Best practices in the treatment of melasma with a focus on patients with skin of color.

BACKGROUND: Melasma is a chronic hypermelanosis of the skin that affects approximately 1% of the global population, predominantly affects women, and is more prevalent in skin of color. Melasma is a common driver for patients with skin of color to seek out a dermatologist for treatment, and ensuring the right approach for these patients is important because some treatments may be associated with adverse side effects. Because of the chronicity of the disease and established psychosocial and emotional impacts, there is a large need to ensure care follows the best available evidence on the treatment of patients with melasma. OBJECTIVE: Here, we summarized current available topical treatments for melasma with considerations dermatologists should have for their patients with skin of color. METHODS: Steering committee consensus on clinical best practices. RESULTS: We describe a flexible and focused treatment algorithm that reflects both treatment and maintenance periods that is a consensus of our extensive clinical experience. LIMITATIONS: Use of real-world evidence and potential for individual practice bias. CONCLUSION: Melasma can be challenging to treat, particularly in patients with skin of color, and our recommendations for best practices for patients in the United States are an important step toward standardizing care.

Integrating skin color assessments into clinical practice and research: A review of current approaches.

Skin color classification can have importance in skin health, pigmentary disorders, and oncologic condition assessments. It is also critical for evaluating disease course and response to a variety of therapeutic interventions and aids in accurate classification of participants in clinical research studies. A panel of dermatologists conducted a literature review to assess the strengths and limitations of existing classification scales, as well as to compare their preferences and utilities. We identified 17 skin classification systems utilized in dermatologic settings. These systems include a range of parameters such as UV light reactivity, race, ethnicity, and degree of pigmentation. The Fitzpatrick skin type classification is most widely used and validated. However it has numerous limitations including its conflation with race, ethnicity, and skin color. There is a lack of validation data available for the remaining scales. There are significant deficiencies in current skin classification instruments. Consensus-based initiatives to drive the development of validated and reliable tools are critically needed.

Racial and Ethnic Diversity in Vitiligo Clinical Trials: A Retrospective Cross-Sectional Study Assessing Demographic Reporting of Participants.

BACKGROUND: While the prevalence of vitiligo is similar across racial and ethnic groups, the effects of vitiligo vary by demographic group, culture, and skin color, with darker-skinned individuals facing greater stigma due to increased visibility of the disease.1,2 The recruitment of diverse participants that are representative of the United States (US) population is crucial to ensuring the generalizability of findings and understanding the impacts of vitiligo across diverse patient groups.   Objectives: This study aimed to determine demographic reporting trends in US vitiligo clinical trials and to determine whether participants are representative of the US population. METHODS: A search for US vitiligo clinical trials was conducted on clinicaltrials.gov. Trials conducted between 2006 to September 5, 2023, were included if they intended to treat vitiligo, were conducted in the US, and were completed or terminated.  Results: Of the 15 trials meeting inclusion criteria, only 60% (n=9) reported participant race/ethnicity. These 9 studies included 1,510 participants, of which only 25.43% (n=384) were non-White and 20.40% were Hispanic. There was disproportionately low representation of racial minorities, particularly Black, Native American, and Native Hawaiian groups.   Limitations: Limitations of our study include small sample size, variations in demographic reporting between trials, and undercounting of minority groups by the US Census.  Conclusions: Racial and ethnic minority groups remain underrepresented in US vitiligo clinical trials. Given that the impact of vitiligo can vary by the affected individual’s demographic group and skin color, investigators must be intentional about including a more diverse and representative population in vitiligo clinical trials.  J Drugs Dermatol. 2024;23(7):e164-e166. doi:10.36849/JDD.8117e.

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.

Racial and ethnic disparities in clinical research and the dermatology workforce: Part 2.

Although racial and ethnic demographics are shifting in this country, it is not reflected in the diversity of clinical trial research participants; science, technology, engineering, and mathematics pipeline programs; or the workforce in the field of dermatology. Barriers to recruitment of minority patients for research studies also exist for numerous reasons including lack of education of prospective subjects, lack of awareness of ongoing trials, and mistrust within the health care system. Gaps in the science, technology, engineering, and mathematics pipeline for racial and ethnic minorities, particularly Black, Hispanic/Latinx, and American Indian or Alaska Native, are due in large part to structural racism. Lack of exposure as well as lack of educational, mentorship, and research opportunities contribute to gaps in the dermatology workforce. Having a representative population in the dermatology workforce and in clinical research trial patients is essential for optimum patient care, excellence in the specialty, and knowledge of appropriate treatments for minority populations. This article will discuss knowledge gaps for increasing minority subjects who participate in clinical research trials and discuss mechanisms to engage this community in trial recruitment. Additionally, this article addresses lack of racial and ethnic diversity of the dermatology workforce and performance gaps in the recruitment of racial/ethnic minorities into dermatology.

