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.

The Therapeutic Use of Antioxidants for Melasma.

Melasma is a chronic dermatologic condition with an incompletely understood pathogenesis and well-demonstrated impact on patient quality of life. Melasma is a common cause for seeking dermatologic care, and with no universally efficacious therapy or cure, com-bination treatment is the best approach for many cases. Numerous studies have demonstrated the role of oxidative stress in patients with melasma, prompting investigation into several antioxidants for melasma therapy. In this review, we discuss the well-defined role of oxidative stress in melasma and the therapeutic efficacy of various antioxidants for patients suffering from melasma. We focus our discussion on studies investigating the role of vitamin C, azelaic acid, cysteamine, glutathione, carotenoids, and numerous other antioxidants in disorders of hyperpigmentation. There is promising evidence for the use of these antioxidants, as topical, oral, and intra-venous preparations, both in isolation and in conjunction with other melasma therapies. J Drugs Dermatol. 2020;19(8):788-792. doi:10.36849/JDD.2020.5079.

Nephrotic syndrome caused by exposures to skin-lightening cosmetic products containing inorganic mercury.

Introduction: Mercury has long been prohibited for use in skin-lightening agents, but such products are still widely available in many parts of the world.Objective: To evaluate the characteristics of subjects with nephrotic syndrome caused by exposures to skin-lightening products containing mercury and the impact of treatments with chelation agents and/or steroids on the time to achieve remission of proteinuria and normal urine mercury concentrations.Methods: We searched Medline and Embase (1971-31 March 2019), Google Scholar (2001-March 2019) and WanFang Data (1999-March 2019), using mercury, mercury poisoning, cosmetics, skin-lightening and nephrotic syndrome as search terms. Affected subjects must have had nephrotic range proteinuria and a renal biopsy performed. The searches revealed 46 citations, but 32 were excluded because of a doubtful history, incomplete data collection, more than one source of mercury exposures, non-nephrotic proteinuria, treatments by herbal medicines and duplicate articles. The 14 remaining reports describing 30 cases formed the basis of this review.Incidence and geographical origins: There was an obvious increase in the number of reports with more complete information from Asia (n = 13) and Europe (n = 1) during 2002-2006 (n = 3) and 2010-2017 (n = 11), involving 3 subjects in 2002-2006 and 27 subjects in 2010-2017.Characteristics of subjects: All 30 subjects were Asian females, mostly aged 18-52 years (median 34 years). Nephrotic syndrome occurred 1-60 months (median 5 months) after exposures to mercury. The proteinuria was heavy (urinary protein excretion 3.2-20.7 g/day, median 5.7 g/day). Other features of mercury toxicity were generally absent. Blood mercury concentrations were normal in 6 subjects and 1.1-10.9 times (median 3.5 times) the upper limit of normal in 14 subjects. Urine mercury concentrations were much higher in 24 subjects, at 1.2-94.6 times (median 9.8 times) the upper limit of normal. Renal biopsy typically revealed minimal change disease (67%) or membranous nephropathy (23%).Etiological importance of mercury: Several clinical observations strongly support the etiological importance of mercury, including a positive relationship between body mercury burden (24-h urine mercury excretion) and severity of proteinuria, the parallel (often proportional) reductions in body mercury burden and proteinuria after cessation of exposures and initiation of chelation therapy and the risk of persistent proteinuria in subjects not treated with chelating agents.Natural history and impact of specific treatments: Spontaneous recovery (within 1.5 months) of mercury-induced nephrotic syndrome was rare.Twenty-three subjects were treated with chelating agents (n = 7) or chelating agents plus steroids (n = 16). There was relatively clear information on the time to remission of proteinuria (urine protein <150 mg/day) in nine subjects following chelation therapy (n = 5) or chelation therapy plus steroids (n = 4) (median 2 months, range 1-9 months). In comparison, the time to remission was longer in three subjects not treated with chelation therapy (≥12 months). There were fewer reports with relatively clear information on the time to achieve normal urine mercury concentrations (<35 nmol/day, <50 nmol/L or <5.0 nmol/mmol creatinine). In four subjects with treatment by chelating agents (n = 1) or chelating agents plus steroids (n = 3), this took 9-16 months (mean ∼11 months). The adjunctive role of steroids in mercury-induced nephrotic syndrome was unclear.Conclusions: Repeated exposures to inorganic mercury in skin-lightening cosmetic products typically cause minimal change disease or membranous nephropathy, resulting in nephrotic syndrome. Apart from cessation of product use, chelation therapy is clearly indicated, in view of the etiological importance of mercury and the presence of increased body burden with target organ damage. The optimal dosages and treatment strategies for unithiol (2,3-dimercapto-1-propanesulfonic acid) and succimer (dimercaptosuccinic acid) have yet to be determined.

