Cysteamine Isobionic-Amide Complex Versus Kligman's Formula for the Treatment of Melasma: Equal Efficacy and Rapid Onset of Action.

BACKGROUND: Modified Kligman's formula (mKF) is the gold standard treatment for melasma; however, its prolonged use is not recommended due to side effects. Cysteamine is a potent, safe, and effective depigmenting agent. Here, we conducted a double-blind, randomized, and placebo-controlled clinical trial to assess the efficacy of cysteamine isobionic-amide -- a complex with enhanced depigmenting efficacy -- and compared it to mKF for the treatment of melasma. METHODS: This study involved a total of 80 patients divided into 3 groups: cysteamine-isobionic amide, placebo, or mKF. The modified Melasma Area Severity Index (mMASI) score and spectrophotometric evaluation were conducted at baseline, week 4, week 8, and week 16. Dermatological assessment, patients’ feedback, and satisfaction including quality-of-life scores were also collected. RESULTS: At week 4, cysteamine isobionic-amide and mKF groups showed an equivalent onset of action in terms of mMASI and skin pigmentation contrast reduction. The 2 groups significantly reduced melasma severity and improved the overall skin condition with a comparable efficacy at week 16. Quality of life of melasma patients was significantly improved in the cysteamine isobionic-amide group at week 8 and further at week 16 (P<0.001) compared to the mKF group. Patients’ feedback and satisfaction were higher with the cysteamine isobionic-amide product compared to mKF. CONCLUSION: Cysteamine isobionic-amide provided a rapid onset of action and was as effective as the mKF for the treatment of melasma. The data suggest that cysteamine isobionic-amide could potentially be an acceptable alternative to mKF for the long-term treatment of melasma. J Drugs Dermatol. 2024;23(2):9-16.  doi:10.36849/JDD.7428.

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.

Topical Stabilized Cysteamine as a New Treatment for Hyperpigmentation Disorders: Melasma, Post-Inflammatory Hyperpigmentation, and Lentigines.

Cysteamine is an aminothiol naturally present in cells of the human body as an antioxidant resulting from the degradation of Coenzyme A. Physiologically it is well distributed in mammalian tissues. Highly concentrated in human milk, cysteamine acts as an intrinsic antioxidant and is known for its protective role. Multiple studies now document that cysteamine is a potent skin depigmenting agent. Historically, its rapid oxidation and very offensive odor made it difficult for topical use until recently when stabilization of cysteamine was achieved. This has led to an acceptable galenical form for topical application. Since 2015, the efficacy, safety, and tolerability of stabilized cysteamine (st.Cys) has been demonstrated in multiple clinical studies, as well a case reports. Stabilized cysteamine has demonstrated significant effectiveness for the treatment of melasma by two double-blind randomized and vehicle control trials. Stabilized cysteamine (st.Cys) has shown to be as effective as well-known depigmenting therapies, including triple combination cream or tranexamic acid mesotherapy, with higher tolerability. A recent clinical trial has shown considerable efficacy of topical cysteamine for the treatment of senile lentigines, which are usually considered to be resistant to topical depigmenting agents. Topical stabilized cysteamine can be regarded to as one of the most potent treatments available for hyperpigmentation disorders in humans. J Drugs Dermatol. 2021;20(12): 1276-1279. doi:10.36849/JDD.6367.

The Pathogenesis and Management of Acne-Induced Post-inflammatory Hyperpigmentation.

Acne vulgaris is a common inflammatory disease. Among patients with darker skin phototypes (Fitzpatrick III-VI), the inflammatory processes of acne stimulate excess melanogenesis and abnormal melanin deposition, leading to pigmentary sequelae known as post-inflammatory hyperpigmentation and post-inflammatory erythema in all skin tones, although post-inflammatory hyperpigmentation is more common in darker skin and post-inflammatory erythema in lighter skin. These pigmentary alterations can be long lasting and are often more distressing to patients than the active acne lesions. This article discusses what is known about acne-related pigmentation, much of which is extrapolated from general study of nonspecific pigment deposition. Because dyspigmentation poses both a significant clinical concern to patients and a therapeutic challenge to clinicians, we formed a working group consisting of pigmentary experts with the aim of increasing awareness and education of acne-related pigmentary sequelae.

Comparison of 311-nm Titanium:Sapphire laser and 308-nm excimer laser treatment for vitiligo: A randomized controlled non-inferiority trial.

