Spontaneous Repigmentation Research Articles

A review of the vitiligo literature to standardize the expression of disease severity

Abstract The literature on vitiligo is extremely heterogeneous with limited standardization in vitiligo disease severity reporting. The IDEOM Vitiligo Workgroup initiated a project to develop an improved understanding of clinical reporting of vitiligo severity and extent. A medical librarian-developed literature review identified 51 English-language clinical trials treating vitiligo topically using topical corticosteroids or topical tacrolimus that included adult and paediatric patients, with 10 or more patients. Grading of studies was performed using SORT criteria. The grading systems used included three studies reporting overall improvement: one as absolute Improvement vs. did not improve (B2), one as marked improvement (C3) and one as improvement, no change or worse (A2). Severity was reported as straight body surface area scoring (BSA) in five trials with grades of (A1, A1, B1, C2 and C3), and two via photography and mapping (A1, A2). Many studies report success as meeting the metric of 50% improvement or clearance (C3). Kanwar et al. further subdivides this into 50% to <75% or >75% (C3). Three studies add the complete clearance metric (A1, A1, B1), with some adding worsening categories. Most studies create a grading system including G0- no change (A1, A1, A2, A2< B2, B2, B3, B3), G1- 1–25%, G2- 26–50%, G3- 51–75%, G4- 75–99% (one study by Lepe et al. reports this as >75%) and G5- 100% re-pigmentation [Bae et al. (C2) report these numbers as 0, 1–24%, 25–49%, 50–74%, 75–99%, 100%]. Variations in response include the meta-analysis by Lee et al. reporting >25%, >50% and >75% re-pigmentation and the combination of G0 and G1 as < or = 25% re-pigmentation, considered a failure (A1, A1, A2. B2, C3, C3, C3). Koopmans-VanDorp (B2) and Kandil (B2) break down re-pigmentation as none, beginning (<25%), good (25–90%) or complete or almost complete (90–100%) or spontaneous re-pigmentation. Success can be defined as G3–G5 or G4–G5. Kathuria classifies <50% as failure (A1). Hu and Farajzadeh (A2) classify >50% as success, Bae (C2) classifies >75% and Kumari (B2) as >90% improvement. Majid further subdivides the score into six subdivisions (A1). Abd-Elazim (A2) reports VASI and Baldo reports DLQI. Sach (C1) and Batchelor (A1) use the vitiligo noticeability scale Baldo, with target patches reported as ‘a lot less noticeable’ or ‘no longer noticeable’ being successful. Ibrahim (A2) uses Patient-Expressed Satisfaction, reporting ‘not satisfied’, ‘slightly satisfied’, ‘satisfied’ or ‘very satisfied’. Batchelor (A1) report percentage re-pigmentation, onset and maintenance of response, treatment burden, QoL, side effects and cost-effectiveness. Body surface area total and quartiles of improvement are the most commonly reported metrics in studies with high-level evidence. The addition of categories of no improvement, complete clearance, spontaneous improvement and worsening appears to enhance information collection. Collection of data using photographs or computer-assisted BSA monitoring enhances data reproducibility. Using 50%, 75% and 90% as thresholds for success appears to be standardized, with a rarer inclusion of 100%. Validated scores like VASI represent a validated alternative collection method, which can be modified to address the 50%, 75% and 90% thresholds. Quality of life has not per se been correlated to clinical response to topical therapeutics, and current scores including patient expression of satisfaction, vitiligo noticeability and satisfaction are not known to reflect topical response at this time.

