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Calcipotriene and Corticosteroid Combination Therapy for Vitiligo
Abstract
Corticosteroids and photochemotherapy, using a combination of psoralen and ultraviolet A (PUVA) exposure, are the most widely prescribed therapies for vitiligo. These treatments are not uniformly effective and many patients have inadequate responses. Calcipotriene has been shown to be effective in adults and children with psoriasis when used as monotherapy and in combination with corticosteroids and phototherapy. We hypothesized that since the mechanisms of action for calcipotriene and corticosteroids are different, patients may develop more repigmentation with a combination of the two agents, while decreasing the side effects from both agents.
Twelve patients with vitiligo (average age 13.1 years) were advised to use topical corticosteroids in the morning and topical calcipotriene in the evening. Of the 12 patients, 83% responded to therapy, with an average of 95% repigmentation by body surface area. Four of the patients who responded had previously failed trials of topical corticosteroids alone. All of the patients in this group had repigmentation. Eyelid and facial skin responded best to this therapy. None of the patients had adverse reactions to the treatment. Our results show that topical calcipotriene in combination with corticosteroids can repigment vitiligo, even in those patients who were previous topical corticosteroid failures.
... Penggunaan kombinasi kortikosteroid topikal kelas 5, 3 atau 2 dengan calcipotriol menunjukkan keberhasilan terapi sebesar 87% dan repigmentasi rata-rata mencapai 95%. 11 Efikasi dan keamanan kombinasi tersebut lebih baik dibandingkan dengan terapi tunggal. ...
... 7 Pemakaian krim calcipotriol 2 kali sehari menghasilkan repigmentasi lebih dari 25 % pada 60% pasien. 11 Pengolesan krim tersebut dilanjutkan dengan berjemur di bawah sinar matahari selama 10 menit menimbulkan repigmentasi sedang sampai baik pada 77% pasien anak. 15 Kombinasi calcipotriol topikal dengan kortikosteroid topikal menghasilkan repigmentasi yang lebih cepat dengan pigmentasi yang stabil. ...
... 15 Kombinasi calcipotriol topikal dengan kortikosteroid topikal menghasilkan repigmentasi yang lebih cepat dengan pigmentasi yang stabil. 11 Calcipotriol topikal juga dapat dikombinasikan dengan fototerapi NB-UVB atau laser excimer 308 nm. Efek samping pemakaian krim calcipotriol berupa hiperpigmentasi dan iritasi di daerah sekitar lesi. ...
... Therefore, they concluded this ointment is and effective alternative during childhood especially in head and neck area. [11] In Brazil, Tamler et al. reported 75% in head and neck and 27% in other regions responsive to this ointment. [1] Udompataikul et al. in Thailand indicated 94%, 76 and 56% responsiveness of vulgaris -focalis, segmentalis, and acrofacialis pigments respectively. ...
... In the present study, complications or side effects do not seen except slight irritation in 3 cases which is in line with findings of Travis and Silverberg who reported slight irritation in 2 cases. [11] This finding approves tacrolimus preference in compare to similar medications. As steroids are one of most common effective medicines in the treatment of vitiligo's through creating immunosuppressive and anti-inflammatory effect improves pigments. ...
Vitiligo is one of the most primitive well-known dermatoid disorders with different suggested therapies. Therefore, this study investigated the efficiency and safety of topical tacrolimus in treatment of patients with vitiligo. This study was a clinical randomized designed study pre- post-test method, has been conducted on thirty cases with vitiligo who have referred to polyclinic and dermatology clinic. Participant's evaluated and demographic information recorded in designed checklist. In the next stage, the disease activity scored by vitiligo index disease activity system. Photography and depigmentation percent has recorded before treatment and further in 4th, 8th, 12th, 16th, 20th, and 24th weeks. Finally, gathered data compared through SPSS-20 software. The final sample comprised 30 persons including: 12 men (40%) and 18 women (60%). The average of patient's age in this study was 26/13 ± 18/20 (2-76-year-old). Eleven persons was ≤15 years old and rest was older than 15. Sixty-six lesions have funded in patients that maximum has accrued on face and neck (37/87%) and trunk (21/21%). In addition, minimum of lesions is related to genitalia (9/09%). In the in 4th, 8th, 12th, 16th weeks, improvement in face and neck had increased significantly, into the past weeks. In the 20th and 24th weeks, the improvement has increased although it was not significant enhancement. Also about trunk, in the 4th week the improvement does not have significant increasing in compare to the past week. In the eighth, 12th, 16th, 20th, and 24th weeks the improvement has been increased significantly in compare to the past weeks. Although in the case of limbs and genitalia, the improvement was lower. There was no significant difference between male and females and age. Although the improvement was, slow in older persons. Study results, has presented applying topical tacrolimus in vitiligo, particularly in face and neck, could be effective and does not seen any specified adverse effects during consumption of tacrolimus, it could be effective in decreasing effects in use of corticosteroid.
... Seven studies were retrieved describing the use of calcipotriol or calcipotriol/betamethasone as monotherapy, including one randomized controlled trial (RCT), five open-label trials, one right-left comparison trial, and one case report with a total of 199 patients. [17][18][19][20][21][22][23][24] Calcipotriol alone does not appear to be effective in producing repigmentation and is inferior to corticosteroid monotherapy. 20,21 In a prospective right-left comparison of 24 patients, 87.5% had no response to calcipotriol applied once daily. ...
... In another study, the use of calcipotriol in the evening and a class 2/3 steroid in the morning produced 95% repigmentation in 83% (10 of 12) of patients after 3 to 7 months. 22 Higher rates of adverse events were noted with the use of betamethasone or clobetasol, including erythema, lesional atrophy, xerosis, and acneiform eruption. 20,21 In summary, calcipotriol monotherapy is unlikely to be effective for the treatment of vitiligo (Level 2a evidence). ...
Background:
Topical vitamin D is approved by the US Food and Drug Administration for the treatment of psoriasis but is also used off-label in the treatment of a variety of cutaneous diseases despite a lack of evidence-based guidelines.
Objective:
The objective of this study was to provide evidence-based clinical guidelines for the off-label use of topical vitamin D in the treatment of dermatologic disease.
Methods:
A systematic literature review was conducted via the MEDLINE, Embase, and CENTRAL databases for off-label uses of topical vitamin D analogues in the treatment of dermatologic disease other than psoriasis. The data were synthesized, and evidence-based recommendations were rendered according to the highest level of evidence available.
Results:
A total of 165 articles met the inclusion criteria. A moderate to strong recommendation was given for the use of topical vitamin D in combination with corticosteroids and phototherapy in vitiligo and as monotherapy for various ichthyoses, morphea, pityriasis alba, prurigo nodularis, and polymorphous light eruption. There is evidence showing that topical vitamin D is ineffective in the treatment of actinic keratosis, seborrheic keratosis, lichen planus, seborrheic dermatitis, alopecia areata, chemotherapy-induced alopecia, and hypertrophic scars.
Conclusion:
Topical vitamin D analogues have an important role in the off-label treatment of dermatologic disease, but higher quality studies are still required.
... Vitamin D also influences the release of various growth factors and cytokines that promote the survival and proliferation of melanocytes [24]. Elevated levels of thioredoxin have been associated with abnormal calcium uptake in the keratinocytes and melanocytes of vitiligo-affected skin, which can potentially inhibit melanogenesis by reducing tyrosinase activity [25][26][27]. While it is crucial for many people to consume foods fortified with vitamin D and obtaining a little sun exposure is important for establishing a healthy vitamin D level, certain populations, such as the elderly, obese individuals, darkskinned populations, and breastfed newborns, may require dietary supplements to meet their vitamin D requirements [28][29][30]. ...
Vitamin D is one significant prohormone substance in human organ systems. It is a steroidal hormone produced in the skin upon exposure to UVB rays. This paper presents a systematic review of the utilization of topical vitamin D, specifically cholecalciferol, calcipotriol, and tacalcitol, in the treatment of vitiligo. It considers the role of vitamin D in stimulating the synthesis of melanin and melanogenesis, which can help with the process of repigmentation. The inclusion of calcipotriol or tacalcitol in Narrowband Ultraviolet Phototherapy (NB-UVB) has shown the potential to enhance therapeutic outcomes for vitiligo. However, their effectiveness in combination with Psoralens Long Wave Ultraviolet Radiation (PUVA) and Monochromatic Excimer Light (MEL) treatment for vitiligo is limited. In contrast, combining topical corticosteroids with vitamin D analogues has demonstrated superior efficacy in treating vitiligo compared to using vitamin D analogues alone, while also providing the added benefit of reducing corticosteroid-related adverse effects. In addition, treating stable vitiligo with topical cholecalciferol and microneedling has shown success. Future studies are needed to ascertain an efficient method of administering vitamin D topically as an anti-vitiligo agent.