OBJECTIVES: The 308-nm excimer laser (EL) has been widely used for localized vitiligo. The recently developed Titanium:Sapphire laser, emits a wavelength of 311 nm, would be expected to be as effective as excimer laser in treatment of vitiligo but few controlled trials have been reported. We sought to compare the efficacy and safety of the TSL and EL as vitiligo treatments. METHODS: A randomized controlled non-inferiority trial based on split-body was conducted. Patients with stable vitiligo between June 2016 and May 2017 were enrolled. Paired symmetrical vitiligo lesions were randomized to either the EL or TSL treatment group, and treated with a 308-nm EL or a 311-nm TSL twice weekly for 12 weeks. The extent of repigmentation was assessed every 4 weeks, and the non-inferiority margin was set to 10%. We also recorded any adverse events. RESULTS: Seventy-four paired lesions in 21 patients were assigned to both the EL group or TSL group. The mean difference between two groups (EL minus TSL) was -2.862%, and the 95% confidence interval (-6.531% to 0.807%) was lower than the non-inferiority margin. No serious adverse events were noted in either group. CONCLUSIONS: The Titanium:Sapphire laser showed similar therapeutic effect to excimer laser in localized vitiligo with good safety profiles in this non-inferiority randomized controlled trial. The Titanium: Sapphire laser can serve as an alternative treatment option for localized vitiligo. Lasers Surg. Med. 51:239-244, 2019. © 2019 Wiley Periodicals, Inc.

Depigmentation Therapies for Vitiligo.

The general goals of medical management of vitiligo are to repigment vitiliginous areas of skin and to stabilize the progression of depigmentation. However, for some patients with vitiligo affecting extensive body surface areas who are unresponsive to repigmentation therapies, depigmentation of the remaining normal skin may be a better choice. Candidates for depigmentation therapy should be carefully screened and patient education is essential. Permanent topical therapies used for depigmentation include monobenzyl ether of hydroquinone, 4-methoxyphenol, and 88% phenol. Physical modalities, such as cryotherapy and lasers, are also being used successfully.

The Role of Diet and Supplements in Vitiligo Management.

Vitiligo is an autoimmune disorder that involves the interplay between oxidative stress and the immune system. Preliminary observations suggest that the presence of gluten in the diet may play a role in vitiligo development in some patients, but to date vitiligo-specific diets have not been studied. The role of oral supplements, including vitamins, minerals, and botanicals, is increasingly being investigated as adjuncts to conventional medical treatment due to their antioxidant and immunomodulatory activity. Studies suggest that many of these agents may have some efficacy as monotherapy, but more often as adjuncts to topical agents and phototherapy.

Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial.

IMPORTANCE: Narrowband UV-B (NB-UV-B) phototherapy is used extensively to treat vitiligo. Afamelanotide, an analogue of α-melanocyte-stimulating hormone, is known to induce tanning of the skin. OBJECTIVE: To evaluate the efficacy and safety of combination therapy for generalized vitiligo consisting of afamelanotide implant and NB-UV-B phototherapy. DESIGN, SETTING, AND PARTICIPANTS: This study was performed in 2 academic outpatient dermatology centers and 1 private dermatology practice. We enrolled men and women 18 years or older with Fitzpatrick skin phototypes (SPTs) III to VI and a confirmed diagnosis of nonsegmental vitiligo that involved 15% to 50% of total body surface area. Vitiligo was stable or slowly progressive for 3 months. Patients were randomized to combination therapy (n = 28) vs NB-UV-B monotherapy (n = 27). After 1 month of NB-UV-B phototherapy, 16 mg of afamelanotide was administered subcutaneously to the combination therapy group monthly for 4 months while NB-UV-B phototherapy continued; the other group continued to receive NB-UV-B monotherapy. INTERVENTIONS: Narrowband UV-B monotherapy vs combined NB-UV-B phototherapy and afamelanotide. MAIN OUTCOMES AND MEASURES: Response on the Vitiligo Area Scoring Index and Vitiligo European Task Force scoring system. RESULTS: Response in the combination therapy group was superior to that in the NB-UV-B monotherapy group (P < .05) at day 56. For the face and upper extremities, a significantly higher percentage of patients in the combination therapy group achieved repigmentation, and at earlier times (face, 41.0 vs 61.0 days [P = .001]; upper extremities, 46.0 vs 69.0 days [P = .003]). In the combination therapy group, repigmentation was 48.64% (95% CI, 39.49%-57.80%) at day 168 vs 33.26% (95% CI, 24.18%-42.33%) in the NB-UV-B monotherapy group. Notable adverse events included erythema in both groups and minor infections and nausea in the combination therapy group. Comparison between Fitzpatrick SPTs showed patients with SPTs IV to VI in the combination therapy group had improvement in the Vitiligo Area Scoring Index at days 56 and 84 (P < .05); no significant difference was noted in patients with SPT III. CONCLUSIONS AND RELEVANCE: A combination of afamelanotide implant and NB-UV-B phototherapy resulted in clinically apparent, statistically significant superior and faster repigmentation compared with NB-UV-B monotherapy. The response was more noticeable in patients with SPTs IV to VI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01430195.