815 Translational Research in Skin of Color Spontaneous Repigmentation of Post-Chemical Burn Leucoderma

IntroductionAfter facial burn injuries to skin of color (SOC) patients, repigmentation plays a critical role in post-burn quality of life, given the acquired contrast between preserved skin and achromic scars, and that daily concealment may be difficult. While leucoderma is a well-known side-effect of deep chemabrasion with phenol, phenol-croton oil, and high concentration trichloroacetic acid, mechanisms of repigmentation are still not fully understood, and the observation of spontaneous repigmentation of a deep chemical injury in SOC has not previously been described in the literature. In our study, we present the dynamics of long-term spontaneous facial repigmentation of a Fitzpatrick V chemical burn patient, with microscopic findings of a deep chemical peel SOC animal model.MethodsWe demonstrate spontaneous repigmentation in a 37-year-old female who initially presented with depigmented areas, erosions and eschars on the face, 7 days after accidental deep chemical burn, due to self-application of 70% glycolic acid to improve acne. This is juxtaposed with a SOC porcine experiment, performed with 35% phenol, 1.6% croton-oil, to evaluate depth-of-injury, neocollagenesis band thickness in 21 days, and skin pigmentary safety. A 6mm punch biopsy taken at 21 days underwent Herovici staining to reveal the thickness of collagen type III neocollagenesis, confirm the presence of melanin in the epidermis, and evaluate the presence of melanophages.ResultsOn patient presentation, epidermolysis and areas of deep dermal burns were observed over the forehead and cheeks. At 14 days, multiple leucoderma scars persisted and initial perifollicular repigmentation was noticeable. At 28 days, most of the skin was repigmented; however, many areas had only perifollicular repigmentation and still very severe leucoderma. At 6 months, the skin still had small areas of leucoderma with folicular repigmentation. At 11 months the skin color was fully recovered, with minimal post-inflammatory hyperpigmentation (PIH) over the cheeks.As for the SOC animal model, at 7 days the eschar was detached, and the skin was achromic. At 21 days, skin pigmentation was completely restored without macroscopic signs of PIH. Dermatopathology evaluation revealed microscopic areas of melanophages, a fully recovered epidermal melanin, and a band of over 500 micra of collagen type III.Overall, on follicle-dense areas after chemical burn, we observed progressive full repigmentation over the course of 11 months on the patient, and by day 21 in the porcine SOC model.ConclusionsSpontaneous repigmentation occurred both after accidental deep chemical ablation to the face of a SOC patient, and on the porcine SOC model after deep chemical peel formula application.

A case of leukoderma probably caused by a soap containing neem oil

We present a rare case of leukoderma probably caused by a soap containing neem oil. Leukodermas on the face, neck, and hands matched areas where the soap was used, and spontaneous repigmentation started immediately after discontinuation of soap use. Histological evaluation revealed perivascular and perifollicular inflammatory cell infiltration with some melanophages in the superficial dermis, a decrease in melanocytes, and a lack of melanin granules.

Aberrant ETS-1 signalling impedes the expression of cell adhesion molecules and matrix metalloproteinases in non-segmental vitiligo.

Cell adhesion is a complex process that involves multiple molecules on the cell surface (ie cell adhesion molecules [CAMs]), surrounding cells and extracellular matrix (ECM). Repigmentation in vitiligo is dependent on the ECM remodelling and cellular migration, primarily attributed to the transcriptional activation of matrix metalloproteinases (MMPs). In this study, we aimed to demonstrate the role of ETS-1 signalling in the regulation of MMPs and CAMs. Therefore, we studied the expression of ETS-1, MMPs (MMP-2, MMP-9) and CAMs including E-cadherin, ITGA-1 and ICAM-1 in vitiligo (both active and stable) ex vivo. Further, we compared melanocyte morphology and their adhesion towards collagen IV and laminin between control and vitiligo groups in vitro. Also, we silenced ETS-1 in melanocytes cultured from control skin and observed post-silencing effect on above-mentioned MMPs and CAMs. We perceived absent ETS-1 and significantly reduced CAMs and MMPs in vitiligo compared with normal skin. Scanning electron microscopy (SEM) revealed a translucent material surrounding individual melanocytes in stable vitiligo and controls, whereas active vitiligo melanocytes demonstrated loss of this extracellular substance. Adhesion assays revealed significantly decreased binding of cultured melanocytes to collagen IV and laminin V plates in both stable and active vitiligo. Importantly, ETS-1 silencing resulted in significantly reduced expression of CAMs and MMPs. In conclusion, absent ETS-1 expression in both stable and active non-segmental vitiligo seems to impede the expression of CAMs, apart from MMPs, probably leading to progressive depigmentation in active disease and absence of spontaneous repigmentation in stable disease.

A cross-sectional study of spontaneous repigmentation in vitiligo.