Gaps in medical education curricula on skin of color in medical school, residency, and beyond: Part 1.

Various studies have revealed a disproportionately low representation of skin of color (SOC) dermatology in the medical education system of the United States. This disparity contributes to adverse experiences, missed and/or delayed diagnoses, and overall health inequities for individuals of color. The lack of sufficient SOC education begins at the medical school level and continues throughout residency, fellowship, and beyond formal training. This lack of education can be seen in the dearth of images of common and uncommon skin conditions in darker skin in widely used textbooks and educational resources as well as in the lack of formal training in SOC in many residency programs. Thus far, there have been valuable strides to make dermatologic education more inclusive of all skin colors, but there remains significant work to be done. With the population of the United States expected to continue to diversify and with the expectation that SOC will be a trait of over half of the population of the United States by 2050, it is important to strive for health equity by ensuring that comprehensive and inclusive medical training incorporates SOC. This paper will explore the issue of gaps in medical education in SOC dermatology at all levels and offer a strategic call to action to aid in rectifying this situation.

Treatment recommendations for acne-associated hyperpigmentation: Results of the Delphi consensus process and a literature review.

Acne vulgaris can be associated with hyperpigmentation, particularly in individuals with skin of color. This acne-induced macular hyperpigmentation (AMH), also called postinflammatory hyperpigmentation, is often long lasting and negatively impacts quality of life. Large-scale, randomized, controlled clinical trials with regard to the treatment of acne and AMH are lacking. For this reason, evidence-based treatment recommendations cannot be made. However, AMH is a common condition, and it is important for clinicians to have guidance on management strategies. The authors, a group of 10 board-certified dermatologists, conducted a modified Delphi consensus process to reach a consensus on first-line therapy for AMH and determine whether therapeutic choices change in different patient subgroups. We reached a consensus that most patients with acne and AMH should receive early and efficacious acne treatment with a topical retinoid and benzoyl peroxide. Therapies aimed at addressing AMH-including hydroquinone, azelaic acid, chemical peel, or antioxidants-may also be considered for enhancing the effect of the treatment regimen on acne and pigmentation. Chemical peels may be used as adjunctive or second-line therapy. This article details the results of the Delphi process, reviews relevant literature for providing recommendations for AMH, and discusses appropriate treatment options.

Radiofrequency and Radiofrequency Microneedling in Skin of Color: A Review of Usage, Safety, and Efficacy.

BACKGROUND: Radiofrequency (RF) and radiofrequency microneedling (RFM) for rhytides, scarring, and skin rejuvenation are believed to have a lower risk of postprocedural dyspigmentation in darker skin types. OBJECTIVE: To explore the safety and efficacy of RF and RFM in Fitzpatrick skin Types III to VI. METHODS AND MATERIALS: A systematic review of PubMed/MEDLINE databases from 2000 to 2021 using combinations of the terms radiofrequency, microneedling, skin of color, and Fitzpatrick was performed. Exclusion criteria included non-Fitzpatrick skin Types III-VI patient population, nonprimary articles, nonskin radiofrequency, and nonhuman studies. RESULTS: Thirty-five articles addressing the use of RF or RFM in skin of color were identified-22 for skin rejuvenation, 7 for acne scars, 4 for nonacne scars, 1 for hyperpigmentation, and 1 for acne treatment. Seven studies noted transient postinflammatory hyperpigmentation, 1 observed mild prolonged hyperpigmentation, and only 1 study reported permanent scarring. CONCLUSION: Radiofrequency and RFM seem to have a low risk of scarring or hyperpigmentation in skin of color. This review demonstrates that these procedures have been successfully used primarily for rhytides, acne scarring, and skin rejuvenation. However, a large proportion of the studies lack strong quality evidence.

Pigmented Basal Cell Carcinoma: An Argument for Sub-Classification.

