo (generalized type). Topical tacalcitol has also been claimed to be effective, either as monotherapy or as combination therapy. Purpose: Comparison of clinical efficacy and safety of NBUVB in combination with topical tacalcitol vs. NBUVB alone in vitiligo. Material & methods: Thirty patients with symmetrical vitiliginous lesions were enrolled for 24 weeks. Patients were instructed to apply tacalcitol ointment on right side of body once daily. In addition, the whole body was irradiated with NBUVB thrice weekly. All the patients were examined, and lesional photography was done. Patients were also followed up for 6 months post-treatment. Results: Our study resulted in two key findings: (1) There was a statistically significant difference in mean percentage of repigmentation at 8, 16 and 24 weeks between combination therapy and NBUVB. (2) The mean cumulative dose and number of treatment sessions for initial repigmentation were significantly lower with combination therapy. No serious adverse effects were observed during the study period. Conclusion: Topical tacalcitol potentiates efficacy of NBUVB as it enhances extent of pigmentation, decrease time to repigmentation and lowers the cumulative doses of NBUVB, thereby leading to greater patient satisfaction and improved compliance.
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Topical calcineurin inhibitors (TCIs), commercially available since 2000-2001, are the first and only topical medications approved for chronic treatment of atopic dermatitis (AD) in pediatric patients and remain a welcomed alternative to topical corticosteroids. In January 2006, the US Food and Drug Administration (FDA) issued a boxed warning requirement based on a theoretical risk of malignancy (including lymphoma) with TCI use. However, in the years since, analyses of epidemiologic and clinical data have failed to demonstrate a causal relationship between TCI use and malignancy or lymphoma risk, especially for pimecrolimus cream. In fact, the observed number of malignancies and lymphomas observed both in post-marketing surveillance and reported to the FDA using its adverse events reporting system is much lower among TCI-exposed patients than the expected number for the general population. Furthermore, among children enrolled in post-marketing pediatric registry studies for both tacrolimus and pimecrolimus followed for up to 5.5 years [10,724 patient-years (PY)] or 6.5 years (16,219 PY), respectively, the observed number of malignancies and lymphomas is very low and similar to the number expected for a sample of similar size in the general population. In addition to reporting these comparative malignancy and lymphoma data, this article provides a historical overview of the boxed warning requirement and critically evaluates the preclinical, clinical, and epidemiological evidence that has thus far failed to substantiate a relationship between TCI use and malignancy. The authors also provide practical clinical advice for optimizing AD management and patient care in the context of the boxed warning.
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Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse gestational outcomes. To examine whether supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2011), the International Clinical Trials Registry Platform (ICTRP) (31 October 2011), the Networked Digital Library of Theses and Dissertations (28 October 2011) and also contacted relevant organisations (8 April 2011). Randomised and quasi-randomised trials with randomisation at either individual or cluster level, evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy. Two review authors independently i) assessed the eligibility of studies against the inclusion criteria ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Data were checked for accuracy. The search strategy identified 34 potentially eligible references. We included six trials assessing a total of 1023 women, excluded eight studies, and 10 studies are still ongoing. Five trials involving 623 women compared the effects of vitamin D alone versus no supplementation/placebo and one trial with 400 women compared the effects of vitamin D and calcium versus no supplementation.Only one trial with 400 women reported on pre-eclampsia: women who received 1200 IU vitamin D along with 375 mg of elemental calcium per day were as likely to develop pre-eclampsia as women who received no supplementation (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.33 to 1.35). Data from four trials involving 414 women consistently show that women who received vitamin D supplements had higher concentrations of vitamin D in serum at term than those women who received no intervention or a placebo; however the magnitude of the response was highly heterogenous. Data from three trials involving 463 women suggest that women who receive vitamin D supplements during pregnancy less frequently had a baby with a birthweight below 2500 grams than those women receiving no treatment or placebo; statistical significance was borderline (RR 0.48; 95% CI 0.23 to 1.01).In terms of other conditions, there were no significant differences in adverse side effects including nephritic syndrome (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women); stillbirths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) or neonatal deaths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) between women who received vitamin D supplements in comparison with women who received no treatment or placebo. No studies reported on preterm birth, maternal death, admission to neonatal intensive care unit/special nursery or Apgar scores. Vitamin D supplementation in a single or continued dose during pregnancy increases serum vitamin D concentrations as measured by 25-hydroxyvitamin D at term. The clinical significance of this finding and the potential use of this intervention as a part of routine antenatal care are yet to be determined as the number of high quality trials and outcomes reported is too limited to draw conclusions on its usefulness and safety. Further rigorous randomised trials are required to evaluate the role of vitamin D supplementation in pregnancy.
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Vitiligo is the most prevalent pigmentary disorder which occurs worldwide, with an incidence rate between 0.1-4 percent. It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of vitiligo. The purposes of this study were evaluating the efficacy of supplemental zinc on the treatment of vitiligo. This randomized clinical trial was conducted for a period of one year. Thirty five patients among 86 participants were eligible to entrance to the study. The patients in two equal randomized groups took topical corticosteroid and combination of oral zinc sulfate-topical corticosteroid. The mean of responses in the corticosteroid group and the zinc sulfate-corticosteroid combination group were 21.43% and 24.7%, respectively. Although, the response to corticosteroid plus zinc sulfate was more than corticosteroid, there was no statistically significant difference between them. It appeared that more robust long-term randomized controlled trials on more patients, maybe with higher doses of zinc sulfate, are needed to fully establish the efficacy of oral zinc in management of vitiligo. chiCTRTRC10000930.