... They are used as monotherapy or combined with exposure to narrow-band ultraviolet B (NB-UVB) phototherapy, sunlight [27], or topical corticosteroids [28]. For the children who had previously failed trials of topical corticosteroids alone, the combination of the two agents might be more efficacious [23]. ...
... -Calcipotriol: se lo emplea asociado a UVA o PUVA dando lugar a una repigmentación más precoz y mayor, con menor dosis de UV acumulada 13,219,20 . También hay reportes de uso combinado con clobetasol con buenos resultados incluso en casos que no respondieron a corticoides 13,21 . No parece ser efectivo como monoterapia ni asociado a UVB1, 19 . ...
... Current therapies exhibit considerable efficacy, but often the total repigmentation is not achieved [4]. One of the most common treatments involves the application of psoralens associated with ultraviolet (UV) light A exposure, topical corticosteroids, narrowband ultraviolet light B, which unfortunately cause important side effects [5]. ...
0.5–1% of the world's population is affected by vitiligo, a disease characterized by a gradual depigmentation of the skin. Baicalin and berberine are natural compounds with beneficial activities, such as antioxidant, anti-inflammatory and proliferative effects. These polyphenols could be useful for the treatment of vitiligo symptoms, and their efficacy can be improved by loading in suitable carriers. The aim of this work was to formulate and characterize baicalin or berberine loaded ultradeformable vesicles, and demonstrate their potential as adjuvants in the treatment of vitiligo. The vesicles were produced using a previously reported simple, scalable method. Their morphology, size distribution, surface charge and entrapment efficiency were assessed. The ability of the vesicles to promote the permeation of the polyphenols was evaluated. The antioxidant and photoprotective effects were investigated in vitro using keratinocytes and fibroblasts. Further, the stimulation of melanin production and tyrosinase activity in melanocytes after treatment with the vesicles were assessed. Ultradeformable vesicles were small in size, homogeneously dispersed, and negatively charged. They were able to incorporate high amounts of baicalin and berberine, and promote their skin permeation. In fact, the polyphenols concentration in the epidermis was higher than 10%, which could be indicative of the formation of a depot in the epidermis. The vesicles showed remarkable antioxidant and photoprotective capabilities, presumably correlated with the stimulation of melanin production and tyrosinase activity. In conclusion, baicalin or berberine ultradeformable vesicles, and particularly their combination, may represent promising nanosystem-based adjuvants for the treatment of vitiligo symptoms.
... Potent topical steroids can readily cause atrophy of the thin skin of the eyelid; indeed, prolonged use of topical steroids on eyelids can result in exposure of the eyes to steroids, occasionally causing increased intraocular pressure and cataract formation [47]. However, other topical therapies, such as tacrolimus and calcipotriene, have been found safe and effective on eyelids (Fig. 42.8) [48,49]. ...
Vitiligo at the mucocutaneous junctions of the lips, eyelids and genitals is a therapeutic challenge, as it is often recalcitrant to medical therapies and poses technical difficulties when planned to be treated surgically. The following procedures may be useful for the management of lip vitiligo: suction blister epidermal grafts, minigrafting, thin and ultra-thin split-thickness grafts, cell-based therapies for lip vitiligo, micropigmentation or tattooing, surgical excision and primary closure, surgical excision with mucosal advancement flap. The eyelids are a common site of involvement in both generalized and segmental forms of vitiligo. Various transplantation procedures have been attempted for vitiligo of the eyelids, including ultrathin, split-thickness grafts, minigrafts, suction blister epidermal grafts, non-cultured melanocyte-keratinocyte cell suspensions, and follicular grafts. Mucosal vitiligo on the glans penis poses a challenge to the treating physician for several reasons. The glans penis and inner surface of the prepuce are covered with non-keratinized epithelium.
... In progressive vitiligo, TCs may be associated to the oral ones [21]. Apart from the risks due to the steroids therapy, the protocol seems to be effective in halting the progression of the disease and in inducing skin repigmentation. ...
Vitiligo is an important skin disease of childhood, which may lead to deep psychological trauma, resulting in a poor quality of life and low self-esteem. The Authors discuss a short review of the more conventional therapies available for the treatment of vitiligo in children.
... 13 Calcipotriene is a synthetic analogue of vitamin D 3 , calcitriol: 1, 25(OH) 2 D 3 that has immunomodulating and immunosuppressive actions. 14 15,16 We observed also the efficacy of a combination of calcipotriene 0.005% -betamethasone dipropionate 0.05% ointment in the repigmentation of vitiligo but the comparison of efficacy and safety of this drg alone or in combination has not been done in Bangladesh. We conducted a clinical trial to compare the efficacy and safety of this combination in localized vitiligo. ...
Objective: To compare the efficacy and safety of topical calcipotriol ointment (0.005%) and betamethasone dipropionate (0.05%) cream, given alone and in combination, in treatment of localized vitiligo. Methods :It was a clinical trial conducted from January 2012 to August 2012. Patients of localized vitiligo attending outpatient department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University, Dhaka were the study population. In group A, 20 patients applied betamethasone dipropionate cream 0.05% in the morning and topical calcipotriene ointment (0.005%) in the evening, in group B, 20 patients applied betamethasone dipropionate cream 0.05% twice daily; In group C, 20 patients used calcipotriene ointment 0.005%. Results :in The vitiligo score in group A, B and C reduced from 26, 25 and 23, respectively to 3, 8 and 6 (p<0.05). The side effects experienced by patients at 5th follow-up were: in group A erythema (15%), dryness (15%), scaling (5%) and pruritus (5%); in group B, erythema (15%), scaling (5%), dryness (5%) and pruritus (5%); and in group C, erythema (10%) [p=0.005]. Conclusion : Both the drugs, calcipotriol and betamethasone dipropionate when used individually as monotherapy, were found to be equally effective in the treatment of vitiligo, but the combination of the two was found to be superior in efficacy. Regarding safety level, calcipotriene and betamethasone dipropionate when used individually, were found to be safer in the treatment of vitiligo, than the combination of the two.
... 5,6 Vitiligo can be cosmetically disfiguring and it is a stigmatizing condition, leading to serious psychologic problems in daily life. 7,8 Two of the major theories of the pathogenesis of vitiligo are the autoimmune theory and the autocytotoxicity theory. 9 The autoimmune theory speculates that patients with vitiligo form autoantibodies against melanocytes. ...
Vitiligo is an acquired skin disorder characterized by welldefined white patches that are often symmetrically distributed. The study was conducted to compare the efficacy of the combination of topical betamethasone dipropionate and calcipotriene with betamethasone dipropionate and calcipotriene alone in the treatment of localized vitiligo. A clinical trial was carried out with the patients of vitiligo from January 2012 to August 2012. In group A, 20 patients were applied betamethasone dipropionate cream 0.05% and topical calcipotriene ointment (0.005%), in group B, 20 patients were applied betamethasone dipropionate cream 0.05% only; In group C, 20 patients were applied calcipotriene ointment 0.005% alone. From base line percentage reduction of total lesion in 1st follow up in group A, group B and group C were 20%, 15% and 10% respectively. At 3rd follow up in group A, group B and group C it was 50%, 37% and 30% and at 5th follow up, it was 80%, 75% and 65% respectively. ANOVA test was done and found significant difference of reduction of total lesion of vitiligo among the groups (p< 0.05). At the completion of the study, each patient was separately graded the treated sides on a 6-point ordinal scale based on a global estimate of the change in vitiligo and found that, the very much improvement were 70%, 55% and 45%, much improvement were 20%, 30% and 35% and improvement were 10%, 15% and 20% in group A, group B and group C respectively. ANOVA test was found significant difference of success rate of patients of localized vitiligo among the groups (p value 0.005). Both the drugs, calcipotriene and betamethasone dipropionate when used individually, were found to be equally effective in the treatment of vitiligo, but the combination of the two was found to be superior in efficacy. DOI: http://dx.doi.org/10.3329/medtoday.v26i1.21310 Medicine Today 2014 Vol.26(1): 31-35
... The cause is unknown but may involve genetic factors, autoimmunity, toxic metabolites, and/or a higher vulnerability of melanocytes (2). It affects 0.5-2% of the population worldwide (3), it is a stigmatizing condition leading to serious psychologic problems in daily life (4). ...
... In a study including 18 children with vitiligo, complete repigmentation was reported in 10 (56%) after local application of calcipotriol (57). Significantly better results were achieved when it was combined with local corticosteroids (58). most commonly used in the management of vitiligo in adults, are less successful in children (8). ...
Vitiligo is an acquired, often hereditary skin depigmentation disorder, characterized by discrete, well-circumscribed, chalk-white macules or patches. It affects all age groups, but in more than half of the patients it occurs before the age of twenty, when self-image is being formed and social acceptance is of great importance. Although similar to the disease in adults, vitiligo in children and adolescents does have differences in epidemiology, association with other endocrine and/or autoimmune disorders, and treatment. This is a review of vitiligo in the pediatric population, emphasizing key differences with vitiligo in adults. According to the literature reports, we suggest that children and adolescents with vitiligo, especially non-segmental type, should perform annual screening for thyroid dysfunction, particularly for parameters of autoimmune thyroiditis.