Spontaneous regression is well documented in several chronic skin diseases such as psoriasis, alopecia areata, and atopic dermatitis. However, information on vitiligo is scarce. We studied the frequency, extent, and factors affecting spontaneous repigmentation in vitiligo. A cross-sectional descriptive study was undertaken in 167 patients with vitiligo with an emphasis on history of spontaneous repigmentation. Where available, photographs documenting spontaneous repigmentation were also obtained. Repigmentation was defined as spontaneous if it occurred when the patient was off treatment for at least 3 consecutive months. Spontaneous repigmentation occurred in 36 (21.5%) patients with complete repigmentation in 6 (3.6%) patients. The extent varied from 0.5% to 100% (mean, 35.4 ± 37.9%) of vitiliginous skin. It occurred after 3 months to 47 years (mean, 8.7 ± 9.5 years) of onset of vitiligo and persisted for 2 months to 27 years (mean, 4.4 ± 6.2 years). Diffuse repigmentation was the most common pattern observed in 20 (55.6%) patients and there was a good color match in 26 (72.2%) patients. Likelihood of spontaneous repigmentation was 3.5 times greater in patients with more than 3 years of stable disease (P = 0.001). The chief limitation was the dependence on patient recall for the data, except when documented by images. Spontaneous repigmentation occurs in one-fifth of patients with vitiligo. In some patients, the repigmentation is clinically significant and long-lasting. Considering its frequency and extent, spontaneous repigmentation should be taken into account both when evaluating novel interventions and counselling patients about the course of the disease.

Immunosuppressed cutaneous District: The finale of the fascinating farrago of confounding responses?

Immunosuppressed cutaneous District: The finale of the fascinating farrago of confounding responses?

Chemical Leukoderma.

Chemical leukoderma, often clinically mimicking idiopathic vitiligo and other congenital and acquired hypopigmentation, is an acquired form of cutaneous pigment loss caused by exposure to a variety of chemicals that act through selective melanocytotoxicity. Most of these chemicals are phenols and aromatic or aliphatic catechols derivatives. These chemicals, however, are harmful for melanocytes in individuals with an individual susceptibility. Nowadays, chemical leukoderma is fairly common, caused by common domestic products. The presence of numerous acquired confetti- or pea-sized macules is clinically characteristic of chemical leukoderma, albeit not diagnostic. Other relevant diagnostic elements are a history of repeated exposure to a known or suspected depigmenting agent at the sites of onset and a macules distribution corresponding to sites of chemical exposure. Spontaneous repigmentation has been reported when the causative agent is avoided; the repigmentation process is perifollicular and gradual, taking place for a variable period of weeks to months.

Transplantation of melanocyte stem cells in vitiliginous skin

Depigmentation in vitiligo occurs as a result of progressive loss of functioning epidermal melanocytes, and currently various modalities have been developed to re-functioning these cells. However, in area with poor melanocytes reservoir, such as old-persistent lesions or lesions on bony prominence, the modalities are hardly to achieve repigmentation. Since spontaneous repigmentation of vitiliginous skins begin mostly in follicular areas, reactivation of melanocyte precursors along the outer root sheath of hair follicle is expected to have better on this pigmentation. Melanocyte precursor came from melanocyte stem cells that originally located on bulge area of hair follicles. The latest surgical intervention in vitiligo is transplantation of melanocyte stem cells. Clinical experiments indicated that the transplantation can be performed either by transplantation of extracted follicular units or single cell suspension harvested from this area. By single cell suspension treatment, a 50 cm2 of vitiliginous skin can be handled by 15 autologous hair follicular units. These procedures are easy and can be performed by any dermatologist especially who has been trained in dermatologic surgery as well as in cellular based therapies.

Association analysis of class II cytokine and receptor genes in vitiligo patients

The loss of melanocytes in vitiligo is mainly attributed to defective autoimmune mechanisms and lately autoinflammatory mediators have become more emphasized. Among these, a number of class II cytokines and their receptors have displayed altered expression patterns in vitiligo. Thus, we selected 30 SNPs from the regions of respective genes to be genotyped in Estonian case-control sample (109 and 328 individuals, respectively). For more precise analyses, patients were divided into subgroups based on vitiligo progression activity, age of onset, sex, occurrence of vitiligo among relatives, extent of depigmented areas, appearance of Köbner’s phenomenon, existence of halo nevi, occurrence of spontaneous repigmentation, and amount of thyroid peroxidase antibodies. No associations appeared in whole vitiligo group. In subgroups, several allelic and haplotype associations were found. The strongest involved SNPs rs12301088 (near IL26 gene), that was associated with familial vitiligo and existence of halo nevi, and rs2257167 (IFNAR1 gene), that was associated with female vitiligo. Additionally, haplotypes consisting of rs12301088 and rs12321603 alleles (IL26–IL22 genes), that were associated with familial vitiligo and existence of halo nevi. In conclusion, several genetic associations with vitiligo subphenotypes were revealed and functional explanations to these remain to be determined in respective studies.