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Vitiligo is a common hypopigmentation disorder with significant psychological impact if occurring before adulthood. A pilot clinical trial to determine the feasibility of an RCT was conducted and is reported here. 12 participants 12 to 35 years old were recruited to a prospective open-label pilot trial and treated with 60 mg of standardized G. biloba two times per day for 12 weeks. The criteria for feasibility included successful recruitment, 75% or greater retention, effectiveness and lack of serious adverse reactions. Effectiveness was assessed using the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF), which are validated outcome measures evaluating the area and intensity of depigmentation of vitiligo lesions. Other outcomes included photographs and adverse reactions. Safety was assessed by serum coagulation factors (platelets, PTT, INR) at baseline and week 12. After 2 months of recruitment, the eligible upper age limit was raised from 18 to 35 years of age in order to facilitate recruitment of the required sample size. Eleven participants completed the trial with 85% or greater adherence to the protocol. The total VASI score improved by 0.5 (P = 0.021) from 5.0 to 4.5, range of scale 0 (no depigmentation) to 100 (completely depigmented). The progression of vitiligo stopped in all participants; the total VASI indicated an average repigmentation of vitiligo lesions of 15%. VETF total vitiligo lesion area decreased 0.4% (P = 0.102) from 5.9 to 5.6 from baseline to week 12. VETF staging score improved by 0.7 (P = 0.101) from 6.6 to 5.8, and the VETF spreading score improved by 3.9 (P < 0.001)) from 2.7 to -1.2. There were no statistically significant changes in platelet count, PTT, or INR. The criteria for feasibility were met after increasing the maximum age limit of the successful recruitment criterion; participant retention, safety and effectiveness criteria were also met. Ingestion of 60 mg of Ginkgo biloba BID was associated with a significant improvement in total VASI vitiligo measures and VETF spread, and a trend towards improvement on VETF measures of vitiligo lesion area and staging. Larger, randomized double-blind clinical studies are warranted and appear feasible. Clinical trials.gov registration number NCT00907062.
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Primary headaches (migraines and tension-types headaches) are very common in school-aged children. Ginkgolide B, a herbal constituent extract from Ginkgo biloba tree leaves, was considered as a promising pharmacological aid for the treatment of migraine in adult patients because of its modulation of the glutamatergic transmission in the CNS and on antiplatelet activating factor (PAF). The aim of study is to verify the effectiveness and safety of association of Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium complex for brief prophylaxis in a population of school-aged children with migraine. In our sample after 3 months of treatment with association of Ginkgolide B/Coenzyme Q10/Riboflavin/Magnesium complex, the mean frequency per month of migraine was significantly decreased (9.71 ± 4.33 vs. 4.53 ± 3.96 attacks; p < 0.001). Our findings suggest that in childhood headache management, the use of alternative treatments must be considered not to evoke a placebo effect, but as soft therapy without adverse reactions.
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Generalized vitiligo is an autoimmune disease of skin pigmentation that is associated with increased prevalence of other autoimmune diseases, particularly autoimmune thyroid disease (AITD; principally Hashimoto's disease and Graves' disease), both in vitiligo patients and their close relatives, suggesting a heritable predisposition involving, in part, shared susceptibility genes. This review summarizes current knowledge of vitiligo epidemiology and genetics, highlighting recent findings from genome-wide approaches to disease gene identification, emphasizing susceptibility loci shared with other autoimmune diseases, particularly AITD, as well as some important differences. Inherited susceptibility to generalized vitiligo involves a number of specific genes, many of which are shared with other autoimmune diseases that are epidemiologically associated with vitiligo, including AITD, confirming a longstanding hypothesis about the genetic basis of these disorders. These genes provide potential therapeutic targets for novel approaches to treatment as well as for approaches to presymptomatic diagnosis and disease prevention in individuals with inherited susceptibility to this group of autoimmune diseases.
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A black box warning describes a potential risk of malignancy associated with topical use of pimecrolimus to treat atopic dermatitis due to its similarity to oral calcineurin inhibitors used in solid-organ transplantation and spontaneous reporting of malignancies, including lymphomas and cutaneous malignancies. To evaluate the risk of malignancy in a postmarketing study of children exposed to pimecrolimus. A longitudinal cohort study among a nationwide ongoing long-term cohort of children enrolled in the Pediatric Eczema Elective Registry (PEER) who had a history of atopic dermatitis and pimecrolimus use with data available up through May 2014. Reports of malignancy among those in the PEER compared with expected rates from the Surveillance, Epidemiology, and End Results (SEER) program. Overall, 7457 children were enrolled in the PEER, for a total of 26 792 person-years. Children used a mean (SD) of 793 (1356) g of pimecrolimus when enrolled in the study. As of May 2014, five malignancies had been reported. These include 2 leukemias, 1 osteosarcoma, and 2 lymphomas. No skin cancers were reported. The standardized incidence ratio for all malignancies (primary outcome) based on the age-standardized SEER population was 1.2 (95% CI, 0.5-2.8). As secondary analyses, the standardized incidence ratios (based on 2 cases for each) were 2.9 (95% CI, 0.7-11.7) for lymphoma and 2.0 (95% CI, 0.5-8.2) for leukemia. None of these findings were statistically significant. Based on more than 25 000 person-years of follow-up, it seems unlikely that topical pimecrolimus as it was used in the PEER cohort to treat atopic dermatitis is associated with an increased risk of malignancy.
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Vitiligo is a common condition seen in a dermatology office, which has a variety of comorbidities. Worldwide, the prevalence of vitiligo ranges from 0.4 to 2.0 %, with regions of greater or lesser prevalence. Most studies demonstrate slightly greater prevalence in females and 50 % onset in childhood, but exceptions to these rules exist. Childhood vitiligo has been associated with atopic diathesis, halo nevi, and family history of vitiligo and autoimmunity. Post-pubescent vitiligo has been associated with greater acrofacial disease and thyroid disease, and early data supports reduced non-melanoma and melanoma skin cancer risk. Disease severity is inversely proportional to distance from the equator, and birthplace outside the USA may be somewhat protective against severe disease. This article reviews the epidemiology of vitiligo and the epidemiologic relationship of vitiligo to comorbid diseases and family history, with a focus on recent literature.