... Vitiligo tedavisinde, vitamin D reseptörleri aracılığıyla immünmodülasyon ve melanogenez stimülasyonu yaparak etki gösterdiği tahmin edilmektedir. Tek başına kullanımla 18 vitiligolu çocuğun 10'unda orta düzeyde, topikal steroidle kombine kullanımla 12 çocuğun 10'unda %95 oranında repigmentasyon sağladığı gösterilmiştir 27,28 . Hafif irritasyon dışında belirgin yan etki profili yoktur. ...
Vitiligo is one of the commonest depigmented skin disorders in childhood. Clinical dermatologic examination and wood light can be helpful for diagnosis. But diagnosis is not easy everytime and some depigmented skin conditions such as depigmented nevus, ash leaf hipogmentation, postinflammatory depigmentation should be regard in differential diagnosis. Treating a patient of vitiligo is always a difficult task. Treatment options for progressive vitiligo are quite limited in pediatric patients. Systemic treatments commonly used for the disease have the potential of serious adverse effects in this age group. (Turkderm 2011; 45 Suppl 2: 117-21)
... 14 There are some reports describing the effect of calcipotriol or calcipotriene for vitiligo. [15][16][17] In this report, we have initially treated vitiligo with the topical corticosteroid and tacalcitol, and then gradually reduced topical corticosteroid to avoid the adverse effects: skin atrophy, striae and telangiectasia on the exposed areas. Topical vitamin D3 analog may control vitiligo itself, however stronger immunosuppressive effects of topical corticosteroid may contribute to rapid re-pigmentation suppressing auto-reactive lymphocytes against melanocytes. ...
We report here two cases of vitiligo vulgaris successfully treated with the combination therapy of topical steroid and vitamin D3 compound and currently maintained by vitamin D3 analog without any adverse effects: skin atrophy, striae or telangiectasia on the exposed areas. The best-known mechanism of topical vitamin D3 analog is the enhancement of keratinocytes differentiation and anti-proliferative effects. Vitamin D3 analog is also reported to suppress T-cell mediated immunity, T-cell skin recruitment, and skin infiltration via down-regulating cutaneous lymphocyte antigen expression. Furthermore, vitamin D3 compounds are known to influence melanocyte maturation and differentiation and also to up-regulate melanogenesis. Autoreactive lymphocytes against melanocytes are one of the causes. Topical vitamin D3 analog may control vitiligo itself, however stronger immunosuppressive effects of topical corticosteroid may contribute to rapid re-pigmentation suppressing auto-reactive lymphocytes. The topical combination therapy is a simple, effective and safe option for vitiligo vulgaris in sun-exposed areas.
... The use of calcipotriol combined with topical corticosteroids has been reported in
the literature. In a case series, a 75% repigmentation rate was observed in patients
that were resistant to previous treatments such as tacrolimus and topic
corticosteroids.30,31 The use of vitamin D analogues has
been associated with narrow-band UVB and Excimer LASER.22 ...
In an unprecedented effort in the field of vitiligo, a global consensus resulted on a
suggested new classification protocol for the disease. The main histopathological
finding in vitiligo is the total absence of functioning melanocytes in the lesions,
while the inflammatory cells most commonly found on the edges of the lesions are CD4+
and CD8+ T lymphocytes. Physical and pharmacological treatment strategies aim to
control the autoimmune damage and stimulate melanocyte migration from the unaffected
edges of lesions and the outer hair follicle root sheath to the affected skin;
moreover, surgical treatments can be combined with topical and physical
treatments.
... These findings led the author to hypothesize that a systemic effect of topically applied calcipotriol might have been operative. [29] Combination therapy of topical corticosteroids and calcipotriol [30] may be used to reduce the side effects of corticosteroids as well as to enhance the efficacy of calcipotriol as the latter may not be as effective when used as monotherapy. [22] Side effects of calcineurin inhibitors and calcipotriol are mild and transient and hence, easily tolerated by children. ...
Childhood vitiligo is often encountered in dermatological practice. When present in infancy or early childhood, various nevoid and hereditary disorders are to be differentiated. In many cases, familial aggregation of the disease is seen and other autoimmune disorders may be associated. Segmental presentation is more common, and limited body surface area involvement is usual in this age group. Children with vitiligo often suffer from anxiety and depression because of their unusual appearance. Management of vitiligo in children is difficult as therapeutic options are restricted when compared to that in adult patients. Selection of treatment should be careful in these patients with the aim to achieve best results with minimal side effects as well as relieving patients' and parents' anxiety.
D Vitamini Kimyasal Yapısı ve Metabolizması Hülya Cenk D Vitamini Ve Genetik Aydın Rüstemoğlu D Vitamininin Normal Serum Düzeyleri, D Vitamin Düzeylerini Etkileyen Faktörler Ve D Vitamini Yetmezliği Sabiye Akbulut Serum D Vitamininin Ölçümü Andaç Uzdoğan, Çiğdem Yücel D Vitamini Biyoyararlanımı ve Doğal Beslenme Kaynakları Atilla Çifci, Halil İbrahim Yakut Sistemik D Vitamini Tedavi Ajanları, Biyoyararlanımı ve Tedavi Yönetimi Işıl Deniz Oğuz Topikal D Vitamini Tedavisi, Tedavi Yönetimi ve Kullanıldığı Hastalıklar Dursun Türkmen Deride D Vitamini Sentezi Mekanizmaları Abdullah Demirbaş, Ömer Faruk Elmas Güneşten Koruyucu Kullanımı ve D Vitamini Nursel Dilek, Yunus Saral D Vitamininin Deri Yapısı ve Fizyolojisine Etkisi Pelin Hızlı Deri Yaşlanması ve D Vitamini Ülker Gül Psoriasis ve D Vitamini Ülker Gül Psöriatik Artrit ve D Vitamini Mehmet Uçar Atopik Dermatit ve D Vitamini Ayşegül Ertuğrul, İlknur Bostancı Mast Hücresi ve Kutanöz Mastositozda D Vitamini Selçuk Doğan, Tülin Çataklı, İlknur Bostancı Ürtiker ve D Vitamini Kemal Özyurt Kaşıntı ve D Vitamini Kübra Yüce Atamulu Likenoid Dermatozlar ve D Vitamini Nihal Altunışık Vitiligo ve D Vitamini Ayşe Akbaş Melasma ve D Vitamini İbrahim Etem Arıca Rozase ve D Vitamini Nalan Saraç Akne ve D Vitamini Selma Korkmaz Hidradenitis Süpürativa ve D Vitamini Yılmaz Ulaş Seboreik Dermatit ve D Vitamini Dilek Başaran Otoimmün Büllöz Hastalıklar ve D Vitamini Sezgi Sarıkaya Solak Bağ Doku Hastalıkları ve D Vitamini Kevser Gök Behçet Hastalığı ve D Vitamini Şule Ketenci Ertaş, Ragıp Ertaş İdiyopatik Fotodermatozlar ve D Vitamini Bülent Nuri Kalaycı İktiyozis ve D Vitamini Tubanur Çetinarslan Epidermolizis Bülloza ve Vitamin D Eda Haşal Kseroderma Pigmentozum, Epidermodisplasia Verrusiformis ve D Vitamini Derya Yayla Nevüsler ve D Vitamini Serpil Şener, Suat Sezer Aktinik Keratoz ve Seboreik Keratozda D Vitamini Mahmut Sami Metin Deri Maliniteleri ve D Vitamini Sevda Önder Vaskülitler ve Vitamin D Havva Hilal Ayvaz Venöz Trombozis ve D Vitamini Cahit Yavuz Yara İyileşmesi ve D Vitamini Bülent Nuri Kalaycı Diyabetik Ayak Ülseri ve D Vitamini Gözde Ulutaş Demirbaş, Abdullah Demirbaş Granülomatöz Hastalıklar ve D Vitamini Selma Bakar Dertlioğlu Deri Enfeksiyonları ve Vitamin D Atıl Avcı Oral Mukoza Hastalıkları ve D Vitamini Ali İhsan Güleç Tırnak Sağlığı ve Hastalıklarında D Vitamini Hülya Cenk Alopesiler ve D Vitamini Munise Daye Hirsutizm ve D Vitamini Efşan Gürbüz Yontar Sistemik Kortikosteroid Kullanımında D Vitamini Desteği Selma Korkmaz Fototerapi ve D Vitamini Tuğba Özkök Akbulut Covıd-19 Ve Vitamin D Sibel Altunışık Toplu D Vitamini Tedavisinin Yan Etkileri ve D Vitamini Tedavisi Sürecinde Dikkat Edilecek Hususlar Dursun Türkmen, Nihal Altunışık D Vitamini Ve İlaç İlaç Etkileşimleri Şule Gökşin D Vitamini İntoksikasyonu Bedriye Müge SÖNMEZ
Topical corticosteroids have been used by dermatologists for decades for various inflammatory dermatoses. Since the advent of the corticosteroid era, we have learned a great deal of information about these topical drugs. Here, we present a chapter to further the understanding of how topical corticosteroids are used in the clinic. The pharmacology and pharmacokinetics are discussed in detail, ranging from the various potency assays to the organic chemistry of the backbone molecule and the subtle changes that affect its properties. The importance of understanding the vehicle and its implications are emphasized. Mechanisms of action are highlighted, with specific anti-inflammatory effects discussed in relation to the physiologic changes that are made in the skin. Selected clinical indications are included with respect to the evidence-based literature. Although topical corticosteroids generally act locally, their systemic adverse effects are examined with particular attention to the hypothalamic–pituitary–adrenal axis. Common local adverse effects and phenomena are covered as well as allergic contact dermatitis caused by the active molecule or components in the vehicle. Guidelines of use and recommendations for therapy of inflammatory dermatoses are suggested. The information in this chapter is supplemented by boxes and tables highlighting practical topics such as potency classes, vehicle types, topical corticosteroids that do not contain propylene glycol, and a comprehensive list of the generic and common brand names.