Spontaneous repigmentation in an infant with piebaldism

International Journal of DermatologyVolume 54, Issue 6 p. e244-e246 Correspondence Spontaneous repigmentation in an infant with piebaldism Laura Frances MD, Laura Frances MD frances.rodriguez.laura@gmail.com Section of Dermatology, Hospital General Universitario, Alicante, SpainSearch for more papers by this authorIsabel Betlloch MD, Isabel Betlloch MD Section of Dermatology, Hospital General Universitario, Alicante, SpainSearch for more papers by this authorMaria Leiva-Salinas MD, Maria Leiva-Salinas MD Section of Dermatology, Hospital General Universitario, Alicante, SpainSearch for more papers by this authorJuan Francisco Silvestre MD, Juan Francisco Silvestre MD Section of Dermatology, Hospital General Universitario, Alicante, SpainSearch for more papers by this author Laura Frances MD, Laura Frances MD frances.rodriguez.laura@gmail.com Section of Dermatology, Hospital General Universitario, Alicante, SpainSearch for more papers by this authorIsabel Betlloch MD, Isabel Betlloch MD Section of Dermatology, Hospital General Universitario, Alicante, SpainSearch for more papers by this authorMaria Leiva-Salinas MD, Maria Leiva-Salinas MD Section of Dermatology, Hospital General Universitario, Alicante, SpainSearch for more papers by this authorJuan Francisco Silvestre MD, Juan Francisco Silvestre MD Section of Dermatology, Hospital General Universitario, Alicante, SpainSearch for more papers by this author First published: 13 March 2015 https://doi.org/10.1111/ijd.12776Citations: 6 Conflicts of interest: None. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume54, Issue6June 2015Pages e244-e246 RelatedInformation

Leukotrichia in Stable Segmental Vitiligo: Implication of an Alternate Treatment Option