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Celiac disease (CD) is a lifelong gluten-sensitive intestinal enteropathy that is multifactorial in its etiology. In the present study, we evaluated basic anthropometric, clinical, laboratory, and histological features of 140 Turkish children with CD. We particularly underscored the association of CD with other autoimmune diseases. During the period from 1999 to 2005, CD was diagnosed in 140 children according to ESPGAN criteria. The age, gender, clinical findings, hematological, and biochemical parameters at diagnosis were noted. Symptoms and signs were recorded. Endoscopic intestinal biopsies were taken from all children. Of the 140 children with CD, 75 (53.6%) were female, and 65 (46.4%) were male. Mean age was 8.56 ± 4.43 years (range 13 months to 18 years). The most frequent symptom was failure to thrive (81.4%), followed by chronic diarrhea (60%). Of the children with CD, nine (6.4%) had type 1 diabetes mellitus (DM), six (4.3%) had familial Mediterranean fever, three (2.1%) had alopecia areata, three (2.1%) had vitiligo, three (2.1%) had Down syndrome, two (1.4%) had lung tuberculosis, two (1.4 %) had autoimmune hepatitis, two (1.4%) had growth hormone deficiency, one (0.7%) had osteogenesis imperfecta, and one (0.7%) had Floating Harbor Syndrome. Elevated serum levels of ALT, CK and AST were detected in 48(34.8%), 50 (38.2%) and 67 (48.6%) children, respectively. The spectrum of clinical findings is very wide. In order to avoid overlooking CD in patients with extra intestinal symptoms and signs, physicians, especially pediatricians, should be informed about new atypical manifestations of CD.
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Background: Genetic findings suggesting a lower susceptibility to melanoma in patients with vitiligo are supported by recent clinical studies. Nonmelanoma skin cancer (NMSC) has also been studied, but mainly in small samples, and with conflicting results. Objective: We sought to study the relative risk (RR) of melanoma and NMSC in patients with vitiligo compared with that in patients seen for vascular surgery. Methods: The frequency of melanoma and NMSC was compared between patients with vitiligo and patients seen for vascular surgery. Occurrence of skin cancer was compared by computing RR and modeled using multiple logistic regression. Results: Overall, the crude RR for melanoma was 0.24 (95% confidence interval [CI] 0.13-0.45) in patients with vitiligo compared with those with a nondermatologic condition (occurrence 1.1‰, 95% CI 0.5‰-2.0‰ in patients with vitiligo and occurrence 4.5‰, 95% CI 3.8‰-5.4‰ in the control cohort). The crude RR for NMSC was 0.19 (95% CI 0.14-0.17) and the occurrence was 3.8‰ (95% CI 2.7‰-5.2‰) among patients with vitiligo and 19.6‰ (95% CI 18.0‰-21.4‰) in control subjects. Patients with vitiligo who underwent phototherapy had a markedly higher risk of both cancers. Conclusions: In our large study, patients with vitiligo have a decreased risk of developing skin neoplasms, even considering that a larger proportion in this patient group is exposed to higher levels of ultraviolet radiation.
Article
Importance Narrowband UV-B (NB–UV-B) phototherapy is used extensively to treat vitiligo. Afamelanotide, an analogue of α–melanocyte-stimulating hormone, is known to induce tanning of the skin.Objective To evaluate the efficacy and safety of combination therapy for generalized vitiligo consisting of afamelanotide implant and NB–UV-B phototherapy.Design, Setting, and Participants This study was performed in 2 academic outpatient dermatology centers and 1 private dermatology practice. We enrolled men and women 18 years or older with Fitzpatrick skin phototypes (SPTs) III to VI and a confirmed diagnosis of nonsegmental vitiligo that involved 15% to 50% of total body surface area. Vitiligo was stable or slowly progressive for 3 months. Patients were randomized to combination therapy (n = 28) vs NB–UV-B monotherapy (n = 27). After 1 month of NB–UV-B phototherapy, 16 mg of afamelanotide was administered subcutaneously to the combination therapy group monthly for 4 months while NB–UV-B phototherapy continued; the other group continued to receive NB–UV-B monotherapy.Interventions Narrowband UV-B monotherapy vs combined NB–UV-B phototherapy and afamelanotide.Main Outcomes and Measures Response on the Vitiligo Area Scoring Index and Vitiligo European Task Force scoring system.Results Response in the combination therapy group was superior to that in the NB–UV-B monotherapy group (P < .05) at day 56. For the face and upper extremities, a significantly higher percentage of patients in the combination therapy group achieved repigmentation, and at earlier times (face, 41.0 vs 61.0 days [P = .001]; upper extremities, 46.0 vs 69.0 days [P = .003]). In the combination therapy group, repigmentation was 48.64% (95% CI, 39.49%-57.80%) at day 168 vs 33.26% (95% CI, 24.18%-42.33%) in the NB–UV-B monotherapy group. Notable adverse events included erythema in both groups and minor infections and nausea in the combination therapy group. Comparison between Fitzpatrick SPTs showed patients with SPTs IV to VI in the combination therapy group had improvement in the Vitiligo Area Scoring Index at days 56 and 84 (P < .05); no significant difference was noted in patients with SPT III.Conclusions and Relevance A combination of afamelanotide implant and NB–UV-B phototherapy resulted in clinically apparent, statistically significant superior and faster repigmentation compared with NB–UV-B monotherapy. The response was more noticeable in patients with SPTs IV to VI.Trial Registration clinicaltrials.gov Identifier: NCT01430195
Article
Background: Recently, the abnormal presence of thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) has been reported in vitiligo patients, but presence of TG-Ab and TPO-Ab in patients of different ages and gender, and its association with vitiligo and thyroid autoimmunity has rarely been reported. The aim of our research was to determine whether vitiligo was associated with thyroid autoimmunity and figure out its relationship with age and gender. Materials and Methods: We analyzed TG-Ab, TPO-Ab in age and gender matched 87 vitiligo patients and 90 healthy controls, the patients of vitiligo who were positive for the presence of TG-Ab and TPO-Ab were followed up to confirm autoimmune thyroid disease subsequently. Results: Results showed that the frequencies of TG-Ab (23.0%, 20/87) positivity and TPO-AB (24.1%, 21/87) in vitiligo patients were significantly higher than that in healthy controls (P < 0.05). Moreover, The positivity for of TG-Ab and TPO-Ab was higher in 11-20-year age group and 21-40-year age group than that in age matched healthy controls. We found female patients with vitiligo had higher positive frequencies of TG-Ab and TPO-Ab than healthy female controls. (34.1% vs. 8.8% and 34.1% vs. 11.1%, P = 0.000 and P = 0.011). When 20 patients with TG-Ab and TPO-Ab positivity were followed up for three monthes, 14 of them (70%) were diagnosed as having autoimmune thyroid disease compared with age-matched healthy controls (16.7%, χ2 = 5.4, P = 0.02). Conclusion: TG-Ab and TPO-Ab are likely to be found in female teenagers with vitiligo, and are relevant with respect to subsequent development autoimmune thyroid disease.
