scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in Treg function.

Vitiligo is an autoimmune skin disease characterized by the targeted destruction of melanocytes by T cells. Cytokine signaling between keratinocytes and T cells results in CD8+ T cell infiltration of vitiligo lesions, but the full scope of signals required to coordinate autoimmune responses is not completely understood. We performed single-cell RNA sequencing on affected and unaffected skin from patients with vitiligo, as well as healthy controls, to define the role of each cell type in coordinating autoimmunity during disease progression. We confirmed that type 1 cytokine signaling occupied a central role in disease, but we also found that this pathway was used by regulatory T cells (Tregs) to restrain disease progression in nonlesional skin. We determined that CCL5-CCR5 signaling served as a chemokine circuit between effector CD8+ T cells and Tregs, and mechanistic studies in a mouse model of vitiligo revealed that CCR5 expression on Tregs was required to suppress disease in vivo but not in vitro. CCR5 was not required for Treg recruitment to skin but appeared to facilitate Treg function by properly positioning these cells within the skin. Our data provide critical insights into the pathogenesis of vitiligo and uncover potential opportunities for therapeutic interventions.

Bitemporal Scalp Hair Loss: Differential Diagnosis of Nonscarring and Scarring Conditions.

BACKGROUND: Bitemporal hair loss can be a diagnostic challenge because several entities may affect this region of the scalp, including both scarring and nonscarring conditions. Although traction alopecia is the most common cause of bitemporal hair loss, no studies to date have outlined all of the potential causes. OBJECTIVE: We sought to review nonscarring and scarring conditions that have a clinical presentation of bitemporal hair loss, including traction alopecia, telogen effluvium, female pattern hair loss, frontal fibrosing alopecia, central centrifugal cicatricial alopecia, and seborrheic dermatitis. METHODS: A Google Scholar and PubMed literature search were conducted for this review. The keywords used in the search included the following: "traction alopecia", "telogen effluvium", "androgenic alopecia", "androgenetic alopecia", "female pattern hair loss", "alopecia areata", "frontal fibrosing alopecia", "central centrifugal cicatricial alopecia", and "seborrheic dermatitis". The scope of our search included all research articles published from 1957 to February 2019. In total, 94 articles regarding non-scarring and scarring hair loss were selected and included according to topic relevance. Exclusion criteria included articles that did not address the epidemiology and/or clinicopathologic or dermatoscopic findings of non-scarring and scarring forms of alopecia. Inclusion criteria included articles that addressed a clinical presentation of bitemporal hair loss; or addressed epidemiology, clinical presentation, dermatoscopic findings, and/or treatment. RESULTS: Bitemporal hair loss is a common and often distressing condition with a broad differential. CONCLUSION: Clinicians must be aware of the potential causes of bitemporal hair loss. Prompt diagnosis is essential to prevent further hair loss, especially in scarring conditions.

Biallelic variants in RNU12 cause CDAGS syndrome.

CDAGS Syndrome is a rare congenital disorder characterized by Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations. We performed whole exome and Sanger sequencing to identify the underlying molecular cause in five patients with CDAGS syndrome from four distinct families. Whole exome sequencing revealed biallelic rare variants that disrupt highly conserved nucleotides within the RNU12 gene. RNU12 encodes a small nuclear RNA that is a component of the minor spliceosome and is essential for minor intron splicing. Targeted sequencing confirmed allele segregation within the four families. All five patients shared the same rare mutation NC_000022.10:g.43011402C>T, which alters a highly conserved nucleotide within the precursor U12 snRNA 3' extension. Each of them also carried a rare variant on the other allele that either disrupts the secondary structure or the Sm binding site of the RNU12 snRNA. Whole transcriptome sequencing analysis of lymphoblastoid cells identified 120 differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events in the patient. These findings provide evidence of the involvement of RNU12 in craniosynostosis, anal and genitourinary patterning, and cutaneous disease.

Intralesional Triamcinolone Acetonide in the Treatment of Traction Alopecia

Traction alopecia (TA) is a form of hair loss caused by continuous and prolonged tension to the hair, most commonly seen in Black/African American women and children who wear hairstyles that pull excessively at the frontotemporal hairline. Dermatologists have recommended the use of intralesional triamcinolone acetonide injections (ILK) to decrease the inflammatory process, however, evidence-based proof is lacking in the literature. In this case series, we evaluate the effectiveness and safety of ILK in the TA management of 6 African American women. A retrospective chart review was done of patients with a diagnosis of TA, who were treated with ILK at an academic dermatology clinic, yielding 6 patients. Management of TA was assessed by comparing the photographs for changes in hair density along the frontotemporal hairline. ILK with a concentration of 5 mg/mL, was administered in areas of low hair density along the frontotemporal hairline at 6 to 8-week intervals, for 3 successive visits. All subjects demonstrated visible increase in hair density along the frontotemporal hairline following their first or second treatment, and no severe adverse effects were observed or reported. The use of ILK is currently an effective and safe method of treating TA, particularly in the early to mid-stages. Common adverse effects are pain, and subsequent transient atrophy at the injection site. The transient atrophy is not an indication to stop treatment. Avoidance of treating dented areas is sufficient to allow it to revert. Patient education is pivotal in the prevention and management of TA. It is imperative that dermatologists caution against grooming practices that exert tension on the hairline. J Drugs Dermatol. 2020;19(2)128-130. doi:10.36849/JDD.2020.4635

Randomised, controlled, double-blind study of combination therapy of oral tranexamic acid and topical hydroquinone in the treatment of melasma.