Basal cell carcinoma (BCC) has several subclassifications, including pigmented basal cell carcinoma. In our clinical experience, we have found that pigmented basal cell carcinoma itself has multiple subtypes which can overlap with traditional basal cell carcinoma subclassifications. In this letter, we argue for the subclassification of pigmented basal cell carcinoma, as either superficial, nodular, or morpheaform. We believe further subclassification of pigmented BCCs may reveal important therapeutic and prognostic differences which could make an impact on the morbidity and mortality of this condition for those affected, many of whom are skin of color patients that are already disproportionately affected by health disparities related to skin cancer. J Drugs Dermatol. 2023;22(2): 217-218. doi:10.36849/JDD.6883.

Rising Interest in Sunscreen for Skin of Color: An Analysis of Google Trends.

Syder NC, Elbuluk N. rising interest in sunscreen for skin of color: an analysis of Google trends. J Drugs Dermatol. 2023;22(7):712-713. doi:10.36849/JDD.7373.

Variations in genetics, biology, and phenotype of cutaneous disorders in skin of color. Part II: Differences in clinical presentation and disparities in cutaneous disorders in skin of color.

Skin of color (SOC) patients are projected to comprise the majority of the population by 2044, yet knowledge gaps in the clinical presentation and treatment of both common and uncommon dermatologic conditions in skin of color persist. Improved awareness of disparities that disproportionately impact SOC patients is necessary to address health inequity in the field of dermatology. The first part of this CME discussed structural, genetic, and immunophenotypic differences in SOC in common inflammatory disorders as well as cutaneous malignancies. The second part of this CME highlights clinical differences in the phenotypic presentation of the inflammatory disorders of atopic dermatitis, psoriasis, and hidradenitis suppurativa as well as the cutaneous malignancies of melanoma, basal cell carcinoma, and cutaneous T-cell lymphoma. Health disparities associated with each of these conditions are also discussed.

Variations in genetics, biology, and phenotype of cutaneous disorders in skin of color - Part I: Genetic, biologic, and structural differences in skin of color.

Skin of color (SOC) populations include those who identify as Black/African, Hispanic/Latinx, Asian/Pacific Islander, American Indian/Native Alaskan, Indigenous Australian, Middle Eastern, biracial/multiracial, or non-White; this list is far from exhaustive and may vary between and within cultures. Recent genetic and immunological studies have suggested that cutaneous inflammatory disorders (atopic dermatitis, psoriasis, and hidradenitis suppurativa) and malignancies (melanoma, basal cell carcinoma, and cutaneous T-cell lymphoma) may have variations in their immunophenotype among SOC. Additionally, there is growing recognition of the substantial role social determinants of health play in driving health inequalities in SOC communities. It is critically important to understand that social determinants of health often play a larger role than biologic or genetic factors attributed to "race" in health care outcomes. Herein, we describe the structural, genetic, and immunological variations and the potential implications of these variations in populations with SOC. This article underscores the importance of increasing the number of large, robust genetic studies of cutaneous disorders in SOC to create more targeted, effective therapies for this often underserved and understudied population. Part II of this CME will highlight the clinical differences in the phenotypic presentation of and the health disparities associated with the aforementioned cutaneous disorders in SOC.

A Multi-Centered Case-Control Study of Vitiligo Support Groups and Quality of Life.

BACKGROUND: There is limited research on the association between vitiligo support group membership and patient quality of life (QoL). OBJECTIVES: To explore the association between support groups and QoL in those with vitiligo by evaluating and comparing the QoL of vitiligo support group members and non-support group members. METHODS: Support group members (n=135) and non-support group members (n=129) were recruited from the Global Vitiligo Foundation (GVF), and three academic medical centers respectively. Patients completed the Vitiligo-Specific Quality of Life (VitiQoL) instrument and a demographic survey. RESULTS: Mean VitiQoL scores for support group members were higher than non-support group members (48.6 ± 23.6 vs 33.0 ± 23.8; P-value < 0.0001), highlighting more negatively impacted QoL. Support group members were less likely to be undergoing treatment (27.4% vs 53.5%; P-value = <0.0001) and were more likely to report duration of vitiligo for >20 years (38.5% vs 19.4%; P-value = 0.0007). CONCLUSIONS: Vitiligo support group membership is associated with worse QoL. Individuals with vitiligo who have worse QoL, chronic, and/or untreated vitiligo may be more likely to seek out vitiligo support groups. Support group referral should be considered in the therapeutic management of vitiligo, particularly in patients whose QoL is more significantly impacted, who fail or are who are without access to treatment or have longstanding disease. J Drugs Dermatol. 2021;20(6):672-675. doi:10.36849/JDD.5706.