Article
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.
Article
Although the outcomes of various treatment modalities for vitiligo have been studied extensively, the influence of the participant's characteristics on treatment response has not been thoroughly investigated. Therefore, we retrospectively investigated treatment effects and their association with clinical characteristics in Japanese patients with vitiligo. The charts of patients with vitiligo treated in our institution were reviewed. Clinical response was evaluated as a marked response rate, defined as repigmentation in >75% of the initial lesional area. 162 patients were treated with phototherapy, while 69 were treated with topical mono-therapy. The patients treated with phototherapy and those treated with both phototherapy and topical treatment demonstrated significantly higher clinical response rates compared to patients treated solely with topical mono-therapy (marked response rate: 19.1% vs. 5.8%, P<0.05; and 23.5% vs. 5.8%, P<0.01, respectively). Among the phototherapy-treated patients, younger subjects (≤15 years old) were more responsive to phototherapy compared to older patients (37.0% vs. 15.6%; P=0.015). The disease subtypes did not affect treatment response. In conclusion, phototherapy appears to have a therapeutic effect superior to topical mono-therapy on both focal and generalized vitiligo, especially in younger patients. Thus, any type of psychosocially devastating lesions in a pediatric patient may be a good target for phototherapy.
Article
Vitiligo is an acquired depigmentary skin disorder of unknown etiology. Vitiligo is not only a disease of melanocytes of the skin. Human melanocytes are derived from the neural crest and are located on various parts of the body. The involvement of skin melanocytes is the most visible one, but a systemic involvement of melanocytes can be observed. Some types of vitiligo (nonsegmental vitiligo) may also be associated with various diseases, mainly with autoimmune pathogenesis. Vitiligo represents a spectrum of many different disorders with different etiologies and pathogeneses, causing a common phenotype: the loss of melanocytes and/or their products. This phenotype is always consistent with a systemic involvement.
Article
Vitiligo is a disease of pigment loss. Most investigators currently consider vitiligo to be a disorder that occurs as a result of autoimmune destruction of melanocytes, supported by identification of antimelanocyte antibodies in many patients, and the presence of comorbid autoimmune disease in patients with and family members of individuals with vitiligo. One-half of vitiligo cases are of childhood onset. This article presents a current overview of pediatric vitiligo including comorbidities of general health, psychological factors, therapeutic options, and long-term health considerations.
Article
Vitiligo is an autoimmune depigmentation disorder that is estimated to affect about 0.5% of the worldwide population. Half of all cases begin in childhood. A variety of advances occurred in the past two decades that have enhanced the management of childhood vitiligo. This article reviews recent advances in vitiligo, including a better understanding of the pathogenesis and autoimmune comorbidities, description of the psychological comorbidities, a broader range of therapeutic options.
Article
Dermatologists are frequently faced with questions from women who are breastfeeding about the safety of commonly prescribed topical and systemic medications during lactation. Safety data in lactation, particularly regarding medications that are unique to dermatology, are limited and can be difficult to locate. We have consolidated the available safety data in a single reference guide for clinicians. We review literature pertaining to the safety of common dermatologic therapies in lactation and offer recommendations based on the available evidence.
Article
Dermatologists are frequently faced with questions about the safety of commonly prescribed topical and systemic medications during pregnancy and lactation from women of childbearing age who are pregnant, considering pregnancy, or breastfeeding. Safety data, particularly regarding medications that are unique to dermatology, can be difficult to locate and are not consolidated in a single reference guide for clinicians. Parts I and II of this continuing medical education article provide a capsule summary of key points for the most commonly prescribed dermatologic medications to facilitate patient medication risk counseling in pregnancy. A summary table details safety classification data for 3 primary international classification systems: the US Food and Drug Administration, the Swedish Catalogue of Approved Drugs, and the Australian Drug Evaluation Committee. In addition, this table includes an alternative pregnancy classification system developed by a consortium of active members of teratology societies in the US and Europe detailed in Drugs during Pregnancy and Lactation: Treatment Options and Risk Assessment and a safety classification system developed for breastfeeding mothers detailed in Medications and Mother's Milk.
Article
Vitiligo is an acquired skin disorder with great social impact. It can be successfully treated using cultured autologous melanocytes transplantation. To evaluate the effect of different modalities of narrow-band ultraviolet B (NB-UVB) therapy on the outcome of cultured autologous melanocyte transplantation in treating vitiligo. Patients undergoing cultured autologous melanocyte transplantation were randomly assigned to four different study groups. Group 1 underwent 20 sessions of NB-UVB treatment before transplantation; Group 2 underwent 30 sessions of NB-UVB treatment after transplantation; Group 3 underwent 20 sessions of NB-UVB treatment before transplantation and 30 sessions after transplantation; Group 4 underwent only transplantation. Four hundred thirty-seven patients were enrolled. Group 3 responded best, more than 90% repigmentation was achieved in 81.3% of patients, and 94.8% patients experienced 50% or greater repigmentation. Statistical analysis showed that there was a highly significant difference between the four groups (χ(2) = 35.56, p < .001). Homogeneous skin color was obtained on the repigmentation areas, and no scarring or other serious side effects were observed. Cultured autologous melanocyte transplantation is an effective treatment for stable vitiligo. Combination of NB-UVB therapy with melanocyte transplantation can accelerate repigmentation of transplanted vitiliginous areas, especially if NB-UVB is given before and after transplantation.