Medical therapies of vitiligo have a twofold aim: stopping inflammation and regenerating pigment cells. So far, the first aim has been generally fulfilled for short periods with courses of systemic corticosteroids or with only topical anti-inflammatory drugs for limited vitiligo. Maintenance treatment for long term control of microinflammation remains more problematic since this issue has not been addressed convincingly in large studies. The second aim relies mostly on phototherapies, which can also participate to the control of microinflammation. The most effective medical approaches combine anti-inflammatory and regenerative strategies. After psoriasis and atopic dermatitis, new targeted and semi targeted therapies (such as JAK inhibitors) are currently in development for vitiligo and alopecia areata.
Vitiligo treatment has to be tailored to every individual after considering several individual features, including age, gender, and ethnic skin type as well as the specific location of patches. Vitiligo affects people of all age groups though the highest incidence is seen in the second and third decades of life. Treatment options are limited in childhood vitiligo because some systemic therapies are contraindicated, phototherapy is difficult to administer, there are age-specific adverse effects of different medicines, and, finally, there are difficulties in undertaking surgical treatment in children. In spite of all these limitations, response to medical as well as surgical treatments is generally stated to be better in children compared to adults. Vitiligo in older patients does not usually produce as much distress as in young people since the psychosocial burden is considerably less at this stage of life when getting married and securing employment are not of concern. The social stigma and cosmetic disfigurement of vitiligo affect both men and women, but the burden is significantly heavier in women, particularly in communities where marriages are arranged by families. Treatment options and response are similar in men and women. Vitiligo in subjects with darker skin poses particular problems because of the greater visibility and disfigurement along with the widespread prejudices and taboos associated with the disease in these communities. The location of patches is an important determinant of response with vitiligo on the hands and feet, knees and elbows, and the mucosae responding poorly to all current treatment modalities. Choice of surgical technique, dressing, and postoperative care and instructions are guided by the site affected.
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.
In children with vitiligo, potent topical corticosteroid is the drug of choice. However, atrophy is a common side effect which should be kept in mind. Topical pimecrolimus or tacrolimus may be considered when side effects of steroids outweigh the benefits.
In adults with recent-onset vitiligo, the first line of treatment is the use of potent or super potent topical steroid for not more than 2 months. Side effects of topical steroid and abuse must be explained to the patient.
Phototherapy (PUVA) should be considered for treatment of cases unresponsive to conservative treatment.
Depigmentation with monobenzyl ether of hydroquinone is strictly meant for patients with more than 50 % depigmentation or those who have extensive depigmentation on the face or hands.
Vitiligo is an acquired cutaneous achromia characterized by depigmented macules of various shapes and sizes occurring irrespective of age, sex, and race. Vitiligo in children differs from that in adults by showing a higher incidence in females, segmental vitiligo being more common and less frequently associated with other systemic autoimmune and endocrine disorders. Childhood vitiligo deserves special attention not only because of its frequent occurrence but also being a tough challenge as regards to treatment is concerned.
There are numerous skin conditions that occur commonly in children with ethnic skin, including vitiligo, progressive macular hypomelanosis, pityriasis alba, acne keloidalis nuchae, pseudofolliculitis barbae, and keloids. Though these conditions occur in both children and adults, children may have different patterns of clinical presentation and response to therapy. In caring for such patients, important treatment considerations include side effects of systemic medications and tolerability of invasive procedures. Quality of life is an important measure and should not be compromised by either the skin disease or its treatment.
Ethnopharmacological relevance:
Vitiligo is a depigmentation disorder, which results in substantial cosmetic disfigurement and poses a detriment to patients' physical as well as mental. Now the molecular pathogenesis of vitiligo still remains unclear, which leads to a daunting challenge for vitiligo therapy in modern medicine. Herbal medicines, characterized by multi-compound and multi-target, have long been shown effective in treating vitiligo, but their molecular mechanisms of action also remain ambiguous.
Materials and methods:
Here we proposed a systems pharmacology approach using a clinically effective herb formula as a tool to detect the molecular pathogenesis of vitiligo. This study provided an integrative analysis of active chemicals, drug targets and interacting pathways of the Uygur medicine Qubaibabuqi formula for curing Vitiligo.
Results:
The results show that 56 active ingredients of Qubaibabuqi interacting with 83 therapeutic proteins were identified. And Qubaibabuqi probably participate in immunomodulation, neuromodulation and keratinocytes apoptosis inhibition in treatment of vitiligo by a synergistic/cooperative way.
Conclusions:
The drug-target network-based analysis and pathway-based analysis can provide a new approach for understanding the pathogenesis of vitiligo and uncovering the molecular mechanisms of Qubaibabuqi, which will also facilitate the application of traditional Chinese herbs in modern medicine.
Loss of pigment, whether hypopigmentation, depigmentation, or dyspigmentation, is a common complaint in pediatric patients of color. Childhood loss of pigment can be divided into localized or generalized variants, congenital (under the age of 2 years at onset) or acquired, and by etiology. The following chapter identifies strategies to identify causes of pigment loss in children and reviews specific diagnoses commonly noted and pertinent to or with nuances in children of color worldwide.
Background:
Vitamin D deficiency is associated with a number of autoimmune diseases. We completed a meta-analysis of observational studies to establish whether there was a relationship between hypovitaminosis D and the autoimmune skin disease vitiligo.
Methods:
Comprehensive search was applied in the MEDLINE and EMBASE databases from their inception to December 2015. Inclusion criteria were observational studies that assessed 25-hydroxyvitamin D (25(OH)D) levels in adults with vitiligo. The main outcome was the mean difference in serum 25(OH)D level between patients with vitiligo and controls.
Results:
Our search strategy identified 383 articles; seventeen studies met the criteria for full-length review and seven studies, containing the data of 1,200 patients, were included in a random-effects model meta-analysis. The pooled mean difference in serum 25-hydroxyvitamin D concentration between patients with vitiligo and controls was -7.45 ng/mL (95% confidence interval, -12.99 to -1.91, P-value=0.01). The between-study heterogeneity (I(2) ) was 96%, P=value<0.001.
Conclusions:
This meta-analysis identifies a significant relationship between low 25-hydroxyvitamin D levels and vitiligo, but does not prove causation. Our findings emphasize the importance of measuring 25-hydroxyvitamin D levels in patients with vitiligo. Further studies will be needed to establish whether vitamin D supplementation in this population improves the outcome of vitiligo. This article is protected by copyright. All rights reserved.
Background and purpose: Vitiligo is a common acquired pigmentation disorder. There are various therapeutic options for the treatment of vitiligo which bare some limitations due to their side effects. Recently topical immunomodulators (TIMS) such as topical Pimecrolimus have been used for the treatment of vitiligo in children as safe and efficient therapeutic options. This study compared the efficacy of the combination therapy of Pimecrolimus 1% cream and Mometasone cream with either agent alone in the treatment of childhood vitiligo. Materials and methods: In a nonrandomized double blind interventional study, 50 patients were enrolled. In each patient three lesions was selected. Topical Pimecrolimus cream 1% was applied to the first lesion twice daily, topical Mometasone furoat 0.1% ointment was applied for the second lesion every night, and Pimecrolimus cream 1% and topical Mometasone ointment 0.1% were applied to the third lesion twice/daily for the first five days. Topical Mometasone furoat 0.1% ointment was used at nights for the rest of the days of the week. All three treatments were administered simultaneously over three months. The data was analyzed using SPSS V.20. Results: Forty patients completed the study period whose mean age was 10.6 years and 46% were male. Significant decreasing trend was seen in the lesions size over time (P< 0.0001). However, this decreasing trend was not statistically significant among the three treatment groups at the end of the study (P= 0.5). Conclusion: In this study combination therapy had no any advantage to either Pimecrolimus or Mometasone. However, due to the limited number of patients in this study, further studies with large sample sizes are needed to evaluate the efficacy of this type of combination therapy and other combination therapies.
