Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Efficacy and safety of a novel triple combination cream compared to Kligman's trio for melasma: A 24-week double-blind prospective randomized controlled trial.

BACKGROUND: Kligman's trio (KT), combining hydroquinone, retinoic acid and corticosteroid, is considered as the gold standard treatment of melasma. Its efficacy has never been matched before, but it is tempered by frequent adverse effects. OBJECTIVE: To assess the efficacy and tolerance of a New Trio (NT) combination with isobutylamido-thiazolyl-resorcinol, retinoic acid and cortosteroid compared to KT. METHODS: We conducted a 24-week monocentric trial, randomized, double-blind, controlled versus KT, with 40 melasma patients. NT and KT were applied for 12 weeks and associated with the same sunscreen applied for 24 weeks. The primary endpoint was the modified Melasma Area Severity Index (mMASI) at 12 weeks. Patient quality of life was investigated using MelasQoL. RESULTS: After 12 weeks, KT and NT groups both demonstrated a significant improvement in mMASI, respectively -2.84 (SE 0.69, p < 0.0002) and -4.33 (SE 0.71, p < 0.0001). The mean difference between the two groups was -1.49 (IC 95% -3.52 to 0.54, p = 0.14). MelasQoL improvement was -6.66 (SE 3.29, p = 0.0515) with KT and -12.57 (SE 3.29, p = 0.0006) with NT. CONCLUSION: The NT combination appears to be an effective treatment option for treating melasma and could be considered as a well-tolerated alternative to KT.

Expert opinion about laser and intense pulsed light (IPL)-induced leukoderma or vitiligo: a cross-sectional survey study.

Vitiligo patients may desire laser hair removal, skin rejuvenation, vascular treatments, and other laser or intense pulsed light (IPL) assisted treatments. However, there is a risk of inducing new depigmented patches (Koebner phenomenon). In absence of guidelines on the safe use of laser or IPL in vitiligo patients, dermatologists tend to be reluctant to administer these treatments. The aim of this survey study was to provide an estimation of the occurrence and related risk factors of laser/IPL-induced leukoderma or vitiligo. A cross-sectional survey study was performed among 15 vitiligo experts from 11 countries, with 14 questions about affected patients, involved laser/IPL treatments and the physicians' approach. In a total of 11,300 vitiligo patients, laser/IPL-induced leukoderma or vitiligo was reported in 30 patients (0.27%). Of these, 12 (40%) patients had a medical history of vitiligo and seven (58%) of these patients had stable (> 12 months) vitiligo before the treatment. Most frequently reported were hair removal procedures and localization of the face and legs. Side effects like blistering, crusting, and erosions occurred in 56.7% of the cases. These vitiligo experts based their advice on the risk of the laser treatment on stability of the vitiligo (43%) and activity signs (50%), and 50% discuss the risks before starting a laser treatment. Relevant activity signs are the Koebner phenomenon (57.1%), confetti-like lesions (57.1%) and hypochromic borders (50%). Laser-induced leukoderma or vitiligo is an uncommon phenomenon. Remarkably, a minority had a medical history of vitiligo of which 58% were stable. Consequently, most cases could not have been prevented by not treating vitiligo patients. However, a majority had laser/IPL-induced skin damage. Therefore, caution is advised with aggressive settings and test-spots prior to the treatment are recommended. This study showed significant variation in the current recommendations and approach of vitiligo experts regarding laser/IPL-induced leukoderma or vitiligo.

[Vitiligo, no longer a fatality in 2023].

Vitiligo is an acquired auto-inflammatory disorder characterized by a depigmentation. It is a polygenic disease developed in a context of allelic variations. Its pathophysiology is complex, associating intrinsic skin defects, exposome triggering factors and innate then adaptive auto-immune activation leading to the loss of melanocytes. The diagnosis is clinical. Nevertheless, Wood's lamp is mandatory to assess the lesions and their activity, especially in fair-skinned patients. The management of vitiligo is long and aims to halt the depigmentation process and to repigment the affected areas. This requires a combination of immunosuppressive topical or systemic treatment with ultraviolet rays from phototherapy or sun exposure.

Le vitiligo est une dépigmentation acquise bien limitée, d'origine auto-immune. Il s'agit d'une maladie polygénique survenant dans un contexte de variations alléliques prédisposant son apparition. Sa physiopathologie est complexe et associe des défauts intrinsèques de la peau, des facteurs déclenchants liés à l'exposome et une activation immunitaire innée, puis adaptative, conduisant à la perte des mélanocytes. Son diagnostic est clinique mais la lumière de Wood est indispensable pour apprécier les lésions et leur activité, notamment sur peau claire. La prise en charge du vitiligo est longue et a pour but d'interrompre la dépigmentation et de repigmenter les zones lésionnelles. Pour cela, il faut associer un traitement immunosuppresseur topique ou systémique à des rayons ultraviolets, soit naturels, soit de la photothérapie.