Article
Abstract Objective: The present study was designed to evaluate if plasma maternal folate, vitamin B-12 and homocysteine levels had an effect on maternal global DNA methylation and neonatal anthropometrics in Indian pregnant women. Methods: A total of 49 participants having completed >36 weeks of pregnancy were enrolled in the study. Estimation of folate was by Ion capture assay, vitamin B-12 by Microparticle Enzyme Immunoassay, total homocysteine by Fluorescence Polarization Immunoassay and global DNA methylation using Cayman's DNA Methylation EIA kit. Results: Folate and vitamin B-12 were inversely correlated to homocysteine in pregnant women consuming vegetarian and non-vegetarian diet. No difference in global DNA methylation was found between the vegetarian and non-vegetarian pregnant women. Folate, vitamin B-12 did not show association with global DNA methylation, however plasma total homocysteine of the vegetarian group showed significant correlation to global DNA methylation (r(2)=0.49, p=0.011). Plasma total homocysteine was inversely related to tricep skinfold (r(2)=-0.484, p=0.01) and chest circumference (r(2)=-0.104, p=0.04) of neonates in vegetarian group. Conclusion: Moderate vitamin B-12 deficiency in vegetarian pregnant women might be the cause of hyperhomocystenemia, hypermethylation when compared vitamin B-12 sufficient non-vegetarian group.
Article
Vitiligo significantly affects quality of life (QOL) in adults, but little is known about the effect on QOL of pediatric vitiligo and whether the extent, distribution, and duration of vitiligo are associated with QOL. We performed an online parental questionnaire-based study (N = 350) regarding children ages 0 to 17 years with vitiligo, including validated questions about body surface area (BSA), distribution, and age of onset of vitiligo, associated symptoms, and QOL using the Children's Dermatology Life Quality Index (CDLQI). Vitiligo negatively affected numerous aspects of and total CDLQI score (median 3.0, interquartile range 5.0). Their vitiligo lesions did not bother only 4.1% of teenagers ages 15 to 17 years, versus 45.6% of children ages 0 to 6 years and 50.0% of those ages 7 to 14 years (p < 0.001). There was no association between the child's age and whether the child's vitiligo bothered the parents (p = 0.27). The most bothersome sites of vitiligo lesions for children and parents were the face (25.6% and 37.4%, respectively) and legs (26.2% and 26.2%, respectively). Eighty-two patients (30.1%) reported itching and painful skin within the past week. Using multivariate ordinal logistic regression models, it was found that an affected BSA of more than 25% was associated with self-consciousness, difficulty with friendships and schoolwork, and teasing and bullying. Lesions on the face and arms were associated with teasing and bullying. The extent of vitiligo is associated with QOL impairment in children and adolescents, especially self-consciousness, but also bullying and teasing. Different distributions of vitiligo lesions are associated with different aspects of QOL impairment. Teenagers ages 15 to 17 years seem to experience the most self-consciousness of all pediatric age groups.
Article
The Evidence Based Update (EBU) meetings are annual one day meetings held by the Centre of Evidence-Based Dermatology (CEBD) at the University of Nottingham. The aim of the meeting is to discuss high quality evidence, mainly in the form of systematic reviews and randomised controlled trials (RCTs), on a different topic each year. The meetings are designed to be interactive with a panel discussion between international experts and delegates forming a key part of the meeting. The 11(th) EBU meeting was on vitiligo and took place on 23(rd) May 2013 in Loughborough, UK. The most recent research including new and unpublished studies was presented on the classification of vitiligo, the evidence behind different treatment options and current guidelines for vitiligo. This article is protected by copyright. All rights reserved.
Article
Vitiligo is characterized by a loss of cutaneous and mucosal pigmentation and often is associated with psychological distress. Depigmentation therapy can be used to eliminate residual pigment, thereby creating an evenly depigmented skin tone. Patients often seek depigmentation therapy to even their skin tone when a large body surface area is affected by vitiligo or when exposed areas (eg, face, hands) are affected and do not respond to repigmentation therapy. Psychological screening of patients is recommended when considering depigmentation therapy for vitiligo. We report the case of a 24-year-old man with vitiligo who sought depigmentation therapy and withheld crucial information regarding his psychiatric and medication history. We also provide guidelines for a rational approach to psychocutaneous screening of patients with vitiligo seeking depigmentation therapy.
Article
Segmental vitiligo (SV) is usually characterized by a unilateral-dermatomal distribution, earlier onset and rapid progression followed by stabilization. The response to phototherapy in patients with SV is limited. We evaluated the treatment response in 39 cases of SV according to disease duration. Ten cases (50.0%) of Group 1 (duration ≤ 5 months) and five cases (26.3%) of Group 2 (duration > 5 months) showed more than 50% repigmentation. Contrary to previous reports, patients in our study responded well to medical treatments like oral steroids, topical calcineurin inhibitors and phototherapy when treated early after onset. The results suggest that early treatment is important.
Article
Vitiligo is an acquired pigment disorder in which depigmented macules result from the loss of melanocytes from the involved regions of skin and hair. The color dissimilarity on the cosmetically sensitive regions frequently induces quality of life impairment and high willingness to pay for treatment in patients with vitiligo. The Vitiligo Japanese Task Force was organized to overcome this situation and to cooperate with the Vitiligo Global Issues Consensus Conference. This guideline for the diagnosis and treatment of vitiligo in Japan is proposed to improve the circumstances of Japanese individuals with vitiligo. Its contents include information regarding the diagnosis, pathogenesis, evaluation of disease severity and effectiveness of treatment, and evidence-based recommendations for the treatment of vitiligo. The therapeutic algorithm based on the proposed recommendation is designed to cure and improve the affected lesions and quality of life of individuals with vitiligo.
Article
Vitiligo is an acquired, depigmenting skin disease with still unclear, multifactorial etiopathogenesis. However, there is growing evidence that vitiligo affects not only the skin but it may also be connected with metabolic abnormalities, including glucose intolerance and lipid abnormalities, all of which confirms the systemic nature of the disease. Recently, it has been shown that melanocytes, especially those found in the adipose tissue, due to their ability to decrease inflammation and oxidative damage, are capable of preventing the metabolic syndrome. The article presents updated knowledge on potential metabolic disturbances in vitiligo.