Background: Topical corticosteroids and oral psoralen plus ultraviolet A radiation (PUVA therapy) are two common treatment methods for vitiligo. The aim of this study was to compare the efficacy, complications and patterns of repigmentation of these two methods. Methods: This prospective randomized clinical trial was conducted from July 2007 to October 2008. Patients with disseminated vitiligo were divided into two groups. PUVA therapy was administered in one group and topical clobetasol was used in the other group. Results were recorded in 4 categories and therapeutic findings and complications were compared after 24 weeks. Results: Among 37 participants in the PUVA therapy group, 18 (48.6%) patients achieved marked and 14 (37.8%) patients showed good repigmentation. Similarly, among 35 participants in the clobetasol group, 6 (17.1%) patients showed marked and 8 (22.8%) patients showed good repigmentation. treatment complications were observed in 16.2% of the participants in PUVA group and 28.6% of the participants in clobetasol group. The patterns of repigmentation were different in the two groups. Conclusion: PUVA showed better therapeutic effects, and did not cause significant complications. Therefore, it could be used as one of the first line medications in the treatment of vitiligo.
Vitiligo is a specific, common, often heritable, acquired disorder characterized by well-circumscribed milky-white cutaneous macules devoid of identifiable functional melanocytes because of multifactorial and overlapping pathogenic mechanisms. The basic defect in vitiligo is loss of melanocytes. Narrowband ultraviolet B (NB-UVB) is an emerging, effective and safe therapy for vitiligo. Because of defective calcium homeostasis in depigmented skin, the vitamin D-3 analogs (calcipotriol and taclacitol) have been used topically in vitiligo, where modulation of the local immune response on specific T cell activation occurs. A new topical product containing a combination of vegetal catalase (CAT) and superoxide dismutase (SOD) has been used in vitiligo. In vitro studies demonstrated the capacity of this complex to dramatically reduce the production of free radicals in vitiligo cell and even to restore a normal level of melanin in melanocytes of vitiligo. Patients and Methods: The current study comprised a total of 40 patients with different clinical varieties of vitiligo. They were recruited from the Outpatient Clinic of Dermatology and Venereology Department, Tanta University Hospitals. The studied patients were divided into: G1: Included 20 patients subjected to topical combination of calcipotriol plus betamethazone dipropionate ointment with NB-UVB on the left side of the patient and NB-UVB alone on the right side of the same patient. G2: Included 20 patients subjected to topical SOD/CAT gel with NB-UVB on the left side of the patient and NB-UVB alone on the right side of the same patient. Results: Comparison in the response of the treatment in GI and GII between right and left side revealed no statistically significant difference between the two sides. Comparison in the response in the left side in G I and G II showed no statistically significant difference in repigmentation between the two groups. There were no significant correlation between the results of the combination treatment plus NB-UVB in both groups and clinical criteria of vitiligo patients. There were statistically significant differences between distribution of sites of the lesions in vitiligo patients and treatment with topical applications plus NB-UVB regarding response of the treatment in the face and neck in G II. While in G I the face had excellent response but not statistically significant. Conclusions: The current study had shown that NB-UVB treatment alone is a moderately effective treatment for vitiligo. Betamethasone dipropionate/calcipotriol, when used in combination with NB-UVB were found to be superior in efficacy than NB-UVB alone, but the results were not statistically significant, while SOS/CAT gel does not appear to add any incremental benefit to NB-UVB alone. It could be recommended that further studies should be performed on this subject.
› Vitiligo, an autoimmune disorder that targets melanocytes, is difficult to treat.
› At present, the best monotherapeutic option is narrowband ultraviolet B phototherapy.
› Most of the regimens that show reasonable efficacy in the treatment of vitiligo are either phototherapeutic regimens or combination therapies that include phototherapy.
The idea that Vitamin D analogues may be considered an option for the treatment of the vitiligo arises from the casual observation of the occurrence of cutaneous perilesional hyperpigmentation after their application on psoriatic plaques together with phototherapy [6, 14, 23, 27, 28]. Starting from this clinical evidence, several in vitro and in vivo data support the therapeutic role of calcipotriol and tacalcitol for vitiligo (Table 3.2.3.1). Skin cells, including keratinocytes, melanocytes, and dermal fibroblasts possess Vitamin D receptors (VDR), the activation of which induces several genes associated with proliferation and differentiation, and with the inflammatory reaction. Exposure of human melano-cytes to Vitamin D promotes tyrosinase activity and melanogenesis, together with the up-regulation of c-Kit as well as morphological modifications, mainly increases the number and length of the dendrites. With regard to keratinocytes, Vitamin D produces differentiation, decreased proliferation, and the release of the proinflammatory cytokines IL-8 and IL-6, and increased production of IL-10. In vitiligo skin, both melanocytes and keratinocytes have been shown to possess an alteration of the Ca++ uptake and a decreased intracellular concentration of the ion, which could compromise the melanogenesis by increasing the level of reduced thi-oredoxin, which inhibits tyrosinase [6].
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.
In an unprecedented effort in the field of vitiligo, a global consensus resulted on a suggested new classification protocol for the disease. The main histopathological finding in vitiligo is the total absence of functioning melanocytes in the lesions, while the inflammatory cells most commonly found on the edges of the lesions are CD4+ and CD8+ T lymphocytes. Physical and pharmacological treatment strategies aim to control the autoimmune damage and stimulate melanocyte migration from the unaffected edges of lesions and the outer hair follicle root sheath to the affected skin; moreover, surgical treatments can be combined with topical and physical treatments.
Vitiligo is a common depigmenting disease that can affect the skin and mucosal surfaces. Various treatments have been used over the years with varying repigmentation rates. This review looks at the evidence of commonly used therapies for vitiligo.
© 2014 The Australasian College of Dermatologists.
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.
Background:
Vitiligo is a common disorder of depigmentation that has been associated with other autoimmune diseases. No recent large-scale data exist on the rates of comorbidities associated with vitiligo from the United States population.
Objectives:
To identify the prevalence of comorbidities as well as associated laboratory abnormalities in vitiligo patients.
Methods:
All medical records dating from January 1, 2000 to June 21, 2011 within the Research Patient Data Repository were evaluated retrospectively using a novel artificial intelligence-based computer program. A total of 3,280 patients carrying the diagnosis of vitiligo were identified using ICD-9 code 709.01. We randomly selected 300 patients and validated the diagnosis by manually reviewing their medical records. These results were used to create a model that was then applied to the larger set yielding 2,441 true vitiligo patients. 1,657 (68%) were diagnosed by dermatologists and 784 (32%) by non-dermatologists. We identified the prevalence of other comorbid autoimmune conditions by searching problem lists of vitiligo patients and collected laboratory data from the first available data point in the system for each patient.
Results:
Women were more frequently represented (57.6%) than men (42.4%). The majority of vitiligo patients were White/Caucasian (56.9%), followed by Hispanic/Latino (19.4%). 565 (23%) had one of the following comorbidities: 287 thyroid-related, 186 psoriasis, 72 rheumatoid arthritis, 59 alopecia areata, 55 inflammatory bowel disease, 53 systemic lupus and 20 type I diabetes mellitus. 41% had elevated anti-nuclear antibody levels. Almost half of the patients tested had elevated thyroid peroxidase antibodies. Over 50% of the patients tested had low or insufficient levels of 25-OH vitamin D.
Conclusion:
We found a high prevalence of comorbidities among individuals with vitiligo presenting to teaching hospitals in Boston, Mass. Comorbid autoimmune conditions were seen in 23% of vitiligo patients, thyroid disorders and psoriasis being the most common. Screening for these conditions, especially thyroid disorders, should be considered in vitiligo patients.
Childhood vitiligo differs from the adults by showing a higher incidence in females, segmental vitiligo being more common and less frequent association with other systemic autoimmune and endocrine disorders. Childhood vitiligo is often associated with a marked psychosocial and long lasting effect on the self-esteem of the affected children and their parents, hence an adequate treatment is very essential. Treatment of vitiligo is indeed a tough challenge for the dermatologists' more so in the background of childhood vitiligo. Although multiple therapeutic modalities are available in the therapeutic armamentarium, not all can be used in children. This brief report updates regarding various therapies available in the treatment of childhood vitiligo.
Vitiligo can be treated using traditional, new and experimental therapies, and newly available treatments can be divided into medical, physical and surgical types. Medical treatments include topical corticosteroids and other topical treatments, such as antioxidants, tacrolimus and pimecrolimus, prostaglandin E and vitamin D derivates. Physical therapies include narrow-band UVB light (NB-UVB), NB-UVB microphototherapy, NB-UVB excimer laser and monochromatic excimer light. All can be safely used in children. NB-UVB is recommended for generalized vitiligo, while the others are indicated in patients affected by segmental and bilateral symmetrical vitiligo with a cutaneous involvement of less than 20%. They enable drastic reduction of the total dose of radiation, even though they preserve a potential long-term carcinogenic risk that has to be considered in this type of patient. Surgical therapies are reserved for adolescent or adult patients with a stable vitiligo.