The Damaging Effects of Long UVA (UVA1) Rays: A Major Challenge to Preserve Skin Health and Integrity.

Within solar ultraviolet (UV) light, the longest UVA1 wavelengths, with significant and relatively constant levels all year round and large penetration properties, produce effects in all cutaneous layers. Their effects, mediated by numerous endogenous chromophores, primarily involve the generation of reactive oxygen species (ROS). The resulting oxidative stress is the major mode of action of UVA1, responsible for lipid peroxidation, protein carbonylation, DNA lesions and subsequent intracellular signaling cascades. These molecular changes lead to mutations, apoptosis, dermis remodeling, inflammatory reactions and abnormal immune responses. The altered biological functions contribute to clinical consequences such as hyperpigmentation, inflammation, photoimmunosuppression, sun allergies, photoaging and photocancers. Such harmful impacts have also been reported after the use of UVA1 phototherapy or tanning beds. Furthermore, other external aggressors, such as pollutants and visible light (Vis), were shown to induce independent, cumulative and synergistic effects with UVA1 rays. In this review, we synthetize the biological and clinical effects of UVA1 and the complementary effects of UVA1 with pollutants or Vis. The identified deleterious biological impact of UVA1 contributing to clinical consequences, combined with the predominance of UVA1 rays in solar UV radiation, constitute a solid rational for the need for a broad photoprotection, including UVA1 up to 400 nm.

Apremilast in Combination with Narrowband UVB in the Treatment of Vitiligo: A 52-Week Monocentric Prospective Randomized Placebo-Controlled Study.

BACKGROUND: Scientific rationale and encouraging first clinical results suggest the interest of using apremilast for treating vitiligo. OBJECTIVE: This study aimed to compare the efficacy of apremilast in combination therapy with narrowband (NB)-UVB versus placebo and NB-UVB treatment for repigmentation in patients with nonsegmental vitiligo. DESIGN: This was a 52-week prospective randomized placebo-controlled study. PARTICIPANTS: Adult patients with vitiligo participated. INTERVENTIONS: Group A received, in addition to phototherapy, apremilast at the label dosage, and group B received placebo. After 24 weeks, patients who responded (decreased Vitiligo Area Scoring Index >30%) were rerandomized to receive apremilast or placebo, combined with twice-weekly NB-UVB for 24 additional weeks. Main outcome and measure: The primary outcome measure was the comparison between the two groups of the Vitiligo Area Scoring Index score at 24 weeks. RESULTS: Eighty patients were randomized (40 in each group). After 24 weeks, the mean Vitiligo Area Scoring Index score decreased from 23.63 to 19.49 (P = 0.011) in the apremilast + UVB group and from 21.57 to 15.25 (P < 0.0001) in the placebo + UVB group. The difference between the two groups was not statistically significant (P = 0.18). No statistically significant differences were observed between the two groups after an additional 24 weeks of treatment. CONCLUSIONS AND RELEVANCE: Apremilast does not bring any benefit to NB-UVB for treating vitiligo.

Medical and Maintenance Treatments for Vitiligo.

Medical treatments alone, or in combination with phototherapy, are key approaches for treating nonsegmental vitiligo and, to a lesser extent, segmental vitiligo. The treatments are useful for halting disease progression and have been proven effective for inducing repigmentation and decreasing risk of relapses. Although the treatments have side effects and limitations, vitiligo often induces a marked decrease in quality of life and in most cases the risk:benefit ratio is in favor of an active approach. Systemic and topical agents targeting the pathways involved in loss of melanocytes and in differentiation of melanocyte stem cells should provide more effective approaches in the near future.

The skin aging exposome.

The term "exposome" describes the totality of exposures to which an individual is subjected from conception to death. It includes both external and internal factors as well as the human body's response to these factors. Current exposome research aims to understand the effects all factors have on specific organs, yet today, the exposome of human skin has not received major attention and a corresponding definition is lacking. This review was compiled with the collaboration of European scientists, specialized in either environmental medicine or skin biology. A comprehensive review of the existing literature was performed using PubMed. The search was restricted to exposome factors and skin aging. Key review papers and all relevant, epidemiological, in vitro, ex vivo and clinical studies were analyzed to determine the key elements of the exposome influencing skin aging. Here we propose a definition of the skin aging exposome. It is based on a summary of the existing scientific evidence for the role of exposome factors in skin aging. We also identify future research needs which concern knowledge about the interaction of distinct exposomal factors with each other and the resulting net effects on skin aging and suggest some protective measures.