Article
Background: Vitiligo is a frequent dyschromia characterized by achromic macules that reflect the absence of melanocytes. It affects 1% of the general population. Treatment of vitiligo is a challenge. Recently, topical calcipotriol has been claimed to be effective, either as monotherapy or as part of combination therapies. Objective: To evaluate the efficacy and safety of calcipotriol 0.005%/betamethasone dipropionate 0.05% ointment in the treatment of vitiligo. Methods: Thirty-one patients with vitiligo were enrolled in our study. The mean age of the patients was 32.6 + 11 years (range 18-56 years) and the mean duration of vitiligo was 3.7 + 5.8 years (range 0.07-30 years). Patients were treated with topical calcipotriol 0.005%/betamethasone dipropionate 0.05% ointment twice a day for at least 12 weeks, and the degree of repigmentation was analyzed using digital photography at baseline and at weeks 4, 8, and 12. The response was evaluated as excellent (76%-100%), moderate (51%-75%), mild (26%-50%), minimal (1%-25%), or no response. Possible adverse effects during the treatment period were also noted. Results: Three patients (9.7%) had an excellent response, six patients (19.4%) had a moderate response, eight patients (25.8%) had a mild response, seven patients (22.6%) had a minimal response, and seven patients (22.6%) had no response. Patients at a progressive phase responded better to this ointment than patients at a stable phase (P=.005). The correlations between response rate and the duration of the disease were not significant (P=.791). Four adverse events related to the ointment were reported (pruritus, n=2; acne, n=2). Conclusion: Calcipotriene 0.005%/betamethasone dipropionate 0.05% ointment is effective and well tolerated in the treatment of patients with vitiligo.
Article
Cutaneous metabolism and pharmacology have been the focus of increased scientific inquiry in the past 2 decades. However, in the past few years, attention has been focused specifically on the effects of topically applied drugs in infants as different qualitatively or quantitatively from their effects in adults. Prior to 1972, it was known that brain damage occurred in animals with prolonged blood levels of 1 μg/ml hexachlorophene, and that washing newborn babies with a standard 3% hexachlorophene liquid soap for 3–5 days resulted in significant blood levels of the compound. However, this knowledge was not disseminated widely enough to prevent the tragic deaths of infants after the use of baby powder contaminated with 6.6% hexachlorophene [1]. This incident highlighted the need for increased understanding of drug effects not only from the viewpoint of the skin as a target organ, but also of percutaneous penetration and resultant blood levels; the affinity of other body tissues for drugs and their metabolites; metabolites which may result from the effect of the skin itself acting on the drug; and the infant's much greater ratio of surface area to body weight, allowing the infant to percutaneously absorb proportionately greater quantities of topical medication than an adult. Although tissue distribution of most drugs has not been studied in infants, it is known that such distribution often depends on age. For example, in infants and children with a given plasma level, of drugs such as barbiturates, morphine and tetracycline, the brain tissue level may exceed that of the adult. Thus, drugs and chemicals that penetrate infant skin may produce effects different than those penetrating adult skin.
Article
To the Editor: In a recent pooled analysis of vitamin D dose requirements for fracture prevention, Bischoff-Ferrari and colleagues (July 5 issue)(1) reanalyzed data from clinical trials by taking into account vitamin D supplementation taken by participants in addition to the study medication. This reanalysis provides a more accurate estimation of the vitamin D intake. However, the results are inconclusive because the authors did not mention sunlight exposure, which is the natural physiological source of vitamin D. This substance is not a "vitalamine" but it is a secosteroid hormone that is normally produced by the skin. No dietary intake is . . .
Article
The etiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental (SV) and non segmental (NSV) vitiligo has been developed by the members of the Vitiligo European Task Force (VETF) and other colleagues. It summarizes evidence-based and expert-based recommendations (S1 level).
Article
The literature was searched for publications on minerals and vitamins during pregnancy and the possible influence of supplements on pregnancy outcome. Maternal iron (Fe) deficiency has a direct impact on neonatal Fe stores and birth weight, and may cause cognitive and behavioural problems in childhood. Fe supplementation is recommended to low-income pregnant women, to pregnant women in developing countries, and in documented deficiency, but overtreatment should be avoided. Calcium (Ca) deficiency is associated with pre-eclampsia and intra-uterine growth restriction. Supplementation may reduce both the risk of low birth weight and the severity of pre-eclampsia. Gestational magnesium (Mg) deficiency may cause hematological and teratogenic damage. A Cochrane review showed a significant low birth weight risk reduction in Mg supplemented individuals. Intake of cereal-based diets rich in phytate, high intakes of supplemental Fe, or any gastrointestinal disease, may interfere with zinc (Zn) absorption. Zn deficiency in pregnant animals may limit fetal growth. Supplemental Zn may be prudent for women with poor gastrointestinal function, and in Zn deficient women, increasing birth weight and head circumference, but no evidence was found for beneficial effects of general Zn supplementation during pregnancy. Selenium (Se) is an antioxidant supporting humoral and cell-mediated immunity. Low Se status is associated with recurrent abortion, pre-eclampsia and IUGR, and although beneficial effects are suggested there is no evidence-based recommendation for supplementation.
Article
  Topical corticosteroids (TCS) are first-line therapeutic agents for atopic dermatitis (AD). Some patients express irrational fear and anxiety about using TCS, which leads to poor outcomes for AD. Although it is important to understand the factors underlying steroid phobia so that its effects can be minimized, few studies have addressed this subject. Here, we used a questionnaire to investigate predictive factors for steroid phobia in the caregivers (usually mothers) of children with AD. We studied 436 children with AD (mean age 47.6 mos, range 2-236 mos) who newly visited our AD outpatient unit. The caregivers were asked to complete a medical history questionnaire regarding AD. Steroid phobia was analyzed for correlations with other patient and caregiver variables. Overall, 38.3% of the caregivers were reluctant to use TCS on their children's skin. Patient characteristics female sex (odds ratio [OR] = 1.85 vs male; p = 0.005), child's paternal history of AD (OR = 1.94; p = 0.03), and frequent changing of clinics (OR = 1.25; p = 0.03) were predictive factors for steroid phobia. AD severity did not correlate with steroid phobia. Our findings suggest that greater attention to the patient's sex and clinical background of patients with AD is important to the success of AD therapy, regardless of AD severity.
