The Gut and Skin Microbiome in Alopecia: Associations and Interventions.

Objective: This review examines the current literature on the gut-skin connection in alopecia and summarizes interventions that impact hair growth by modulation of the gut or skin microbiome. Methods: PubMed searches were done to assess studies of the gut and skin microbiome and forms of alopecia including, alopecia areata (AA), androgenic alopecia (AGA), alopecia universalis (AU), central centrifugal cicatricial alopecia (CCCA) and lichen planopilaris (LPP). Filters were applied for human and animal studies. Articles not translated to English and studies assessing supplemental therapies on alopecia were excluded. Results: There is evidence that scalp, hair follicle, and gut microbiome alterations are associated with various types of alopecia. There is potential in the use of interventions targeting microbiome dysbiosis, including fecal transplants and probiotics. Limitations: This field of study still requires more high-quality research and studies with larger participant populations. Conclusion: Dysbiosis on the scalp, within the hair follicle and the gut seem to have a role in the pathophysiology of various forms of alopecia. There is evidence that interventions targeting dysbiosis may have potential in the treatment and management of hair loss. Further studies are needed to establish a direct connection and to clarify specific effects of these interventions.

Treatment of Frontal Fibrosing Alopecia in Black Patients: A Systematic Review.

Frontal fibrosing alopecia (FFA) is a progressive cicatricial alopecia that can affect patients with skin of color (SOC); however, patients with SOC often are underrepresented in clinical trials and scientific publications on FFA. To better understand the management of FFA in patients with SOC, we sought to assess the clinical evidence for the efficacy of FFA treatment modalities specifically in these patients. This systematic review discusses studies on FFA characteristics and treatment outcomes in Black patients.

Telemedicine Alopecia Assessment: Highlighting Patients With Skin of Color.

Alopecia has been one of the more common concerns reported at teledermatology (TD) visits during the COVID-19 pandemic. In light of the growing use of TD, a team of experts were consulted to develop workflows for virtual hair and scalp examinations, with particular consideration for skin of color patients.

An update on cosmetic procedures in people of color. Part 2: Neuromodulators, soft tissue augmentation, chemexfoliating agents, and laser hair reduction.

Recent years have brought forth the undeniable practice gap in dermatology concerning knowledge and experience of cosmetic procedures in people of color (POC). A paucity in the literature regarding evidence-based recommendations for the management of POC undergoing cosmetic procedures and the rise of cosmetic procedures in dermatology serves as a call to action to provide education regarding differences in skin of color that may impact the cosmetic outcomes. To mitigate the current practice gap on the safety, use, and benefits of cosmetic procedures in POC, part 2 will discuss the authors' recommendations and clinical pearls, as well as evidence-based management for neuromodulators, soft tissue augmentation, chemexfoliating agents, and laser hair reduction in POC undergoing cosmetic procedures.

An update on cosmetic procedures in people of color. Part 1: Scientific background, assessment, preprocedure preparation.

Increased life expectancy, focus on appearance, and readily available and accessible cosmetic procedures have served to drive an increase in the number of nonsurgical cosmetic procedures performed in the last 20 years. Demographic shifts in the United States, with increases in diverse populations that seek nonsurgical cosmetic procedures, have resulted in the need for a better understanding of cultural preferences as well as structural and biological differences in the skin of people of color (POC). Although many advances in the form of cosmeceuticals, cosmetics, and photoprotection have been made to address the aesthetic needs of and minimize complications in POC, nonsurgical cosmetic procedures are required to address common aesthetic concerns. Gaps remain in the education of dermatologists regarding the appropriate selection and execution of nonsurgical cosmetic procedures in POC. This educational initiative will facilitate a favorable outcome and optimal cosmetic results for POC.

Psychosocial and psychiatric comorbidities and health-related quality of life in alopecia areata: A systematic review.