Introduction:
Vitiligo is a common pigmentary skin disorder, characterized by the appearance of white macules on the skin, mucosal or hair. Treatment is often a tough challenge and involves a wide range of therapies.
Areas covered:
This review focuses on available first- and second-line pharmacological treatments for vitiligo. In particular, the mechanisms of action, the main indications, the efficacy and the most important side effects are reviewed. Moreover, a brief discussion is provided, regarding other nonpharmacological treatments, such as phototherapy and surgical options, due to their importance and successful outcomes in vitiligo treatment. Finally, a concise overview regarding the future directions in vitiligo therapy is presented.
Expert opinion:
The promising outcomes reported here demonstrate that it is possible to achieve a satisfactory and often stable repigmentation of vitiligo lesions. Topical corticosteroids, calcineurin inhibitors, phototherapy and photochemotherapy represent the first-line therapeutic options, due to their safety and efficacy, whereas vitamin D analogues, targeted phototherapy, oral corticosteroids and surgery should be used as second-line therapies. Other therapies, such as antioxidants, can be used in association with other therapeutic options, whereas depigmenting agents should be used only in cases of extensive vitiligo, recalcitrant to other treatments.
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.
Vitiligo is a common skin disorder that results in depigmentation. With the appropriate management, many patients can minimize disease progression, attain repigmentation, and achieve cosmetically pleasing results. There are numerous medical and surgical treatments aimed at repigmentation; therapies for depigmentation are available for patients with recalcitrant or advanced disease. The use of cosmetics at all stages of treatment may be vital to the patient's quality of life. Understanding all the available options helps choose the appropriate treatment plan and tailor it to your patient. Part II of this two-part series on vitiligo discusses the indications for, evidence behind, and adverse effects associated with many of the therapies used for vitiligo. Both conventional medical and surgical options are discussed in addition to several alternative and promising new therapies.
Currently many children and adolescents with vitiligo fail to respond to traditional medical treatment. However, their parents want the lesion to be removed as soon as possible. Although surgical therapies are viable alternatives in refractory and stabilized vitiligo, there are rare reports on surgical therapies for childhood vitiligo.
To assess the effectiveness and feasibility of using suction blister epidermal grafting for small-sized childhood vitiligo.
Twenty children with small-sized lesions of stable vitiligo were treated using epidermal grafts and followed-up for 6-12 months.
After 6-12 months of follow-up, treatment outcomes were excellent in 17 patients (85%), good in two patients (10%), and poor in one patient (5%), out of a total of 20 patients. The mean repigmentation rate was 88.55%. The location of the lesions was probably a factor in determining the outcomes of transplantation. No scar formation or other complications were observed in any patients.
Suction blister autologous epidermal grafting is a rapid, safe, and effective treatment for stable childhood vitiligo, especially in refractory and stable children with small-sized lesions.
This review addresses recent changes in the understanding and the treatment of vitiligo vulgaris.
Two target genes for vitiligo have been identified, NACHT-leucine-rich-repeat protein-1 (NALP1), part of the inflammasome cascade, and tyrosinase, the enzyme that produces melanin. Identification of reactive oxidation species has furthered the understanding of melanocyte destruction. Comorbid autoimmune disease, including thyroid autoimmunity seen in 25%, is genetically linked to generalized vitiligo and is noted in both childhood vitiligo patients and their families. Screening for vitamin deficiencies and concurrent autoimmunity can be beneficial to the overall health of the child with vitiligo. About half of all vitiligo vulgaris patients have onset of their illness during childhood, causing increased psychological stress during the formative years. Fortunately, therapy has improved as well, with the development of newer topical agents for vitiligo, including topical calcineurin inhibitors; new topical combinations such as topical corticosteroids and calcipotriene; and new technological advances including narrowband ultraviolet B and excimer laser.
A cyclic approach to therapy should be used wherein topical agents are altered every 6-8 months and technology is used as an alternative after achievement of maximal topical response. With cyclic therapy and early disease intervention, good cosmetic outcomes may be achievable, particularly in localized cases.
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.
Topical vitamin D analogues have been reported to be an effective treatment in patients with psoriasis. Comparative studies with existing treatments are required.
Our purpose was to compare the effectiveness of calcipotriol (50 micrograms/gm) and betamethasone 17-valerate (1 mg/gm) ointments twice daily in the treatment of stable plaque psoriasis.
This study was a randomized, double-blind comparison over 6 weeks in 409 patients. Efficacy, as measured by the Psoriasis Area and Severity Index (PASI), and safety were assessed at 2, 4, and 6 weeks.
Reduction of PASI was statistically significant at all time points for both treatments but there were no significant between-treatment differences. At the completion of 6 weeks of treatment, the mean PASI reduction was 5.50 for calcipotriol and 5.32 for betamethasone (95% confidence interval [CI] -0.40 to 0.78). Analysis of patient assessment at 6 weeks showed clearance or marked improvement in 61.2% of the calcipotriol patients and 50.5% with betamethasone (95% CI 1.4 to 20.8). Calcipotriol produced significantly more local side effects (19.5% compared with 3.9%, p less than 0.001); however, these were minimal leading to withdrawal in only 3 of 205 patients.
Calcipotriol ointment was as effective as betamethasone 17-valerate ointment as measured by the PASI and superior as measured by self-assessment in patients with stable plaque psoriasis. Both treatments were well tolerated.
We found an increased amount of immunoreactive tyrosinase in human melanocytes after 6-d culturing with vitamin D3 (cholecalciferol). Most of these melanocytes became more dendritic and swollen in a fashion similar to that noted in the skin after ultraviolet irradiation. However, 7-dehydrocholesterol (pro-vitamin D3) or 1 alpha,25-dihydroxy-vitamin D3 (activated vitamin D3) were found to have little effect on the same system. Because vitamin D3 is known to be photochemically converted from pro-vitamin D3 in the skin by ultraviolet irradiation, the mechanism of human skin pigmentation after ultraviolet irradiation, thus far unknown, may be at least partly explained by this stimulating effect of vitamin D3 on melanocytes.
Four human melanoma cell lines were examined for their responsiveness to the hormones 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), calcitonin, and parathyroid hormone (1-34). Cells from each of the 4 lines contained high affinity binding sites for 1,25(OH)2D3. At high cell densities, binding of 1,25(OH)2D3 was diminished due to a decrease in receptor number with no apparent change in affinity. Preincubation with 1,25(OH)2D3 (10(-10) to 10(-8) M) increased tyrosinase activity 1.3- to 3.2-fold and 25-hydroxyvitamin D3-24-hydroxylase activity 1.4- to 10-fold. Human calcitonin (0.82 to 82.5 ng/well) raised the intracellular concentration of cyclic adenosine monophosphate 1.4- to 9.4-fold. Tyrosinase activity increased in response to calcitonin in 2 of the cell lines, decreased in the third, and showed no change in the fourth. Human parathyroid hormone (1-34) in concentrations of 1 to 10 ng/ml produced no significant changes in cyclic adenosine monophosphate accumulation, cell numbers, or tyrosinase activity in any of the cell lines. This study indicates that the phenotype of human melanoma cells can be modulated by the calciotropic hormones 1,25(OH)2D3 and calcitonin.
Melanin synthesis of B16 mouse melanoma cells was found to be stimulated dose and time dependently by 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the hormonal form of vitamin D3. The stimulation of melanogenesis resulted from an increase in the activity of tyrosinase, a key enzyme in melanin synthesis. The minimum dose required for this stimulation was as low as 0.05 ng/ml, or 0.12 nM, a physiological level of plasma 1 alpha,25(OH)2D3. The stimulation by 1 alpha,25(OH)2D3 was specific; other derivatives of vitamin D3 caused no stimulation at a concentration of 500 ng/ml. When the cells were plated on agar plates, the proportion of dark or black colonies was not increased by the exposure to 1 alpha,25(OH)2D3. Furthermore, this compound did not induce melanin synthesis of an amelanotic variant. Thus, its stimulatory effect seemed to be due to stimulation of melanin synthesis of melanotic cells, rather than to conversion of amelanotic clones to melanotic ones. 1 alpha,25(OH)2D3 did not induce intracellular cyclic adenosine 3':5'-monophosphate, while cholera toxin induced cyclic adenosine 3':5'-monophosphate and stimulated melanin synthesis and tyrosinase activity much more than did 1 alpha,25(OH)2D3, suggesting that 1 alpha,25(OH)2D3 stimulates melanin synthesis by a cyclic adenosine 3':5'-monophosphate-independent mechanism. B16 melanoma cells contained specific receptors for 1 alpha,25(OH)2D3. Scatchard plot analysis revealed two types of receptor; the high-affinity receptor had a Kd of 18.3 pM and an Nmax of 10.6 fmol/mg of protein. The specificity of receptor binding was demonstrated by studies showing that, for 50% displacement of 1 alpha,alpha,25(OH)2D3 binding, other derivatives were required at 500 times higher concentrations or more. In contrast to 1 alpha,25(OH)2D3, retinoic acid inhibited melanin synthesis and tyrosinase activity of B16 melanoma cells dose and time dependently. On simultaneous treatment, 1 alpha,25(OH)2D3 and retinoic acid caused mutual interference, and a balance between their respective stimulating and inhibitory effects was obtained at a molar ratio of 10:1; i.e., with 10 nM 1 alpha,25(OH)2D3 and 1 nM retinoic acid.