Article
Phototherapy is a mainstay of vitiligo treatment and has varying rates of efficacy. Narrowband ultraviolet (UV) B (NB-UVB) and UVA have been used for decades, but it is only recently that monochromatic excimer light (MEL) was developed for use in dermatology and adapted for the treatment of vitiligo. The specific 308-nm radiation wavelength is delivered in a targeted form by the xenon-chloride excimer laser and is also available in an incoherent form that is commonly referred to as the excimer lamp. MEL administered by both laser and lamp has shown efficacy superior to NB-UVB for the treatment of vitiligo and induces more changes at the cellular level than conventional UVB modalities. The excimer laser is effective in adults and children with vitiligo in all skin types as monotherapy or in combination with other established vitiligo therapeutics. Treatment regimens studied included excimer laser two to three times weekly for up to 36 weeks. Patients commonly achieved > 75% repigmentation. The laser has also been used in combination with topical corticosteroids, calcineurin inhibitors and vitamin D analogues, as well as surgery, thus further expanding treatment options for patients with vitiligo. The excimer lamp has been used for treatments one to three times a week for up to 24 weeks and was found to be equal to excimer laser in a head-to-head comparison. It has also been used in combination with topical corticosteroids and oral vitamin E. Both MEL modalities have a limited adverse side-effect profile. Long-term effects are yet to be determined; however, based on available data on UVB phototherapy as well as the properties of MEL devices, there is probably only a minimal increased malignancy risk.
Article
During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner's phenomenon (KP); and 'autoimmune vitiligo'. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental vitiligo be classified separately from all other forms of vitiligo and that the term 'vitiligo' be used as an umbrella term for all non-segmental forms of vitiligo, including 'mixed vitiligo' in which segmental and non-segmental vitiligo are combined and which is considered a subgroup of vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that 'autoimmune vitiligo' should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of vitiligo likely involves autoimmune or inflammatory mechanisms.
Article
Vitiligo vulgaris is an autoimmune pigmentary disorder with no universally efficacious therapeutic options. Separate applications of calcipotriene ointment 0.005% and topical corticosteroid ointments have been successful in the repigmentation of vitiligo. We sought to examine the efficacy of a combination calcipotriene 0.005%-betamethasone dipropionate 0.064% ointment in the repigmentation of vitiligo. An institutional review board-approved retrospective chart review was conducted in 13 pediatric and adult patients with vitiligo treated with calcipotriene 0.005%-betamethasone dipropionate 0.064% ointment once daily for at least 2 months. Two of 3 children had 76% to 100% repigmentation of facial vitiligo with once-daily usage after 2 months. Of the 10 adults (aged 28-55 years), 1 had 100% facial repigmentation in 3 months, 1 had 76% to 99% facial repigmentation in 5 to 9 months, and 2 had 26% to 50% repigmentation in 3 months. Twelve patients developed some facial repigmentation. No patients experienced atrophy, telangiectases, or lesion enlargement during treatment. Combination calcipotriene 0.005%-betamethasone dipropionate 0.064% ointment shows promise as a once-daily vitiligo therapy. Adult and pediatric facial vitiligo patients may see repigmentation as early as 2 months after initiation of therapy. Children may experience a better response, but larger studies are needed.
Article
From a therapeutic standpoint, vitiligo is still regarded by many physicians as a simple problem of regenerative medicine, with the main aim to repopulate the depigmented skin with functional melanocytes from the margins of the lesions or from intact progenitors in hair follicles. However, recent research in vitiligo suggests that various local triggers alert the skin immune innate system and may precede adaptive immune responses targeting melanocytes. This scenario is close to that of other common skin inflammatory disorders like psoriasis and atopic, and suggests to target as a priority this clinically silent inflammatory component of he disease. This perspective highlights possible targets for intervention.
Article
Phototherapy is used for the medical care of cutaneous conditions that do not respond to topical or systemic medical agents, and for conditions that require broad exposure to UV as a stabilizing agent for disease. Numerous wavelengths and delivery devices of ultraviolet light are used in childhood. This article is a brief overview of the medical usage of phototherapy in childhood. In the neonatal nursery blue light (459-460 nm) is used to reduce bilirubin levels and prevent kernicterus. While psoralens and UVA (PUVA) has been demonstrated to be efficacious in a variety of pediatric skin conditions, narrowband UVB therapy (311 nm) has largely replaced psoralens and UVA as initial choice in full-body phototherapy for children. The latter is easier to deliver, with less resultant erythema than systemic psoralens and UVA which requires strict use of 24 hour protective eyewear. Narrowband UVB is therefore preferred for stabilization and clearance of a variety of inflammatory and autoimmune conditions especially atopic dermatitis, psoriasis and vitiligo. Conditions with lymphocytic infiltration, including mycosis fungoides, alopecia areata and pityriasis lichenoides can improve with Narrowband UVB as well. Alternatively, localized delivery of Narrowband UVB can be performed using the excimer laser (308 nm), which has been described for the therapy of vitiligo and alopecia areata in childhood. Some diseases with dermal infiltration including morphea and mastocytosis may do better with Psoralens and UVA or UVA1. Delivery of psoralens can also be performed topically for said conditions and in the setting of alopecia areata, thereby limiting UVA exposure, while retaining efficacy. Phototherapy can be a helpful adjunct in pediatric skin disease, but is limited by compliance issues. Parents can act as partners in the safe and effective delivery of phototherapy by standing outside the booth or inside with the child to ensure lack of movement and to aid in maintenance of eyewear. Choice of type of phototherapy and close monitoring, with parental partnership, is the key to successful treatment.