Long term safety, tolerability, and efficacy of intracutaneous zolmitriptan (M207) in the acute treatment of migraine.

OBJECTIVE: To determine the long-term safety and tolerability profile of M207 in the acute treatment of migraine. BACKGROUND: M207 is an investigational microneedle-based system for intracutaneous delivery of zolmitriptan for the treatment of migraine attacks. Following on the positive results of a Phase 2/3 placebo-controlled efficacy study (ZOTRIP), this study was designed to evaluate the safety of this novel product during repeated use for the treatment of migraine attacks. METHODS: In this 6-12 month open-label, multicenter observational study, participants used an eDiary to record headache symptoms and adverse events at specified intervals up to 48 h following treatment of a qualifying attack with M207 3.8 mg (intracutaneous zolmitriptan). Participants underwent clinical evaluations at specified intervals up to 12 months. RESULTS: Among 335 participants who treated ≥1 migraine attack, 257 completed 6 months and 127 completed 1 year of treatment. The most common reason for withdrawal from the study was a low frequency of reported attacks post randomization. Overall, 5963 migraine attacks were treated. Most participants (96%) experienced at least 1 adverse event, the vast majority of which concerned the application site, and > 95% of which were mild. Fifteen participants (4%) withdrew due to adverse events; 4 withdrew due to 7 application site reactions, 6 of which were mild. Participants achieved pain freedom in 2477/5617 (44%) of attacks, most bothersome symptom freedom in 3315/5330 (62%) of attacks, and pain relief 2 h post-dose in 4552/5617 (81%) of attacks. Sustained pain freedom 2-24 h was seen in 1761/4698 (38%) of attacks, and 2-48 h in 1534/4429 (35%) of attacks. CONCLUSIONS: The majority of participants experienced cutaneous adverse reactions such as application site erythema, swelling, and bleeding, and most reactions were scored as mild. These results are consistent with what was observed in the single migraine attack treatment ZOTRIP trial indicating that M207 is well tolerated in the setting of longer-term repeated use. Efficacy findings were also similar to those in the ZOTRIP trial. TRIAL REGISTRATION: Clinicaltrials.gov on September 13, 2017 ( NCT03282227 ).

Comorbid diseases of vitiligo: A 10-year cross-sectional retrospective study of an urban US population.

BACKGROUND: Vitiligo is associated with medical conditions, primarily autoimmune disorders; however, only a few studies in the United States have investigated these associations. OBJECTIVE: Our purpose was to investigate the diseases associated with vitiligo in the New York, New York, population and evaluate if these associations differ by race/ethnicity and sex. METHODS: In this retrospective study, we analyzed data collected from the medical records of 1487 vitiligo patients seen at New York University during a 10-year period. RESULTS: Vitiligo patients had a statistically significant higher prevalence of hypothyroidism, multiple sclerosis, rheumatoid arthritis, idiopathic thrombocytopenic purpura, seronegative arthritis, pernicious anemia, myasthenia gravis, inflammatory bowel disease, lymphoma, and systemic lupus erythematosus. Rates of comorbid autoimmune diseases varied by race and sex. LIMITATIONS: Medical charts did not consistently report race/ethnicity, type of vitiligo, and total body surface area affected. Information from nondermatology medical visits was also included. CONCLUSION: This study revealed multiple new disease associations for vitiligo, including multiple sclerosis, idiopathic thrombocytopenic purpura, and lymphoma, as well as confirmed previously reported associations with other autoimmune diseases, the most common being hypothyroidism followed by rheumatoid arthritis. Associations did vary by race/ethnicity and sex.

Beyond Traditional Treatment: The Importance of Psychosocial Therapy in Vitiligo.