Signalling and chemosensitivity assays in melanoma: is mutated status a prerequisite for targeted therapy?

Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MAPK pathway was activated and a significant response to sorafenib, a mitogen-activated protein kinase (MAPK)/RAF inhibitor, was found in signalling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months, with marked necrosis in some lesions. Chemosensitivity assays and signalling pathway studies could be of great value in addition to genotyping for assessing the most appropriate treatment in melanoma.

What's new in hypochromy.

Hypochromy is a common dermatological disorder. However, its treatment still gives unsatisfactory results. Interesting clues into the understanding of the pathophysiology of hypochromy have been recently brought about thanks to the pigmentary side effects reported with the new tyrosine kinase inhibition treatments. New therapeutic approaches to hypochromy are further discussed.

Use of the 308-nm excimer laser for psoriasis and vitiligo.

The 308-nm excimer laser represents the latest advance in the concept of selective phototherapy. It emits a wavelength in the UV-B spectrum and thus shares the same indications as conventional phototherapy. Like other laser devices, the 308-nm excimer laser emits a monochromatic and coherent beam of light, can selectively treat a lesion while sparing surrounding healthy skin, and can deliver high fluencies. Clinicians have taken advantage of these properties to treat dermatologic disorders since 1997, with psoriasis and vitiligo attracting most attention. Initially, high fluencies (minimal erythemal dose, 8-16) were used, with excellent clinical results, to treat psoriasis vulgaris. The significance of side effects and the potential long-term carcinogenic risk associated with such fluencies have resulted in medium doses (about 3 minimal erythemal dose) being recommended, however. Interestingly, taking advantage of the selectivity of the laser, newer treatment protocols adapt the dose to the lesion and not to the minimal erythemal dose, as is the case for conventional phototherapies. Many prospective study series have also shown the efficacy and the good tolerance of the 308-nm excimer laser in the treatment of localized vitiligo. Induced rates of repigmentation seem to be higher than with narrowband UV-B. Moreover, the selectivity of the treatment prevents irradiation of healthy skin and limits unsightly tanning of surrounding skin. Aesthetically pleasing results are usually not achieved in extremities and bony prominences, which are not good indications for this technique. Combining the 308-nm excimer laser with 0.1% tacrolimus ointment has provided very interesting results, which need to be confirmed in larger series. The absence of actual data concerning the long-term risk for skin cancer after this treatment means that it should be considered with caution. Combination with topical steroids appears to be synergistic and potentially reduces long-term side effects; again, prospective data are lacking.

Melanin pigmentary disorders: treatment update.

Most of the melanin pigmentary disorders are cosmetically important and have a strong impact on the quality of life of affected individuals. This article examines recent advances in the treatment of melanin pigmentary disorder including hypermelanosis and hypomelanosis. The development of laser technologies has completed the use of the increasing number of bleaching agents in treating hyperpigmented lesions. The treatment of hypomelanotic disorders is still often disappointing, but new therapeutic options provide encouraging results.

[The 308 nm excimer laser in dermatology]. / Le laser excimer à 308 nm en dermatologie.

THE EFFICACY OF THE 308 NM EXCIMER LASER in the treatment of common psoriasis has been demonstrated. THE DOSES USED have progressively decreased, hence, limiting the adverse events that appear redhibitory with high doses. THE ADAPTATION OF THE DOSES not to the patients themselves but to each of the plaques treated should reduce the number of sessions and the cumulated close necessary to obtain clinical remission. THE 308 NM EXCIMER LASER is effective and tolerance is good in the treatment of vitiligo. It should be proposed for limited vitiligo and essentially of the "UV sensitive" areas, which have shown aesthetically correct percentage of repigmentation. THE PLACE AND INTEREST of its association with other treatments, notably with topical tacrolimus, remains to be defined. Although the results obtained in the treatment of vitiligo are promising, they have to be confirmed in larger cohorts and ensure the absence of median and long term side effects. This therefore limits its use in combined treatments in the context of controlled clinical traits. THE 30 NM EXCIMER LASER IS AN EFFECTIVE AND WELL TOLERATED TREATMENT in localised and non-nodular forms of mycosis fungoid (MF). Although the number of patients treated is limited, the clinical and histological cure observed demonstrates the interest of this new technique in the treatment of MF. These results must be confirmed in a greater number of patients. THE 308 NM EXCIMER LASER is an interesting therapeutic alternative in the treatment of plaques of alopecia areata, erosive oral lichen planus, post-surgical hypopigmentation, vergetures and localised forms of atopic dermatitis. Because of the sparcity of data and in the absence of long term follow-up, it must not be proposed in first intention.