Hyperpigmented Macules and Patches on the Face: Exogenous Ochronosis or Lichen Planus Pigmentosus?

We present a case of a patient with a 10-year history of blue-black macules and patches on the face and an associated history of skin-lightening cream usage. The skin lightening cream contained hydroquinone, which is often associated with exogenous ochronosis (EO). Interestingly, the biopsy did not show characteristic findings of ochronosis, confusing the final diagnosis, however discontinuing the skin-lightening creams halted the progression of the patient's skin lesions supporting a diagnosis of EO. EO presents as asymptomatic hyperpigmentation after using products containing hydroquinone. This condition is most common in Black populations, likely due to the increased use of skin care products and bleaching cream containing hydroquinone in these populations. Topical hydroquinone is FDA-approved to treat melasma, chloasma, freckles, senile lentigines, and hyperpigmentation and is available by prescription only in the US and Canada. However, with the increased use of skin-lightening creams in certain populations, it is important for dermatologists to accurately recognize the clinical features of exogenous ochronosis to differentiate it from similar dermatoses. An earlier diagnosis can prevent the progression to severe presentations with papules and nodules. We summarize the clinical presentations diagnostic features, and treatment pearls, concluding with a discussion of the differential diagnoses.  J Drugs Dermatol. 2024;23(7):567-568.     doi:10.36849/JDD.8248.

An update on the safety of hydroquinone.

Hydroquinone has been used for years for multiple conditions, including melasma, post-inflammatory hyperpigmentation, dyschromia from photoaging, and solar lentigines. It is known to be a very effective lightening agent, but several concerns have been raised about this widely used agent. The recent U.S. ban on over-the-counter skin lightening products containing hydroquinone has prompted further questioning of the safety of this widely used agent. While there have been prior informative, large-scale reviews on the safety of hydroquinone, new findings have since been reported. Here, we provide an updated review of studies published in the past 15 years on hydroquinone safety.

Efficacy and tolerability of a depigmenting gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that targets the biological processes regulating skin melanogenesis.

BACKGROUND: The diverse causes of hyperpigmentation and complex nature of melanogenesis make it a challenge to manage. Current approaches either fail to deliver effective pigmentation control or have undesirable safety profiles that preclude their long-term use. AIMS: To evaluate the capacity of a cosmetic gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that was designed to target the biological processes regulating skin melanogenesis to attenuate melanin production in vitro and reduce hyperpigmentation clinically. METHODS: Capacity to reduce melanin production in vitro was determined in melanocyte-containing reconstructed human epidermis (RHEm). Clinical efficacy and skin tolerability following twice daily application were assessed in 35 subjects with slight to moderate facial hyperpigmentation by instrumental (VISIA®-CR, Mexameter®) and clinical (mMASI, clinical score, IGA for hyperpigmentation) evaluation on D14, D28, D56, and D84. Maintenance of pigmentation control was followed up 1 month after cessation of treatment on D112. RESULTS: In RHEm in vitro, melanin production was reduced by 50.0% from baseline (D0) on D14 (p < 0.001) and by 67.0% on D21 (p < 0.001). Clinical reductions from baseline in brown spots count (-9.0%; p < 0.05), brown spots area (-16.7%; p < 0.001), and the melanin index (-11.4%; p < 0.001) were observed within 14 days of use. Statistically significant improvements in all clinical parameters were achieved by D28. By the end of treatment on D84, the number and surface area of brown spots were reduced by 28.4% and 40.3% compared to D0, respectively (p < 0.001, both), the melanin index was reduced by 31.1% (p < 0.001), mMASI was reduced by 63.0% (p < 0.001), and skin luminosity was increased by 79.0% (p < 0.001). IGA was reduced from 2.3 on D0 to 1.3 on D84 (p < 0.001). Improvements to all these parameters were maintained until D112, 1 month after termination of treatment. The product also demonstrated very good skin tolerability. CONCLUSION: A gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, and hydroxy acids, designed to target the biological processes regulating skin melanogenesis, demonstrates rapid, robust, and sustained pigmentation control in this cohort.

Skin lightening properties of zerumbone cream: A placebo-controlled study.