Article
Background Ultraviolet radiation following punch grafting may stimulate the migration of melanocytes from the grafts into the vitiliginous skin, thereby increasing the rate of repigmentation. We compared the effects of the 308-nm xenon chloride excimer laser (EL) vs. narrow-band ultraviolet B (NB-UVB) after punch grafting in patients with vitiligo. Objectives The aims of this study were to evaluate (i) repigmentation (%); (ii) treatment satisfaction; and (iii) patient preferences for EL vs. NB-UVB therapy after punch grafting in vitiligo. Methods Fourteen patients were treated with the punch-grafting technique on two symmetrical vitiligo patches. Starting 1 week after the punch grafting, the vitiligo patches were treated twice a week during 3 months, with EL on one side and with NB-UVB on the other side. Repigmentation (%) was measured by a digital image analysis system. Patients’ satisfaction and preference for treatment were also assessed. Results Whereas both treatment modalities induced repigmentation, no statistically significant difference was found in grade of repigmentation after 3 months. With EL, 71.4% lower cumulative dose was reached. Patients were significantly more satisfied with NB-UVB and preferred it over EL. Conclusions The choice between EL and NB-UVB cannot solely be based on repigmentation, but rather on other factors, such as patients’ preferences. However, given the lower UV dose of EL, we recommend its use in vulnerable populations, such as in small children and patients with sun-damaged skin with a history of long-term UVB treatment.
Article
Vitiligo vulgaris is a chronic autoimmune depigmenting disorder affecting individuals of all skin colors. Lesions are commonly noted in the periorificial face and over the upper and lower extremities in areas of friction. Although there have been many published reports of successful therapies for vitiligo, few have assessed differential response based on skin color. To determine if topical tacrolimus is more effective at treating vitiligo in individuals of color. An IRB-approved chart review of patients with a diagnosis of vitiligo was conducted including patients seen between May 2001 and April 2006. Patients with vitiligo were treated with tacrolimus 0.03% for children ages 2-15 years of age and tacrolimus 0.1% ointment for individuals 16 years of age or older, applied twice-daily to all hypopigmented or depigmented lesions. A review of clinical features, Fitzpatrick skin type and response to topical tacrolimus were recorded. Topical tacrolimus was effective in all Fitzpatrick skin types, with superior efficacy on body lesions in individuals of Fitzpatrick types 3-4 (Fisher exact test, P=0.03). Further, individuals with Fitzpatrick type 3-4 skin had shorter interval to greater than 75 percent improvement of lesions on the body (Kaplan-Meier Log-rank, P=0.03) and head and neck (P=0.016). Topical tacrolimus is an effective treatment for vitiligo irrespective of skin tone, with greatest benefit in Fitzpatrick type 3-4 skin. Repigmentation of lesions on the head and neck is superior to repigmentation of the body and extremities in all racial subgroups.
Article
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. To assess efficacy and safety of these two therapies compared with each other and with placebo. 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. 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. 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.
Article
Topical corticosteroids and phototherapy are the conventional treatments of vitiligo. However, the acrofacial and segmental types are often unresponsive to these treatments. Nowadays, a few studies have been conducted on efficacy of topical tacrolimus in treatment of vitiligo including vulgaris and segmental types. Nevertheless, the acrofacial type has never been investigated with this topical therapy. The aim of our study is to evaluate the effectiveness of 0.1% tacrolimus ointment in patients including all types of vitiligo. Forty-two patients with vitiligo (22 adults, 20 children) were enrolled in this study. They were treated with 0.1% tacrolimus ointment twice daily for 6 months. Of these 42 patients, 38 of them completed the treatment process. The mean age of the patients was 27.8 years. The response rate was 76.09%. The vulgaris and focalis had a maximum response rate of 94.12%. The response rates for segmentalis and acrofacialis were 76.92% and 56.25% respectively. Concerning the response, age groups, types and location of vitiligo, there was significant difference in all variables (P = 0.001, P = 0.001, P = 0.025, respectively). Children had approximately nine times higher odds (95% CI = 1.09, 81.88) of having better response to the treatment than adults. The disease duration of 5 years or less also showed a better response. In conclusion, topical tacrolimus can be used for the treatment of patients with vitiligo. We recommend that, other than in the vulgaris type, topical tacrolimus may be considered as a treatment for two difficult to treat types of vitiligo, acrofacialis and segmentalis, before considering other modalities.
Article
Numerous modalities have been used to treat vitiligo in children. Up to now, phototherapy and topical corticosteroids are the most commonly used treatments for adult vitiligo but studies evaluating the efficacy of these treatments in the pediatric population remain insufficient. This study was a retrospective review to evaluate the efficacy and safety of 308-nm excimer laser treatment in 30 childhood vitiligo patients. Thirty vitiligo patients with 40 vitiligo patches were evaluated after the cessation of 308-nm excimer laser treatment. Seventeen patients (56.7%) with 20 patches (50%) achieved an acceptable degree (>50%) of repigmentation at the end of the treatment, with five patches (12.5%) showing >75% of repigmentation. The treatment response showed anatomical preferences, favoring the face, neck and trunk. However, the treatment response did not correlate to the cumulative dose or duration of treatment. Side effects occurred in nine patients, but were transient and minimal. The results of this study shows that the 308-nm excimer laser can be an effective and promising device for the treatment of various vitiligo types, other than generalized, in childhood.
Article
Vitiligo is a common depigmenting disorder affecting about 1-2% of the world population. Approximately half of the affected individuals develop the disease before adulthood. Etiologic hypotheses for vitiligo include biochemical, neural and autoimmune mechanisms. The most compelling of these suggests a combination of genetic and immunologic factors that result in an autoimmune melanocyte destruction. We reviewed studies carried out on various treatment modalities used in childhood vitiligo. Topical corticosteroids were found to have excellent repigmentation rates, whereas calcineurin inhibitors have comparable efficacy and a better safety profile compared with topical corticosteroids. These two groups of topical medications are good first-line treatment modalities for localized vitiligo. For the treatment of generalized vitiligo, phototherapy has excellent efficacy. Narrow-band ultraviolet B (UVB) has better overall repigmentation rates and safety profile than either topical or oral psoralens and ultraviolet A (PUVA). Other treatment modalities may be considered depending on a patient's specific condition, such as surgical options and depigmentation. With adequate sun protection, the option of no treatment with or without corrective camouflage, is an innocuous alternative to any of these treatment modalities.