BACKGROUND: Alopecia areata (AA) is an immune-mediated disease resulting in nonscarring hair loss. Systematic reviews on the psychosocial and psychiatric comorbidities, health-related quality of life, and interventions targeting psychosocial well-being are limited. OBJECTIVE: To conduct a systematic review of the psychosocial comorbidities, health-related quality of life, and treatment options targeting psychosocial well-being in adult and pediatric AA patients. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines within the PubMed database. Specific search terms included, but were not limited to, alopecia areata, psychosocial, psychiatry, and quality of life. Studies were then evaluated for their design and categorized into corresponding levels of evidence according to the guidelines adapted from the Oxford Center for Evidence Based Medicine. FINDINGS: Seventy-three reports met inclusion criteria, involving approximately 414,319 unique participants. AA patients were found to have psychiatric comorbidities, particularly anxiety and depression. Health-related quality of life is reduced in AA patients, but data on pediatric AA quality of life are limited. Psychotherapy is often recommended as adjuvant treatment. CONCLUSION: AA has substantial psychosocial impact on patients and results in reduced health-related quality of life. Addressing this should be an active part of treatment.

Clinical recognition and management of alopecia in women of color.

Certain types of alopecia, such as traction alopecia, discoid lupus erythematosus, and central centrifugal cicatricial alopecia, occur more commonly in African-American individuals than in those of other ethnicities. Both intrinsic hair qualities and hair care practices play a role. Lower baseline tensile strength, hair density, and growth rates, as well as the use of high-tension hairstyles and chemical relaxers may contribute to alopecia in this group. Alopecia can also occur as a result of discoid lupus erythematosus, which involves chronic lymphocytic infiltration and eventual scarring of the hair follicle. Lichen planopilaris is a less common cause of scarring alopecia that can appear clinically similar to other forms of cicatricial alopecia. Lastly, although not classically associated with hair loss, recent evidence indicates that seborrheic dermatitis may play a role in shedding and alopecia. Recognizing and differentiating these alopecic subtypes clinically and histopathologically is important for prompt diagnosis and treatment. This article is based on a chapter in Ethnic Skin and Hair, and intended as a supplemental article to "Current and Emerging Treatment Strategies for Hair Loss in Women of Color."

Laser Treatments for Postinflammatory Hyperpigmentation: A Systematic Review.

IMPORTANCE: Lasers are gaining interest as a treatment option for postinflammatory hyperpigmentation (PIH) but can pose a clinical dilemma given the risk for laser-induced or exacerbated PIH. OBJECTIVE: To assess the clinical evidence for the use of lasers in the treatment of PIH. EVIDENCE REVIEW: A systematic review was performed by searching PubMed databases from January 1, 1990, through May 31, 2016. Included studies involved laser treatment for PIH with the degree of pigmentation as a measure of outcome. The search was filtered to include only clinical studies written in the English language. Study methods were analyzed and the reproducibility of the studies was graded. Outcome measures varied from study to study and included concentration of melanin and hemoglobin, patient satisfaction questionnaires, clinical photography, subjective clinical improvement, light microscopy, melanin index, reflectance spectroscopy, and/or skin biopsy evaluated by a blinded dermatopathologist. FINDINGS: Of 1295 results, 20 unique studies with 224 patients met the inclusion criteria. These studies included 1 randomized clinical observer-blinded study (6 patients), 4 nonrandomized clinical trials (133 patients), 1 cohort study (34 patients), 7 case series (44 patients), and 7 case reports (7 patients). Multiple lasers were studied; however, most of the studies were not methodologically rigorous. Some studies showed no improvement or worsening of PIH after laser treatment. The most extensively studied device was the Q-switched Nd:YAG laser, which has shown promising results based on multiple outcome measures as listed above. CONCLUSIONS AND RELEVANCE: Some lasers may be beneficial in the treatment of PIH. The evidence suggests that additional studies would be required to determine the benefit of laser treatment of PIH.

Effect of a Pre-Treatment Educational Video in Improving Patient Satisfaction with 5-Fluorouracil Treatment for Actinic Keratoses: A Randomized Controlled Trial.