["Getting clear skin and why not?": voluntary depigmentation among women in a southwest region of Benin]. / "Avoir la peau claire et pourquoi pas? ": dépigmentation volontaire chez les femmes dans une région du sud-ouest du Bénin.

INTRODUCTION: This study aims to determine the prevalence and the factors associated with the use of products for voluntary depigmentation among women aged 15-49 years in Comè health zone in Benin. METHODS: We conducted a cross-sectional study of 511 women aged 15-49 years selected using a cluster survey in 2016. Data were collected using a questionnaire seeking to explore the demographic, socio-cultural and economic characteristics of women. Depigmentation ingredients have been identified looking at the composition of regularly used body lotions. We performed a multiple logistic regression analysis. The statistical significance level was set at 5%. RESULTS: The prevalence of use for voluntary depigmentation products among women aged 15-49 years in Comè health zone was 79,22% 95%; CI=[75,72-82,78] and 84,23% of women knew at least one of the adverse health effects associated with the use of skin depigmentation products. The products used were hydroquinone based (98.24%) and dermocorticoid based (1.76%). Factors associated with the use of voluntary depigmentation products included marital status (single, widowed, separated or divorced) (OR=3.1; 95% CI=[1.29-7.44]), the search for a husband or a partner (OR=4.92; 95% CI=[1.20-20.09]), the presence of hyperpigmented spots (OR=10.32; 95% CI=[2.87-37,01]). CONCLUSION: These results show that the use of skin depigmentation products among women is a serious and huge public health problem in Comè health zone. Integrated communication campaign which can produce positive changes should be implemented.

The color of skin: psychiatric ramifications.

Skin color is one of the major attributes that defines both individual distinctiveness and differences between groups. There is a preference for lighter skin world-wide, among both light- and dark-skinned individuals, further leading to skin-color bias based upon skin-color hierarchy within certain ethnoracial groups. The psychiatric and psychosocial ramifications of skin color are important in several situations, including (1) disorders of skin discoloration (eg, vitiligo), which can significantly affect the psychosocial development of the patient especially when it has its first onset during adolescence; (2) widespread use of skin-lightening products, which are used despite knowledge about serious toxicity from inorganic mercury and potent corticosteroids that are some of their main constituents; (3) indoor tanning, which is a recognized carcinogen and practiced by over 50% of university-age adults and 20% of adolescents. Educating about photocarcinogenicity does not change tanning behaviors, which is strongly driven by peer pressure; and (4) when a psychiatric disorder, such as body dysmorphic disorder or major depressive disorder, is the primary basis for skin color dissatisfaction. Despite the role of complex sociocultural and psychiatric factors in clinical manifestations involving skin color, a supportive relation with the dermatologist can significantly aid the patient in managing their disease burden.

The color of skin: white diseases of the skin, nails, and mucosa.

White diseases are a heterogenous group characterized by hypopigmentation or depigmentation. Skin and eye color are determined by the number and size of melanosomes present. Melanin is produced by melanosomes in the melanocytes present within the epidermis of the skin, uvea, and retinal pigmented epithelium (RPE). Conditions altering the number of melanocytes or concentration of melanin result in a lack of pigmentation, appearing as "white diseases" ranging from the well-known albinism and vitiligo to more esoteric white hand syndrome and Degos disease.

[What's new in clinical dermatology?] / Quoi de neuf en dermatologie clinique?

In this article, we performed a review of all new data of clinical relevance for the dermatologists that were published in the medical literature between September, 2017 and September, 2018. Besides advances that will be useful in day-to-day dermatological practice, we intended to give a more general perspective to this review by taking into account certain international health issues that might in final concern each of us in a globalized world. Focus were more particularly done on the following topics: infectious diseases (including sexually transmitted infections), neglected tropical diseases, adverse effects of drugs, bullous diseases, allergology, wound healing, dermatology on black skin, and public health dermatology.

Melanogenesis Inhibitors from the Rhizoma of Ligusticum Sinense in B16-F10 Melanoma Cells In Vitro and Zebrafish In Vivo.