OBJECTIVE: Despite the demonstrated anti-melanogenic and UV protective effects of Zerumbone (ZER) in vitro, there is a lack of clinical trials that have been done to assess these properties. The primary objective of this study was to assess the effectiveness of ZER in lightening the skin tone of human participants with a single-blind approach. METHODS: Twenty-six participants were randomly assigned to two groups to investigate the application location (left or right volar forearm) for the placebo and ZER creams. Both creams were topically administered to the volar forearms twice daily over a duration of 4 weeks. Initial skin irritation was assessed before and 30 min after applying creams. The melanin and erythema levels were quantified with Mexameter MX 18. RESULTS: Twenty participants were included in the analysis. The cream formulation had excellent physical properties and was well-received by the participants. The initial skin irritation study results indicated that neither of the creams elicited an allergic reaction. The administration of ZER cream resulted in a statistically significant reduction in melanin levels (p < 0.05) after 1 week compared to the initial baseline. Furthermore, after 2 weeks of application, ZER cream demonstrated significant differences in melanin levels compared to placebo (p < 0.05). No adverse effects were observed in the group using ZER cream. CONCLUSION: ZER demonstrated significant potential as a skin-lightening agent.

Efficacy and safety of novel topical pigment-correcting regimen with biweekly diamond tip microdermabrasion procedures on facial hyperpigmentation.

BACKGROUND: Facial hyperpigmentation can negatively affect an individual's emotional and psychosocial well-being. AIMS: Assess safety and tolerability of a combination of microdermabrasion (DG) procedures using a novel brightening pro-infusion serum (EC-DG) with a targeted at-home treatment regimen in subjects with mild to severe facial hyperpigmentation, including melasma, post-inflammatory hyperpigmentation, and dark spots. PATIENTS/METHODS: This 12-week, open-label study enrolled 18 subjects (Fitzpatrick skin types I-IV) who underwent 6 in-office DG procedures with EC-DG (one procedure administered biweekly), along with daily topical application of a brightening treatment serum and dark spot cream. End points included change from baseline across multiple skin quality attributes and the Melasma Area and Severity Index (MASI), self-assessment questionnaires, and tolerability assessments. RESULTS: The combination treatment was well tolerated and resulted in significant (p ≤ 0.05) improvements from baseline in radiance, tactile roughness, and moisturization/hydration immediately after the first treatment, in MASI score at day 3, and in overall hyperpigmentation at week 4. Most (94.1%) subjects were satisfied with treatment. CONCLUSIONS: DG procedures using EC-DG combined with a targeted at-home skincare regimen are effective and tolerable for treating facial hyperpigmentation across a broad range of skin types.

Skin-lightening products and Jordanian women: Beliefs and practice. A cross-sectional study.

BACKGROUND: The use of skin-lightening products (SLPs) among Jordanian women has immensely increased and healthcare professionals have a vital role in raising public awareness of SLPs. The aim of this study is to identify SLPs practices among Jordanian women and their basic knowledge of the agents and the side effects associated with using these products. METHODS: A cross-sectional study conducted during October to December of 2022. Jordanian women above 18 years of age were invited to participate via a survey link. Descriptive statistics were used, and logistic regression was applied to screen for variables affecting the knowledge score of the participants. RESULTS: The mean age of the study participants (n = 384) was 32.04 (SD = 12.678). Results demonstrated that more than half of the participants (n = 193) reported current or past use of SLPs. Additionally, less than one-fifth (18.2%) of the participants (n = 70) reported previously experiencing some side-effects after using SLPs. About 90% of participants thought that these side-effects were caused by the active ingredients in SLPs. Most of the participants were able to identify some of the active ingredients used in SLPs such as Vitamin C (87.8%) and Hydroquinone (62.0%). It was also found that young participants, and those employed, or university students had higher knowledge scores of SLPs' active ingredients, and of their side-effects. CONCLUSION: This study demonstrated that Jordanian women are adequately informed about skin-lightening products. Moreover, the practices revealed an educated pattern of action when obtaining information regarding SLPs. Fundamentally, healthcare providers should be influential in educating consumers on the proper use. Strict guidelines and policies should target the practices concerned with these products.