45Ca2+ has been used to measure kinetics for the uptake, efflux, and "steady state" of this regulatory cation in keratinocytes grown from the involved and uninvolved skin of one donor (JM) with vitiligo. Cells grown from uninvolved skin yielded a very rapid uptake and efflux of this isotope before reaching "steady state". A similar profile has been found for keratinocytes from normal healthy adult controls. However, cells established from vitiliginous skin showed a slow uptake of 45Ca2+ before reaching the same "steady state" as the controls. 45Ca2+ efflux has not been observed in vitiliginous keratinocytes. Furthermore, vitiliginous keratinocytes yielded a higher concentration of extracellular bound 45Ca2+ compared with keratinocytes from uninvolved skin. Since Ca2+ has been found to be an allosteric inhibitor of membrane-associated thioredoxin reductase, this defect in Ca2+ transport may explain the proposed breakdown in free radical defense in vitiligo. These findings may also shed more light on the etiology of this disorder.
Calcipotriol is a synthetic analogue of vitamin D, used in the treatment of psoriasis. Until now no specific sid-effects have been described after combined therapy with calcipotriol and UV. We describe 3 patients, who in the summer of 1993, after a combined treatment of calcipotriol and heliotherapy, developed hyperpigmentation in the site where the ointment had been applied. Hyperpigmentation healed spontaneously in less than 7 months. To the best of our knowledge there are no other reports of this side-effect due to calcipotriol. In our opinion the fact that the 3 patients presented the hyperpigmentation only on the treated lesions and that, in the past, they had not presented similar lesions after exposure to sunlight confirms the relationship between the hyperpigmentation and the combined treatment used.
Melanocytes were successfully established from involved and uninvolved skin of a patient with acute acrofacial vitiligo. Cells from involved epidermis showed a fivefold decrease in the rate of radiolabelled 45Ca uptake compared with uninvolved and control cells. These results are similar to previous findings in keratinocytes from involved skin in patients with vitiligo. Since 6-biopterin is cytotoxic to melanocytes and calcium controls the redox status of the 6-biopterin/(6R)5, 6, 7, 8-tetrahydrobiopterin equilibrium via the thioredoxin reductase/thioredoxin system, these results underline the importance of this electron transfer system for both melanocyte function and survival.
The biologically active vitamin D analog calcipotriol is effective and safe in the topical treatment of psoriasis, but its exact mechanism of action is unknown.
We investigated expression of 1,25-dihydroxyvitamin D3 receptors, markers for inflammation (CD1a, CD4, CD8, CD11b, CD15; NAP-1/interleukin-8; 55 kd tumor necrosis factor-receptor; intercellular adhesion molecule-1; HLA-DR), proliferation (proliferating cell nuclear antigen, Ki-67), and differentiation (transglutaminase K; involucrin; cytokeratin 16) in psoriatic skin during topical calcipotriol treatment.
For immunohistochemical staining we used the labeled avidin-biotin technique on cryostat-cut sections.
We found a significant increase of 1,25-dihydroxyvitamin D3 receptor expression in epidermal basal keratinocytes of lesional psoriatic skin during calcipotriol treatment. In all patients analyzed, effects on proliferation and differentiation of epidermal keratinocytes were stronger than effects on dermal inflammation. Effects on inflammation were more pronounced in the epidermal than in the dermal compartment.
Our findings indicate that analogs of 1,25-dihydroxyvitamin D3 upregulate their corresponding receptor in human keratinocytes in vivo. This mechanism may be important in the therapeutic efficacy of vitamin D analogs in psoriasis. The differential therapeutic effects in the epidermal and dermal skin compartments may be due to a reduced bioavailability of calcipotriol in the dermal compartment.
Calcipotriene is often used with UVB or PUVA, but interactions between UV radiation and calcipotriene have not been examined extensively.
Our purpose was to examine interactions between calcipotriene and UV light.
Minimal erythema doses (MEDs) were determined with UVB and immediate pigment darkening was measured for UVA. The effect of calcipotriene ointment applied before phototesting was examined. Thick and thin applications of calcipotrience were compared. Calcipotriene ointment was applied to a small area on the skin before phototherapy. Patients received either UVB, PUVA, UVA, or no phototherapy. After phototherapy, the ointment was collected and assayed by reverse-phase, high-performance liquid chromatography.
MEDs for UVB and immediate pigment darkening for UVA were unaffected by calcipotriene. Thick application of calcipotriene, however, increased the MED, UVA caused substantial reductions in the concentration of detectable calcipotriene.
When used in conjunction with PUVA, calcipotriene should be applied after exposure to UVA.
Calcipotriol/calcipotriene (Dovonex/Daivonex) ointment plus phototherapy has been used in the treatment of psoriasis.
We will attempt to clarify two issues: First, is there any benefit to combining the above treatment modalities? Second, is there any increased risk associated with the use of the combination?
A complete review of the literature revealed four studies dealing with the combination of calcipotriol with UVB phototherapy and three studies dealing with the combination of calcipotriol with PUVA phototherapy.
These studies showed an advantage to the use of the combination compared with the use of either treatment alone.
Topical calcipotriol enhances the effect of UVB and PUVA phototherapy.
Side effects of topical corticosteroids limit their long-term use. Calcipotriene/calcipotriol (Dovonex/Daivonex) ointment is not associated with any of the side effects of corticosteroids and has been shown to thicken the skin in contrast to the cutaneous atrophy caused by topical steroids.
We attempted to determine whether the addition of calcipotriene to a regimen of topical steroids results in an improved benefit/risk ratio.
Published and unpublished data on combination regimens were reviewed.
In long-term regimens for psoriasis, substituting calcipotriene for topical corticosteroids may result in a steroid-sparing effect. Conversely, topical corticosteroids may suppress the development of local cutaneous irritation that occurs in patients treated with calcipotriene ointment.
Psoriasis regimens combining calcipotriene ointment with superpotent steroids such as halobetasol ointment can result in greater improvement and fewer side effects.
Most biologically active forms of vitamin D3 (1,25(OH)2D3) and its analogs have functions and therapeutic potential that extend beyond those of regulating bone mineralization and intestinal calcium transport.
We attempt to provide the rationale for the effectiveness of 1,25(OH)2D3 and its analogs in dermatology.
The recent literature on the mechanisms of action of 1,25(OH)2D3 were reviewed.
1,25(OH)2D3 affects keratinocyte differentiation partly through its regulation of epidermal responsiveness to calcium. Calcium and 1,25(OH)2D3 interact in transcription of the genes required for differentiation and in the stability of the mRNAs produced from such genes.
An understanding of these mechanisms provides a rationale for treatment of various skin diseases with 1,25(OH)2D3 and its analogs and directs development of more effective therapy.
The destruction of melanocytes is the cause of depigmented maculae that clinically represent the disease vitiligo. Although the cause is unknown, various theories such as the autoimmune, autocytotoxic, and neural hypotheses have been proposed. Extensive research has provided numerous answers regarding the pathogenesis, histopathologic evidence, and treatment of vitiligo. This discussion of vitiligo summarizes the varied clinical presentations of the disease, theories attempting to explain the mechanism of melanocyte destruction, histopathologic findings, and different treatment modalities currently available.
A large variety of therapeutic agents are being tried for the treatment of vitiligo, but psoralens continue to be mainstay of treatment although they are not uniformly effective. Recent advances in pathophysiology have established a perturbed calcium homeostasis in affected skin, and melanocytes were shown to express vitamin D3 receptors.
The purpose of present study was to determine the efficacy of the combination of PUVAsol with topical calcipotriol in the treatment of vitiligo.
Nineteen patients with essentially bilateral symmetrical lesions were enrolled in a randomized, double-blind, right/left comparative study of 18 months duration. An oral dose of 0.6 mg/kg 8-methoxypsoralen was given 2 h before exposure to sunlight thrice weekly to all patients. The patients were advised to apply calcipotriol (50 microgram/g) on one side of the body and placebo ointment over the lesions on the other side twice daily.