INTRODUCTION: Patient treatment satisfaction and adherence may be affected by the initial understanding of outcomes in the treatment of actinic keratoses with 5-fluorouracil 5% cream (5-FU). Pre-treatment educational videos may optimize this understanding. The objective of this study was to determine whether prospective patient viewing of an educational video delineating treatment effects and expectations improves patient satisfaction and treatment completion rates for the treatment of actinic keratoses with 5-FU. METHODS: Forty-four participants were recruited to the UC Davis Dermatology outpatient clinic. Each participant was randomized to the video (group A) or control group (group B), and topical 5-FU cream treatment was conducted for 2 weeks in both groups. RESULTS: A follow-up questionnaire was performed to assess patient satisfaction and adherence to the treatment regimen. The results of these questions were analyzed using the Mann-Whitney test. One item on the questionnaire asked the patient to rate their overall level of satisfaction on a score of 0-100. The results of this question were analyzed using the unpaired t test. The results of the statistical analysis show no significant difference between the patient group that viewed the video and the patient group that did not view the video. CONCLUSIONS: We speculate that this study may establish a foundation for subsequent studies that may affect the broader medical community and promote development of educational videos.

Alopecia as the Presenting Symptom of Syphilis.

Alopecia can be one of the many symptoms of secondary syphilis and the clinical presentations include essential syphilitic alopecia or symptomatic syphilitic alopecia. In this report, we present a case of a patient with essential syphilitic alopecia whose sole presenting symptom of syphilis was alopecia. Despite an initial negative rapid plasma reagin (RPR) test, he was ultimately found to have syphilis on scalp biopsy. His alopecia improved following treatment with benzathine penicillin. This presentation serves as a reminder to clinicians to be cognizant of alopecia as a presenting sign of syphilis. A review of the specificity and sensitivity of the typical tests used for the diagnosis is presented.

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.

Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public.

Skin cancer is less prevalent in people of color than in the white population. However, when skin cancer occurs in non-whites, it often presents at a more advanced stage, and thus the prognosis is worse compared with white patients. The increased morbidity and mortality associated with skin cancer in patients of color compared with white patients may be because of the lack of awareness, diagnoses at a more advanced stage, and socioeconomic factors such as access to care barriers. Physician promotion of skin cancer prevention strategies for all patients, regardless of ethnic background and socioeconomic status, can lead to timely diagnosis and treatment. Public education campaigns should be expanded to target communities of color to promote self-skin examination and stress importance of photoprotection, avoidance of tanning bed use, and early skin cancer detection and treatment. These measures should result in reduction or earlier detection of cutaneous malignancies in all communities. Furthermore, promotion of photoprotection practices may reduce other adverse effects of ultraviolet exposure including photoaging and ultraviolet-related disorders of pigmentation.

The use of botanically derived agents for hyperpigmentation: a systematic review.

BACKGROUND: Hyperpigmentation disorders are common among those seeking care from dermatologists and primary care physicians. The cosmeceutical and natural product industries are rapidly growing and many botanical agents are purported to improve hyperpigmentation disorders. OBJECTIVE: We sought to review clinical evidence for the use of botanical agents in the treatment of hyperpigmentation. METHODS: We searched MEDLINE and Embase databases and a total of 26 articles met inclusion criteria. Study methodology was analyzed and the reproducibility of the studies was graded. RESULTS: Several botanical agents appear promising as treatment options but few studies were methodologically rigorous. Several plant extract and phytochemicals effectively lighten signs of epidermal melasma and hyperpigmentation induced by ultraviolet radiation exposure. Results were mixed for treatment of solar lentigines or dermal hyperpigmentation. LIMITATIONS: There were few rigorously designed studies; future research will be critical to further ascertain the discussed results. CONCLUSIONS: The subtype of hyperpigmentation is important for treatment prognosis, with dermal hyperpigmentation less responsive to treatment. Botanical extracts may play an integrative role in the treatment of hyperpigmentation and further studies that integrate them with standard therapies are needed. Side effects, including worsened hyperpigmentation, need to be discussed when considering these therapies.