Dear Editor: Vitiligo is traditionally divided into two distinct clinical forms, nonsegmental vitiligo (NSV) and segmental vitiligo (SV). SV usually accompanies leukotrichia, which indicates that the condition is resistant to medical treatment and requires epidermal grafting1. In this case, perifollicular repigmentation was induced in a patient with SV and concurrent leukotrichia that was previously unresponsive to narrow-band ultraviolet B (NBUVB) phototherapy after the patient suffered an accidental burn on the denuded but uncovered area during phototherapy following an epidermal graft. A 12-year-old girl presented to our clinic with white patches that had initially developed on the right side of her trunk 2 years prior. Physical examination showed well-defined depigmented patches containing white hairs along the right T6~T12 dermatomes (Fig. 1). White accentuation with obvious fluorescence was detected using Wood's lamp. She had received NBUVB phototherapy for 5 months without remarkable improvement. Upon consent, a suction blister epidermal graft was performed. Due to the sizeable lesion, several sessions of epidermal grafting were required. Fig. 1 Well-defined depigmented patches along the right T6~T12 dermatomes. One week later, after we grossly concluded that the previously uncovered areas were fully recovered, phototherapy was initiated. After 3 days, the patient returned to the clinic only to display a burn on the formerly denuded but uncovered area. Further treatment was delayed until the area was completely healed, and 10 days later, treatment was re-engaged starting with 700 mJ/cm2, with an incremental 15% increase in dose during every subsequent course. Interestingly, after 2 weeks, spontaneous repigmentation at the denuded but uncovered site was observed along with that in the covered site (Fig. 2A). On the patient's subsequent visit 2 months later, the recipient area, again including the uncovered area, was almost completely pigmented (Fig. 2B). Fig. 2 (A) Diffuse and perifollicular repigmentation both on the covered and uncovered recipient site after 2 weeks. (B) Near complete repigmentation on the recipient site after 12 weeks. Surgical treatment can be considered when vitiligo does not respond to traditional treatments. The procedure is particularly suitable in cases that show complete loss of melanocytes or in cases that have a low possibility of repigmentation that is clinically indicated by the presence of leukotrichia2. It has been suggested that visualization of leukotrichia in the vitiligous lesions of patients with SV using portable digital microscopy indicates no hope of repigmentation and, therefore, that a surgical approach is recommended1. A recent preliminary study, however, reported that although tyrosinase-positive melanocytes are only observed in black hair follicles, melanocytes still exist in the white hair follicles, although they are fewer in number than those in black hair follicles2. These findings suggest that the melanocyte reservoir is not completely depleted in vitiligo lesions showing leukotrichia. According to an earlier study that revealed the promising result of combination treatment with an erbium:YAG laser and 5-fluorouracil ointment followed by NBUVB for the treatment of vitiligo, 78.1% of enrolled patients showed moderate to marked repigmentation3. In addition, microdermabrasion combined with pimecrolimus 1% cream has been reported to be effective without causing significant side effects including koebnerization in children with NSV4. The findings of these two studies suggest that epidermal damage caused by the erbium:YAG laser and microdermabrasion could induce the secretion of chemical mediators that are beneficial for melanocyte activation and enhance the NBUVB penetration and drug absorption into inactive melanocytes existing at the outer root sheath of the hair follicles. Similarly, we believe that in our case, the sunburn of the lesion uncovered by a graft after phototherapy might have induced the formation of various chemical mediators and growth factors which could stimulate epidermal melanocytes and induce the proliferation and migration of inactive melanocytes in the outer root sheaths of hair follicles in the depigmented lesions5 despite the presence of leukotrichia. The burn itself would also increase the transmittance and accessibility of NBUVB into inactive melanocytes in the outer root sheath, further inducing perifollicular repigmentation. In patients with SV, the coexistence of leukotrichia, has been considered a poor prognostic marker of disease that is often refractory to traditional treatment and eventually forces both the patient and the doctor into a surgical solution. Our case; however, shows that the few melanocytes that still remained in the hair follicles with leukotrichia could serve as a source of perifollicular repigmentation and points to an optimistic future involving treatment without the need for invasive epidermal grafting.

Spontaneous partial repigmentation of halo nevi around congenital melanocytic nevus and vitiligo in a 13-year-old boy

Spontaneous partial repigmentation of halo nevi around congenital melanocytic nevus and vitiligo in a 13-year-old boy

Premature graying of hair

Premature graying is an important cause of low self-esteem, often interfering with socio-cultural adjustment. The onset and progression of graying or canities correlate very closely with chronological aging, and occur in varying degrees in all individuals eventually, regardless of gender or race. Premature canities may occur alone as an autosomal dominant condition or in association with various autoimmune or premature aging syndromes. It needs to be differentiated from various genetic hypomelanotic hair disorders. Reduction in melanogenically active melanocytes in the hair bulb of gray anagen hair follicles with resultant pigment loss is central to the pathogenesis of graying. Defective melanosomal transfers to cortical keratinocytes and melanin incontinence due to melanocyte degeneration are also believed to contribute to this. The white color of canities is an optical effect; the reflection of incident light masks the intrinsic pale yellow color of hair keratin. Full range of color from normal to white can be seen both along individual hair and from hair to hair, and admixture of pigmented and white hair is believed to give the appearance of gray. Graying of hair is usually progressive and permanent, but there are occasional reports of spontaneous repigmentation of gray hair. Studies evaluating the association of canities with osteopenia and cardiovascular disease have revealed mixed results. Despite the extensive molecular research being carried out to understand the pathogenesis of canities, there is paucity of effective evidence-based treatment options. Reports of repigmentation of previously white hair following certain inflammatory processes and use of drugs have suggested the possibility of cytokine-induced recruitment of outer sheath melanocytes to the hair bulb and rekindled the hope for finding an effective drug for treatment of premature canities. In the end, camouflage techniques using hair colorants are outlined.

Vitiligo régressif au début d’un traitement antirétroviral : syndrome de reconstitution immunitaire ?