Knowledge, perceptions, practices, promotive factors, and health risks awareness of African Basotho women towards skin lightening products: a cross-sectional survey.

Introduction: the use of skin lightening products (SLPs) by women is poorly documented in Africa, with statistics from some countries entirely missing. This study assessed knowledge, perceptions, practices and factors associated with health risk awareness of African Basotho women towards SLPs. Methods: this was a questionnaire-based cross-sectional study based on convenience sampling of females in secondary/high schools, universities, factories and business offices in Maseru City, Lesotho. Analysis of the differences in knowledge (adequate ≥50% score), perceptions, and practices between four participant groups was based on ANOVA, p<0.05. Associations between sociodemographic variables and the use of SLPs were performed using logistic regression model in SPSS version 27. Results: a total of 468 participants out of 496 responders qualified for data analysis based on predefined data cleaning criteria. Knowledge about SLPs was adequate (78.2%, n=468). By proportion, the main sources of the SLPs were supermarkets (67.6%, n=183) and pharmacy stores (41.9%). About 43.7% (n=468) of the participants used SLPs, with the factory workers mostly associated with SLPs use (aOR: 2.91, 95% CI 1.15-7.40; p=0.02). The majority (53.4%, n=131) of users had inadequate knowledge about the link between skin lightening and skin problems. The most common reasons for use of SLPs were rash (pimples, blemishes) (43.9%, n=107), dry skin (41.1%) and skin reddening (33.6%). Conclusion: there was adequate knowledge and moderate practice of skin lightening among African Basotho women. Public awareness campaigns and strict regulations are required to address the problem of SLPs use.

Potential application of natural bioactive compounds as skin-whitening agents: A review.

BACKGROUND: Melanin is a skin pigment that gives color to the skin, hair, and eyes. The accumulation or over production of melanin can lead to aesthetic problems as well as serious diseases associated with hyperpigmentation. Skin lightening is described as the procedure of using natural or synthetic products to lighten the skin tone or provide an even skin complexion by reducing the amount of melanin in the skin; therefore, skin lightening products help people to treat their skin problems. Ingredients such as hydroquinone, ascorbic acid, and retinoic acid were used as whitening agents to lighten the skin. However, they have many adverse effects on the skin and body health, such as skin irritation. AIM: In this review, firstly, discuss on the directly/indirectly target melanogenesis-related signal pathways. Secondly, summarize potential natural bioactive ingredients with skin lightening properties from plants, marine organisms, microorganisms. Finally, the remaining problems and future challenges are also discussed. METHODS: For relevant literature, a literature search was conducted using Google Scholar and Web of Science. Natural bioactive compounds, tyrosinase inhibitors, and other related topics were researched and evaluated. RESULTS: Natural products isolated from plant and animal resources are potential active cosmetic candidates for lightening the skin tone and skin whitening and protection against UV irradiation. Natural bioactive ingredients as cosmetic whitening additives have attracted increasingly attention due to their safety and cost effectiveness, with few side effects. CONCLUSION: Although natural active substances have been advocated for use in whitening cosmetics in recent years, there are still many challenges due to the fact that traditional inhibitors are used perennial in cosmetics which cannot be easily changed and the research on natural active substances is still in its infancy. In the future, by improving the extraction technique of natural extracts, it is achieved to give a qualitative and quantitative analysis of the active ingredients of the extracts, to determine the effect of the active components of action, and to find the substances that have the best possible whitening effect in natural organisms.

Public interest in skin lightening across the United States, January 2015-December 2020.

Skin lightening is a popular practice across the world, especially in India, the Philippines and other Asian countries, and some Caribbean nations. It is a dangerous trend, as some of the products used to achieve a lighter skin tone have been shown to often contain unsafe chemicals. In this article, we examine trends in consumer interest in skin lightening using a Google Trends query of 4 search terms: "skin lightening," "skin brightening," "skin whitening," and "skin bleaching," across the United States from 2015 to 2020, and demonstrated that it is most popular in states with diverse populations, including a high percentage of black and Asian Americans.

Cosmetic skin lightening use and side effects.