Vitiligo is an acquired depigmentation disorder of the skin. Patients with vitiligo often face a challenging disease course, having to cope with a condition that is known to be physically disfiguring, psychologically devastating, and socially stigmatizing. Although an extensive amount of research has been directed towards the dermatologic treatment of vitiligo, an overall lack of data exists investigating treatment of the psychological and emotional burden of patients with vitiligo. This paper reviews the literature for treatment options in patients with vitiligo that specifically target the psychosocial domain. Despite being limited in quantity, several studies have proven the benefits of adjuvant care in the form of group therapy, cognitive behavioral therapy, and self-help programs. Although preliminary evidence is promising, larger prospective studies are needed to further define the role of these psychosocial interventions before integrating them in a more official capacity into the standard of care for patients with vitiligo. Because of the considerable impact of vitiligo beyond its physical symptoms, dermatologists ought to consider the utility of adjuvant therapies to adequately address impairments in self-esteem, body image, and quality of life in patients with vitiligo. J Drugs Dermatol. 2018;17(6):688-691.

The nuclear factor (erythroid-derived 2)-like 2 (NRF2) antioxidant response promotes melanocyte viability and reduces toxicity of the vitiligo-inducing phenol monobenzone.

Vitiligo, characterised by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterised. We hypothesised that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity. We observed that knockdown of NRF2 or NRF2-regulated antioxidants NQO1 and PRDX6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF2 response following monobenzone exposure and constitutive NRF2 activation reduced monobenzone toxicity, supporting NRF2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF2 response as efficiently. Dimethyl fumarate-mediated NRF2 activation protected normal and vitiligo melanocytes against monobenzone-induced toxicity. Given the contribution of oxidant-antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest.

Microneedling: A Comprehensive Review.

BACKGROUND: Microneedling is a minimally invasive procedure that uses fine needles to puncture the epidermis. The microwounds created stimulate the release of growth factors and induce collagen production. The epidermis remains relatively intact, therefore helping to limit adverse events. The indications for microneedling therapy have grown significantly, and it is becoming a more widely used treatment in dermatology. OBJECTIVE: A comprehensive review of microneedling in human subjects and its applications in dermatology. METHODS AND MATERIALS: A search was performed using PubMed/MEDLINE and Science Direct databases. Search terms included "microneedling," "needling," and "percutaneous collagen induction." All available studies involving human subjects were included in the discussion, with priority given to prospective, randomized trials. RESULTS: Studies demonstrate microneedling efficacy and safety for the treatment of scars, acne, melasma, photodamage, skin rejuvenation, hyperhidrosis and alopecia and for facilitation of transdermal drug delivery. While permanent adverse events are uncommon, transient erythema and postinflammatory hyperpigmentation are more commonly reported. CONCLUSION: Microneedling appears to be an overall effective and safe therapeutic option for numerous dermatologic conditions. Larger and more randomized controlled trials are needed to provide greater data on the use of microneedling for different dermatologic conditions in different skin types.

Disparity in Cutaneous Pigmentary Response to LED vs Halogen Incandescent Visible Light: Results from a Single Center, Investigational Clinical Trial Determining a Minimal Pigmentary Visible Light Dose.

Background: While most of the attention regarding skin pigmentation has focused on the effects of ultraviolet radiation, the cutaneous effects of visible light (400 to 700nm) are rarely reported. OBJECTIVE: The purpose of this study was to investigate the cutaneous pigmentary response to pure visible light irradiation, examine the difference in response to different sources of visible light irradiation, and determine a minimal pigmentary dose of visible light irradiation in melanocompetent subjects with Fitzpatrick skin type III - VI. METHODS: The study was designed as a single arm, non-blinded, split-side dual intervention study in which subjects underwent visible light irradiation using LED and halogen incandescent light sources delivered at a fluence of 0.14 Watts/cm2 with incremental dose progression from 20 J/cm2 to 320 J/cm2. Pigmentation was assessed by clinical examination, cross-polarized digital photography, and analytic colorimetry. RESULTS: Immediate, dose-responsive pigment darkening was seen with LED light exposure in 80% of subjects, beginning at 60 Joules. No pigmentary changes were seen with halogen incandescent light exposure at any dose in any subject. CONCLUSION: This study is the first to report a distinct difference in cutaneous pigmentary response to different sources of visible light, and the first to demonstrate cutaneous pigment darkening from visible LED light exposure. Our findings raise the concern that our increasing daily artificial light surroundings may have clandestine effects on skin biology.

J Drugs Dermatol. 2017;16(11):1105-1110.