Immune reconstitution inflammatory syndrome (IRIS) includes all signs occurring during the reconstitution of an extensive and insufficiently regulated immune response to an infective or a non-infective antigen and observed during the immune suppression phase in an individual. We report a case of vitiligo appearing after the initiation of antiretroviral treatment and with repigmentation during the course of the treatment. A 30-year-old man, seropositive for HIV1-M, consulted for a diffuse eruption of hypopigmented and achromic macules. The lesions appeared 7 weeks after the start of antiretroviral therapy with zidovudine, lamivudine and efavirenz, starting on the forearm and spreading to the remainder of the skin. At control visits during the ensuing two months, gradual repigmentation of the achromic macules was noted. Plasma viral load, determined only during the treatment period, was less than 40 copies/ml (1.60(log)). This report concerns an original case of vitiligo occurring at the start of antiretroviral treatment in an HIV-positive patient, with spontaneous repigmentation during treatment. The chronology points to a hypothesis of immune reconstitution inflammatory syndrome (IRIS), despite the absence of any indication of the patient's viral load prior to therapy.

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

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

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

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.

Vitiligo: A review of the published work

Vitiligo is a common depigmenting skin disorder, characterized by acquired, idiopathic, progressive, circumscribed hypomelanosis of the skin and hair, with total absence of melanocytes microscopically. It occurs worldwide, with an incidence rate of between 0.1% and 2%. Vitiligo is an important skin disease having a major impact on the quality of life of the patient suffering from it. The causes of this condition are uncertain but seem to be dependent on the interaction of genetic, immunological and neurological factors. Vitiligo coexists with other autoimmune disorders, Sutton or halo nevus, and malignant melanoma. The substantial disfigurement associated with vitiligo can cause serious emotional stress for the patient, which necessitates treatment. Because its pathogenesis is still not understood, there is a plethora of different treatments. Among them, topical steroids and narrowband ultraviolet B monotherapy were the most common as current treatments for localized and generalized vitiligo, respectively. Cosmetic improvement can be achieved by camouflage products and self-tanning dyes. The course of vitiligo is unpredictable, but often progressive. Spontaneous repigmentation may occur in a few people (10–20%), mainly in children, but this tends to be only partial and on sun-exposed areas. In this article, we review vitiligo as a whole, including epidemiology, pathogenesis and etiology, histopathology, clinical manifestations, classification, clinical variants, diagnosis and differential diagnoses, specific investigation, treatment, prognosis, psychosocial view and its association with other disorders.

Response of vitiligo to once‐ vs. twice‐daily topical tacrolimus: a controlled prospective, randomized, observer‐blinded trial

A few studies on the treatment of vitiligo with topical tacrolimus have been published and showed promising results. However, most of these trials were uncontrolled. This study aims to assess the response of vitiligo to once- or twice-daily treatment with 0.1% tacrolimus in a controlled, randomized, observer-blinded study. Seventeen patients with generalized vitiligo were enrolled in this study. In each patient, two lesions were selected and randomized to treatment with either once- or twice-daily application of 0.1% tacrolimus for a total period of 6 months. In 10 patients, a third patch was left untreated to serve as a control. Fifteen patients with 40 target lesions completed the study. Twice-daily treatment induced excellent (> 75%) repigmentation in two lesions, moderate (> 25-50%) and poor (1-25%) repigmentation in four lesions each, and no response in five lesions. Once-daily treatment resulted in moderate repigmentation in two lesions and poor repigmentation in five lesions, whereas no effect was observed in the remaining eight lesions. One out of 10 control lesions developed moderate spontaneous repigmentation, the other nine remained unchanged. Besides the frequency of tacrolimus application, the treatment outcome was determined by the localization of the affected areas with the facial region showing the best response. Tacrolimus ointment appears to be an effective treatment option for facial vitiligo. A guarded prognosis is advisable for vitiliginous lesions on other localizations. Treatment must be applied twice daily for optimum response.

Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo-controlled double-blind study

Background 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. Objectives 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. Methods 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. Results 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−2and 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). Conclusions 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.

Topical calcipotriol as monotherapy and in combination with psoralen plus ultraviolet A in the treatment of vitiligo

Background 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. Objectives 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. Methods Twenty-six patients with vitiligo affecting 5–40% of their skin were recruited. Twenty-two were treated with twice-daily topical calcipotriol monotherapy (50 µg g−1) and four were placed on combination treatment with twice-daily topical calcipotriol 50 µg g−1 in conjunction with topical or oral 8-methoxypsoralen PUVA three times weekly. Results 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. Conclusions 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.