Cosmetic skin lightening is a growing dermatologic public health problem that affects communities of color worldwide. Despite well-documented adverse health effects, cosmetic skin lightening continues to be a popular practice among patients of color. Given the US's changing demographics, it is critical for dermatologists to be knowledgeable about the medical impact as well as social and cultural implications of this practice. This review article aims to serve as a primer for the dermatologist on the medical and sociocultural aspects of cosmetic skin lightening, as well as an approach to discuss the issue of cosmetic skin lightening with patients. We conducted a comprehensive PubMed search using the terms 'skin lightening agents,' 'skin bleaching,' and 'depigmenting agents,' and reviewed the literature on cosmetic skin lightening products, active ingredients, and adverse side effects. Herein, we review the prevalence, ingredients, and health implications of cosmetic skin lightening products. We also provide recommendations for counseling patients who practice cosmetic skin lightening in a culturally sensitive manner.

Skin lightening: causes and complications.

Skin bleaching, also known as skin lightening, is the deliberate lightening of an individual's skin tone without medical supervision. The causes are complex, multifactorial and often intertwined, although the unifying themes centre around a belief that lighter skin denotes an individual of higher status, socioeconomic background or physical beauty, than their darker-skinned counterpart. Skin lightening is achieved using agents that block the production of melanin and often contain drugs such as hydroquinone, superpotent topical steroids or mercury. These drugs can cause serious local and systemic complication. Skin-lightening compounds are illegal in most countries throughout the world; however the industry is worth billions of dollars annually, and the agents can be easily obtained by individuals seeking to lighten their skin. Dermatologists are in a unique position to identify those at risk of using skin-bleaching agents, manage complications and give advice on the physiological variation in pigmentation and how to avoid using skin-lightening agents to treat dermatological conditions. To manage the belief that lighter skin is better, societal level change is required to ensure that people of all skin tones are represented in the media.

Parallel discourses: leveraging the Black Lives Matter movement to fight colorism and skin bleaching practices.

OBJECTIVES: The 'Black Lives Matter' (BLM) movement in 2020 exemplifies efforts to counter prejudices and the colourist narrative. Harmful use of topical skin lightening agents continues worldwide despite interdiction or restricted use under domestic, European and international regulations. STUDY DESIGN: Commentary. METHODS: Narrative review. RESULTS: In this Short Communication, we consider the significance of societal perspectives of skin colour, glocalized whiteness, efforts to attain self-esteem and social mobility through skin lightening practices, and the role of cosmetic products in fuelling this phenomenon. CONCLUSIONS: Addressing the inadvertent (or indeed conscious) vehicles of systematic racism and sustaining of skin colour prejudices and stereotypes of fair skin beauty by cosmetic companies is warranted. Targeted health messaging is an imperative.

[Topical treatment of pigmentation disorders with cosmetic and pharmaceutical agents]. / Topische Behandlung von Pigmentstörungen mit kosmetischen und pharmazeutischen Wirkstoffen.

BACKGROUND: Esthetically unattractive hyperpigmentation can occur post-inflammatory or as a result of genetic or hormonal influences, UV exposure or medication. Important parameters for the quality of topical treatments are evidence-based in vivo and in vitro efficacy as well as scientifically verified wanted and unwanted effects. OBJECTIVES: This paper will present cosmetic and pharmaceutical topical ingredients against hyperpigmentation that have been proven in scientific studies. MATERIALS AND METHODS: A search of PubMed database was performed in October 2020 using the various ingredient names, "melasma" and "hyperpigmentation." Two reviewers independently screened titles, leading to the selection of 30 papers. RESULTS: Hydroquinone, a tyrosinase inhibitor, has been used for over 40 years to treat hyperpigmentation. It is the most commonly studied agent for lightening pigment. Despite the limited evidence-based research on novel treatment approaches, several ingredients did show efficacy as depigmenting agents, including tyrosinase inhibitors, substances that increase cell turnover, and plant derivatives. CONCLUSIONS: Hydroquinone is still the gold standard for the treatment of hyperpigmentation, along with the triple therapy of hydrochinon, tretinoin, and steroids in different modifications. In summary, hyperpigmentation is best treated using a combination therapy of different approaches that includes consequent UV protection.