The efficacy of afamelanotide and narrowband UV-B phototherapy for repigmentation of vitiligo.

BACKGROUND: Vitiligo is characterized by depigmented patches of skin due to loss of cutaneous melanocytes. Many recent studies have demonstrated defects in the melanocortin system in patients with vitiligo, including decreased circulating and lesional skin levels of α-melanocyte-stimulating hormone (α-MSH). Afamelanotide is a potent and longer-lasting synthetic analogue of naturally occurring α-MSH. OBSERVATIONS: We describe the preliminary results of 4 patients with generalized vitiligo who developed repigmentation using afamelanotide in combination with narrowband UV-B (NB-UV-B) phototherapy. Patients were treated 3 times weekly with NB-UV-B and starting in the second month received a series of 4 monthly implants containing 16 mg of afamelanotide. Afamelanotide induced faster and deeper repigmentation in each case. All patients experienced follicular and confluent areas of repigmentation within 2 days to 4 weeks after the initial implant, which progressed significantly throughout treatment. All patients experienced diffuse hyperpigmentation. CONCLUSIONS: We propose that afamelanotide represents a novel and potentially effective treatment for vitiligo. The combined therapy of NB-UV-B and afamelanotide appears to promote melanoblast differentiation, proliferation, and eumelanogenesis. Further studies are necessary to confirm these observations.

A histological examination for skin atrophy after 6 months of treatment with fluocinolone acetonide 0.01%, hydroquinone 4%, and tretinoin 0.05% cream.

Melasma is a common disorder affecting a significant percentage of the population, particularly those with skin of color. Therapy with hydroquinone, a depigmenting agent, as a single agent or in combination with other agents has been used with variable success. A triple-combination (TC) cream combining hydroquinone 4% with tretinoin 0.05% and fluocinolone acetonide 0.01% was developed for the treatment of melasma. We studied the use of TC cream for 24 weeks and had tissue samples for all time points in 62 patients with moderate to severe melasma. The atrophogenic potential of TC cream was evaluated through serial histopathologic examination of skin biopsies. No statistically significant histopathologic signs of atrophy of the epidermis or dermis were noted at any time point throughout the study. There was a marked reduction in epidermal melanin in treated subjects; however, we did not observe any significant difference in baseline and treated samples in the amount of perivascular inflammatory infiltrate, dermal mucin, keratinocyte and melanocyte atypia, or mast cells, consistent with findings of previous studies where topical retinoids were used. An increase in the mean number of blood vessels per square millimeter of tissue was observed in 2 study cohorts between baseline and week 24. These results suggest that the risk of skin atrophy with 24-week use of TC cream for the treatment of melasma is very low.

Microdermabrasion.

BACKGROUND: Microdermabrasion has become one of the most popular forms of superficial resurfacing. The benefits and efficacy of microdermabrasion remain an intensely debated topic among dermatologic surgeons. OBJECTIVE: This article reviews the efficacy, safety, epidermal barrier function, histopathologic effects, complications, advantages, and disadvantages of microdermabrasion. CONCLUSION: In general, microdermabrasion studies have been conducted in small groups of patients. Protocols, units, and settings have differed. There remains a major disparity between the popularity of microdermabrasion in the public sector and cohesive and comprehensive scientific data documenting the efficacy of the procedure.

Skin barrier changes induced by aluminum oxide and sodium chloride microdermabrasion.

BACKGROUND: Microdermabrasion has become an extremely popular method for superficial resurfacing. Despite the popularity of this technique, published studies of skin barrier function changes following microdermabrasion are lacking. OBJECTIVE: To study assessed transepidermal water loss (TEWL), hydration, pH, and sebum production following aluminum oxide (Al2O3) and sodium chloride (NaCl) microdermabrasion. METHODS: Eight patients were included in this split face study. Transepidermal water loss, stratum corneum hydration, skin pH, and sebum production measurements were taken from the right and left sides of the face at baseline. One side of the face was treated with Al2O3 microdermabrasion and the other side with NaCl microdermabrasion. Measurements were repeated at 24 hours and 7 days. RESULTS: Both NaCl and Al2O3 microdermabrasion was associated with a statistically significant increase in TEWL at 24 hours. In contrast, at 7 days, levels of TEWL were decreased to less than baseline. In addition, an increase in hydration was observed 24 hours after NaCl and Al2O3 microdermabrasion. Hydration in NaCl-treated areas remained significantly increased at 7 days. CONCLUSION: The results of this investigation suggest that both NaCl and Al2O3 microdermabrasion alter the epidermal barrier. These changes in epidermal barrier function may be responsible for the clinical improvement following microdermabrasion.