The rhizoma of Ligusticum sinense, a Chinese medicinal plant, has long been used as a cosmetic for the whitening and hydrating of the skin in ancient China. In order to investigate the antimelanogenic components of the rhizoma of L. sinense, we performed an antimelanogenesis assay-guided purification using semi-preparative HPLC accompanied with spectroscopic analysis to determine the active components. Based on the bioassay-guided method, 24 compounds were isolated and identified from the ethyl acetate layer of methanolic extracts of L. sinense, and among these, 5-[3-(4-hydroxy-3-methoxyphenyl)allyl]ferulic acid (1) and cis-4-pentylcyclohex-3-ene-1,2-diol (2) were new compounds. All the pure isolates were subjected to antimelanogenesis assay using murine melanoma B16-F10 cells. Compound 1 and (3S,3aR)-neocnidilide (8) exhibited antimelanogenesis activities with IC50 values of 78.9 and 31.1 µM, respectively, without obvious cytotoxicity. Further investigation showed that compound 8 demonstrated significant anti-pigmentation activity on zebrafish embryos (10‒20 µM) compared to arbutin (20 µM), and without any cytotoxicity against normal human epidermal keratinocytes. These findings suggest that (3S,3aR)-neocnidilide (8) is a potent antimelanogenic and non-cytotoxic natural compound and may be developed potentially as a skin-whitening agent for cosmetic uses.

Skin lighteners and hair relaxers as risk factors for breast cancer: results from the Ghana breast health study.

Skin lighteners and hair relaxers, both common among women of African descent, have been suggested as possibly affecting breast cancer risk. In Accra and Kumasi, Ghana, we collected detailed information on usage patterns of both exposures among 1131 invasive breast cancer cases and 2106 population controls. Multivariate analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for breast cancer risk factors. Control usage was 25.8% for ever use of skin lighteners and 90.0% for use of hair relaxers for >1 year. The OR for skin lighteners was 1.10 (95% CI 0.93-1.32), with higher risks for former (1.21, 0.98-1.50) than current (0.96, 0.74-1.24) users. No significant dose-response relations were seen by duration, age at first use or frequency of use. In contrast, an OR of 1.58 (95% CI 1.15-2.18) was associated with use of hair relaxers, with higher risks for former (2.22, 1.56-3.16) than current (1.39, 1.00-1.93) users. Although numbers of burns were inconsistently related to risk, associations increased with duration of use, restricted to women who predominately used non-lye products (P for trend < 0.01). This was most pronounced among women with few children and those with smaller tumors, suggesting a possible role for other unmeasured lifestyle factors. This study does not implicate a substantial role for skin lighteners as breast cancer risk factors, but the findings regarding hair relaxers were less reassuring. The effects of skin lighteners and hair relaxers on breast cancer should continue to be monitored, especially given some biologic plausibility for their affecting risk.

[Squamous cell carcinoma associated with use of skin-lightening cream]. / Carcinome épidermoïde associé à une dépigmentation volontaire.

BACKGROUND: Women widely use skin-lightening products for cosmetic purposes in sub-Saharan Africa despite numerous reported cutaneous and systemic complications. The occurrence of epidermoid carcinoma has long been reported, but only three cases have been published so far. We report the first case in Mali. PATIENTS AND METHODS: A 30-year old woman with no noteworthy medical history was seen at our outpatient center for cervical ulceration that had been present for the last 5 years. She had used cosmetic bleaching cream over a period of around ten years. Physical examination revealed extensive ulceration on the left side of her neck. Blood tests for viral hepatitis and human immunodeficiency virus were negative. The pathological examination of the skin biopsy confirmed the diagnosis of squamous cell carcinoma. After failure of the initial excision with early relapse, multiple surgical ablations were performed 3 months later. DISCUSSION: The high prevalence of skin-lightening cosmetic use contrasts with the rarity of epidermoid carcinoma in depigmented skin. However, a large chronic ulcer on uncovered parts of the upper body, particularly the neck, should prompt physicians to consider skin cancer. Appropriate preventive measures include the promotion of educational messages for the general population, the use of sun-protection devices, and routine skin biopsy for all women presenting chronic cervical ulceration after long-term use of skin-lightening products.

Assessment of radical scavenging, whitening and moisture retention activities of Panax ginseng berry mediated gold nanoparticles as safe and efficient novel cosmetic material.