Quantitative skin color measurements in acanthosis nigricans patients: colorimetry and diffuse reflectance spectroscopy.

Tristimulus colorimetry and diffuse reflectance spectroscopy (DRS) are white-light skin reflectance techniques used to measure the intensity of skin pigmentation. The tristimulus colorimeter is an instrument that measures a perceived color and the DRS instrument measures biological chromophores of the skin, including oxy- and deoxyhemoglobin, melanin and scattering. Data gathered from these tools can be used to understand morphological changes induced in skin chromophores due to conditions of the skin or their treatments. The purpose of this study was to evaluate the use of these two instruments in color measurements of acanthosis nigricans (AN) lesions. Eight patients with hyperinsulinemia and clinically diagnosable AN were seen monthly. Skin pigmentation was measured at three sites: the inner forearm, the medial aspect of the posterior neck, and anterior neck unaffected by AN. Of the three, measured tristimulus L*a*b* color parameters, the luminosity parameter L* was found to most reliably distinguish lesion from normally pigmented skin. The DRS instrument was able to characterize a lesion on the basis of the calculated melanin concentration, though melanin is a weak indicator of skin change and not a reliable measure to be used independently. Calculated oxyhemoglobin and deoxyhemoglobin concentrations were not found to be reliable indicators of AN. Tristimulus colorimetry may provide reliable methods for respectively quantifying and characterizing the objective color change in AN, while DRS may be useful in characterizing changes in skin melanin content associated with this skin condition.

Systemic analyses of immunophenotypes of peripheral T cells in non-segmental vitiligo: implication of defective natural killer T cells.

Although it is widely believed that non-segmental vitiligo (NSV) results from the autoimmune destruction of melanocytes, a clear understanding of defects in immune tolerance, which mediate this uncontrolled self-reactivity, is still lacking. In the present study, we systemically evaluated circulating regulatory T (Treg) cells, including CD4(+) CD25(+) FoxP3(+) Treg cells and invariant natural killer T (iNKT) cells, as well as naïve and memory CD4(+) and CD8(+) T cells and their cytokine production, in a cohort of 43 progressive NSV patients with race-, gender-, and age-matched healthy controls. We found that the general immunophenotypes of CD4(+) and CD8(+) T cells and the percentage of CD4(+) CD25(+) FoxP3(+) Tregs were comparable between NSV and healthy controls. However, percentages of peripheral iNKT cells were significantly decreased in NSV patients compared to that in healthy controls. Our data confirm the previous notion that the percentage of peripheral CD4(+) CD25(+) FoxP3(+) Tregs remains unaltered in NSV and suggests the involvement of defective iNKT cells in the pathogenesis of NSV.

The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells.

The endogenous purine nucleoside adenosine is an important antiinflammatory mediator that contributes to the control of CD4(+) T cell responses. While adenosine clearly has direct effects on CD4(+) T cells, it remains to be determined whether actions on APC such as dendritic cells (DC) are also important. In this report we characterize DC maturation and function in BMDC stimulated with LPS in the presence or absence of the nonselective adenosine receptor agonist NECA (5'-N-ethylcarboxamidoadenosine). We found that NECA inhibited TNF-alpha and IL-12 in a concentration-dependent manner, whereas IL-10 production was increased. NECA-treated BMDC also expressed reduced levels of MHC class II and CD86 and were less effective at stimulating CD4(+) T cell proliferation and IL-2 production compared with BMDC exposed to vehicle control. Based on real-time RT-PCR, the A(2A) adenosine receptor (A(2A)AR) and A(2B)AR were the predominant adenosine receptors expressed in BMDC. Using adenosine receptor subtype selective antagonists and BMDC derived from A(2A)AR(-/-) and A(2B)AR(-/-)mice, it was shown that NECA modulates TNF-alpha, IL-12, IL-10, and CD86 responses predominantly via A(2B)AR. These data indicate that engagement of A(2B)AR modifies murine BMDC maturation and suggest that adenosine regulates CD4(+) T cell responses by selecting for DC with impaired immunogencity.