At the end of 6 months, 12 patients (70%) showed marked to complete improvement on calcipotriol-treated sides as compared to 6 patients (35%) showing similar improvement on placebo-treated sides (p <0.05). At the end of treatment, 13 patients (76%) showed marked improvement in calcipotriol-treated lesions whereas 9 patients (53%) showed moderate to marked improvement in placebo-treated lesions. The repigmentation of hands and feet was much better with the combination of PUVAsol and calcipotriol.
The combination of PUVA and calcipotriol is highly effective and works faster and may be used for shortening the therapy with PUVA in the treatment of vitiligo.
The vitamin D3 analogue calcipotriol (calcipotriene) is an effective topical treatment for psoriasis. In combination with other antipsoriatic agents, such as ultraviolet radiation, calcipotriol is reported to improve the overall efficacy of the treatment. Here we describe two patients treated with a combination treatment of calcipotriol and bath psoralens and ultraviolet A who developed hyperpigmentation at the lesional sites where calcipotriol ointment was applied.
A large variety of therapeutic agents have been tried for the treatment of vitiligo, but psoralens continue to be the main treatment. Twenty-one patients age 5 to 17 years with vitiligo were enrolled in this study. The children were advised to apply calcipotriol 50 microg/g in the evening and expose themselves to sunlight the next day for 10 to 15 minutes. The patients were followed at 3-week intervals. Initial repigmentation occurred in the majority of children after 6 to 12 weeks of treatment. Marked to complete repigmentation was seen in 10 of 18 patients. Four patients showed moderate improvement while the remaining four patients showed minimal or no improvement. No patient developed new lesions. The repigmentation was cosmetically excellent in the majority of children. All patients tolerated the calcipotriol well except for three patients who complained of mild irritation on application. All of the laboratory investigations, including serum calcium levels remained normal. The rationale for this study originated from recent advances in the understanding of vitiligo at the molecular level. Furthermore, development of hyperpigmentation in patients with psoriasis receiving treatment with PUVA and calcipotriol has been observed. Our results are encouraging and offer a new and potentially efficacious treatment for this pigmentation disorder in children.
PUVA therapy remains a primary treatment for vitiligo, despite unsatisfactory results. Because of calcipotriol's reported effects on melanocytes and on immunomodulatory and inflammatory mediators we wondered whether adding calcipotriol to PUVA would be more effective than PUVA alone in treating vitiligo.
We sought to determine whether the combination of topical calcipotriol and PUVA therapy increases the responsiveness of patients with vitiligo refractory to PUVA alone.
Twenty-one patients with vitiligo refractory to previous PUVA therapy were studied. Patients received 60 sessions of PUVA 3 times a week and 0.005% topical calcipotriol twice daily. Patients were monitored for repigmentation overall and on the trunk, extremities, and acral regions.
Starting at the median of the 17th treatment session, some degree of repigmentation was observed in 71.5% of the patients. After treatment, cosmetically acceptable overall repigmentation was observed in 29% of patients; repigmentation of lesions on the trunk, extremities, and acral region was noted in 36%, 58%, and 0% of patients, respectively. Adverse reactions were mild and tolerable.
The combination of PUVA and calcipotriol may be effective therapy and should be further investigated for the treatment of vitiligo.
The incidence and mortality rates of melanoma have risen for many decades in the United States. Increased exposure to ultraviolet (UV) radiation is generally considered to be responsible. Sunburns, a measure of excess sun exposure, have been identified as a risk factor for the development of melanoma. Because sunburns are primarily due to UVB (280-320 nm) radiation, UVB has been implicated as a potential contributing factor to the pathogenesis of melanoma. The adverse role of UVA (320-400 nm) in this regard is less well studied, and currently there is a great deal of controversy regarding the relationship between UVA exposure and the development of melanoma. This article reviews evidence in the English-language literature that surrounds the controversy concerning a possible role for UVA in the origin of melanoma. Our search found that UVA causes DNA damage via photosensitized reactions that result in the production of oxygen radical species. UVA can induce mutations in various cultured cell lines. Furthermore, in two animal models, the hybrid Xiphophorus fish and the opossum (Mondelphis domestica), melanomas and melanoma precursors can be induced with UVA. UVA radiation has been reported to produce immunosuppression in laboratory animals and in humans. Some epidemiologic studies have reported an increase in melanomas in users of sunbeds and sunscreens and in patients exposed to psoralen and UVA (PUVA) therapy. There is basic scientific evidence of the harmful effects of UVA on DNA, cells and animals. Collectively, these data suggest a potential role for UVA in the pathogenesis of melanoma. To date evidence from epidemiologic studies and clinical observations are inconclusive but seem to be consistent with this hypothesis. Additional research on the possible role of UVA in the pathogenesis of melanoma is required.
Recent advances in the pathophysiology of vitiligo have demonstrated defective calcium homeostasis in depigmented skin. 1,25-Dihydroxyvitamin D3 may be involved in the regulation of melanin synthesis, and receptors for 1,25-dihydroxyvitamin D3 have been demonstrated on melanocytes.
We conducted an open study to determine the efficacy and tolerability of calcipotriol cream as monotherapy and in conjunction with psoralen plus ultraviolet A (PUVA) in the treatment of vitiligo.
Twenty-six patients with vitiligo affecting 5-40% of their skin were recruited. Twenty-two were treated with twice-daily topical calcipotriol monotherapy (50 microg g(-1)) and four were placed on combination treatment with twice-daily topical calcipotriol 50 microg g(-1) in conjunction with topical or oral 8-methoxypsoralen PUVA three times weekly.
Treatment was well tolerated at all sites and no adverse effects were reported. After a therapy time of 3-9 months (mean 6 months), 77% (17 of 22) of those treated with monotherapy showed 30-100% improvement, and three of the four patients on combination treatment showed good response.
Topical calcipotriol appears to be an effective and well-tolerated treatment for vitiligo and can be safely used in conjunction with PUVA, but controlled studies are necessary to exclude the possibility of spontaneous repigmentation.
Encouraging results of previous uncontrolled trials suggest that calcipotriol may potentiate the efficacy of psoralen plus ultraviolet (UV) A (PUVA) therapy in patients with vitiligo.
We performed a placebo-controlled double-blind study to investigate whether the effectiveness of PUVA treatment could be enhanced by combination with topical calcipotriol in the treatment of vitiligo.
Thirty-five patients with generalized vitiligo enrolled in the study. Symmetrical lesions of similar dimensions and with no spontaneous repigmentation on arms, legs or trunk were selected as reference lesions. In this randomized left-right comparison study, calcipotriol 0.05 mg g(-1) cream or placebo was applied to the reference lesions 1 h before PUVA treatment (oral 8-methoxypsoralen and conventional UVA units) twice weekly. Patients were examined at weekly intervals. The mean number of sessions and the cumulative UVA dosage for initial and complete repigmentation were calculated.
Twenty-seven patients (nine women, 18 men; mean +/- SEM age 29.8 +/- 13.5 years) were evaluated. The mean +/- SEM cumulative UVA dose and number of UVA exposures for initial repigmentation were 52.52 +/- 6.10 J cm(-2) and 9.33 +/- 0.65 on the calcipotriol side, and 78.20 +/- 7.88 J cm(-2) and 12.00 +/- 0.81 on the placebo side, respectively (P < 0.001). For complete repigmentation, respective values were 232.79 +/- 14.97 J cm(-2) and 27.40 +/- 1.47 on the calcipotriol side and 259.93 +/- 13.71 J cm(-2) and 30.07 +/- 1.34 on the placebo side (P = 0.001). Treatment with calcipotriol and PUVA resulted in significantly higher percentages of repigmentation for both initial (81%) and complete pigmentation (63%), compared with placebo and PUVA (7% and 15%, respectively).
Our results have shown that concurrent topical calcipotriol potentiates the efficacy of PUVA in the treatment of vitiligo, and that this combination achieves earlier pigmentation with a lower total UVA dosage.
Chemistry and pharmacology of calcipotriol Vitamin D in dermatology
- A-M Kissmeyer
- Calverley Mj
- Benderup
Kissmeyer A-M, Calverley MJ, Benderup L. Chemistry and pharmacology of calcipotriol. In: Kragballe K, ed. Vitamin D in dermatology. New York: Marcel Dekker 2000;169–183.
Modulation of immuno-cytes by vitamin D Vitamin D in dermatology
- L Skov
- O Baadsgaard
- Hansen
- Er
Skov L, Baadsgaard O, Hansen ER. Modulation of immuno-cytes by vitamin D. In: Kragballe K, ed. Vitamin D in dermatology. New York: Marcel Dekker 2000;133–141.
Effect of vitamin D on Langerhans cells
- Tn Dam
Dam TN. Effect of vitamin D on Langerhans cells. In: Kragballe K, ed. Vitamin D in dermatology. New York: Marcel Dekker 2000;143–156.
Vitamin D: a calciotropic hormone regulating calcium‐induced keratinocyte differentiation
- Bilke DD