Panax ginseng berry extract possess remarkable pharmacological effects on skin treatment such as anti-aging, antioxidant, promotor of collagen synthesis and alleviation against atopic dermatitis. In recent years, gold nanoparticles have gained much attention due to their extensive range of applications in particular in the field of drug delivery as a result of their biological compatibility and low toxicity. In a previous study, we designed and developed biocompatible gold and silver nanoparticles based on phytochemical profile and pharmacological efficacy of P. ginseng berry extract, we were able to reduce gold ions to nanoparticles through the process of green synthesis. However, its potential as a cosmetic ingredient is still unexplored. The aim of the present study is to investigate the moisture retention, in-vitro scavenging and whitening properties of gold nanoparticles synthesized from P. ginseng berry in cosmetic applications. Our findings confirm that P. ginseng berry mediated gold nanoparticles exhibited moisture retention capacity. In addition, MTT assay results confirmed that P. ginseng berry mediated gold nanoparticles are non-toxic to human dermal fibroblast and murine melanoma skin cells, possess scavenging activity, protect and provide alleviation against injured caused by H2O2-induced damage. In addition, P. ginseng berry mediated gold nanoparticles, significantly reduced melanin content and suppress tyrosinase activity in α-MSH-stimulated B16BL6 cells. We conclude that P. ginseng berry mediated gold nanoparticles are biocompatible and environmental affable materials and can be a potential novel cosmetic ingredient.

Cutaneous squamous cell carcinomas (SCC) associated with cosmetic skin whitening: 8 cases reported in Senegal.

BACKGROUND: The cosmetic use of bleaching products is common among women from sub-Saharan Africa. The most frequently used products are highly potent corticosteroids (clobetasol propionate) and hydroquinone. Herein, we report 8 cases of SCC in women using skin bleaching products for cosmetic purposes. Our aim is to describe the epidemiological, clinical and pathological aspects of the carcinomas observed during the course of skin lightening. METHODS: We conducted a descriptive multicentre study from August 2005 to January 2016 in three dermatology units in Senegal. We included all patients consulting for cutaneous squamous cell carcinoma associated with skin bleaching. Sociodemographic, clinical, paraclinical and therapeutic data were recorded. RESULTS: A total of 8 female patients were included. The mean age was 48.1 years (37-63 years). Topical hydroquinone and highly potent corticosteroids were the main products used over the whole body, for an average duration of 20.3 years. No pre-neoplastic skin disease was found in our patients. The clinical aspects of tumours were as follows: cauliflower-like (n=4), ulcerated (n=3) and nodular (n=1). The average development time before consultation was 6.75 months. All the cutaneous squamous cell carcinomas were localized to lichenoid lesions or exogenous ochronotic lesions on photo-exposed areas: face (n=1), neck (n=3) or upper back (n=4). The most common histopathological type was the infiltrating form and there was one case of in situ carcinoma. The outcome was favourable in six of eight patients after surgical resection. Two deaths occurred: one through tumour recurrence and the other through haemorrhagic shock. CONCLUSIONS: From 2005 to 2016, eight cases of cutaneous squamous cell carcinomas associated with cosmetic use of bleaching products were reported in Senegal. The mechanism was not fully elucidated and further studies are necessary. These observations provide an additional argument for combating this practice and including skin bleaching among known risk factors for squamous cell carcinoma.

A Prospective Trial Comparing Q-Switched Ruby Laser and a Triple Combination Skin-Lightening Cream in the Treatment of Solar Lentigines.

BACKGROUND: Quality-switched (QS) laser therapy is a safe and well-established treatment option for removing solar lentigines. Triple combination therapy (TCT) with the active pharmaceutical ingredients hydroquinone 5%, tretinoin 0.03%, and dexamethasone 0.03% is often used for skin-lightening. OBJECTIVE: This prospective, open-label trial compares the efficacy and safety of a QS Ruby laser (QSRL) and a TCT in the treatment of solar lentigines. METHODS: In total, 15 patients with symmetrically distributed solar lentigines on the back of both hands were included. The lesions on the back of the right hand were treated in one or 2 sessions with a QSRL, the ones on the back of the left hand with a TCT for 7 weeks accompanied by UV protection. Clinical results were evaluated 4 weeks, 8 weeks, and 20 weeks after baseline. RESULTS: Treatment with QSRL provided significant lightening (p = .01) compared with TCT. Both procedures were generally well-tolerated. Comparing the side effects, the laser produced significantly more crusting and hyperpigmentation than the TCT. CONCLUSION: Both QSRL and TCT were capable in reducing solar lentigines in Fitzpatrick skin Type I to IV with an acceptable side effect profile. The QSRL provides faster, superior, and long lasting lightening compared with TCT.