BACKGROUND/OBJECTIVES: Melasma is a common pigmentary disorder for which oral tranexamic acid has shown some efficacy in previous studies. The aim of this study was to assess the effectiveness of oral tranexamic acid in combination with hydroquinone cream in the treatment of melasma. METHODS: Subjects with moderate-to-severe melasma were enrolled. Group A received hydroquinone 4% cream, sunscreen and oral tranexamic acid, while Group B received hydroquinone 4% cream, sunscreen and placebo capsules for 3 months. All subjects had an additional 3-month follow-up visit on sunscreen alone. The primary outcome measure was change in modified Melasma Area and Severity Index (mMASI) score. In addition, the melanin index was measured using a mexameter. RESULTS: Fifty subjects were enrolled, and all completed the study. There was a 55% reduction in mMASI after 3 months from mean 8.96 (SD 2.45) to 4.0 (SD 1.6) in Group A compared to 10.9% from mean 8.53 (SD 2.04) to 7.6 (SD 2.0) in Group B. Three months after oral and topical therapy was discontinued, there was a 42% decrease in mMASI compared to baseline in Group A (mean 5.1 SD 1.7) vs. 4.7% in Group B (mean 8.1 SD 2.0). No serious adverse events were observed. CONCLUSIONS: A combination of oral tranexamic acid and topical hydroquinone is more effective than hydroquinone alone in the treatment of melasma.

Melasma Treatment: An Evidence-Based Review.

BACKGROUND: Melasma is an acquired, chronic pigmentary disorder predominantly affecting women. It may significantly affect quality of life and self-esteem due to its disfiguring appearance. Multiple treatments for melasma are available, with mixed results. OBJECTIVE: The aim of this article was to conduct an evidence-based review of all available interventions for melasma. METHODS: A systematic literature search of the PubMed electronic database was performed using the keywords 'melasma' and/or 'chloasma' in the title, through October 2018. The search was then limited to 'randomized controlled trial' and 'controlled clinical trial' in English-language journals. The Cochrane database was also searched for systematic reviews. RESULTS: The electronic search yielded a total of 212 citations. Overall, 113 studies met the inclusion criteria and were included in this review, with a total of 6897 participants. Interventions included topical agents, chemical peels, laser- and light-based devices, and oral agents. Triple combination cream (hydroquinone, tretinoin, and corticosteroid) remains the most effective treatment for melasma, as well as hydroquinone alone. Chemical peels and laser- and light-based devices have mixed results. Oral tranexamic acid is a promising new treatment for moderate and severe recurrent melasma. Adverse events from all treatments tend to be mild, and mainly consist of skin irritation, dryness, burning, erythema, and post-inflammatory hyperpigmentation. CONCLUSIONS: Hydroquinone monotherapy and triple combination cream are the most effective and well-studied treatments for melasma, whereas chemical peels and laser- and light-based therapies are equal or inferior to topicals, but offer a higher risk of adverse effects. Oral tranexamic acid may be a safe, systemic adjunctive treatment for melasma, but more studies are needed to determine its long-term safety and efficacy. Limitations of the current evidence are heterogeneity of study design, small sample size, and lack of long-term follow-up, highlighting the need for larger, more rigorous studies in the treatment of this recalcitrant disorder.

Cross-cultural validation of a short-form of the Vitiligo Impact Patient scale (VIPs).

BACKGROUND: There is a lack of short-form questionnaires evaluating the burden of vitiligo according to skin phototype. OBJECTIVE: To develop and validate a 12-item short-form of the Vitiligo Impact Patient scale (VIPs) that takes into account skin phototype. METHODS: Multicenter, prospective, cross-sectional study conducted in France (Créteil and Bordeaux) and the US (Worcester, Massachusetts, and Dallas, Texas). RESULTS: In total, 891 patients completed the questionnaire. Of these, 509 patients belonged to the French Development sample-313 with dark skin (DS) (phototypes IV to VI) and 196 with fair skin (FS) (phototypes I to III). The US validation sample comprised 382 patients-113 DS and 269 FS. There was a very high correlation between VIPs-FS and its 12-item short-form, VIPs-12-FS, in both the development and validation samples (respectively, rho = 0.96, P < .0001 and rho = 0.98, P < .0001). Similarly, the correlations between VIPs-DS and its short-form, VIPs-12-DS, in both the development and validation samples were very high (respectively, rho = 0.95, P < .0001 and rho = 0.96, P < .0001). LIMITATIONS: Responsiveness of the 12-item short-forms should be confirmed. CONCLUSIONS: These data enabled the development and validation of 12-item short-forms of the VIPs questionnaires for fair (VIPs-12-FS) and dark (VIPs-12-DS) skin.

Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo.

Vitiligo is an autoimmune disease of the skin mediated by CD8+ T cells that kill melanocytes and create white spots. Skin lesions in vitiligo frequently return after discontinuing conventional treatments, supporting the hypothesis that autoimmune memory is formed at these locations. We found that lesional T cells in mice and humans with vitiligo display a resident memory (TRM) phenotype, similar to those that provide rapid, localized protection against reinfection from skin and mucosal-tropic viruses. Interleukin-15 (IL-15)-deficient mice reportedly have impaired TRM formation, and IL-15 promotes TRM function ex vivo. We found that both human and mouse TRM express the CD122 subunit of the IL-15 receptor and that keratinocytes up-regulate CD215, the subunit required to display the cytokine on their surface to promote activation of T cells. Targeting IL-15 signaling with an anti-CD122 antibody reverses disease in mice with established vitiligo. Short-term treatment with anti-CD122 inhibits TRM production of interferon-γ (IFNγ), and long-term treatment depletes TRM from skin lesions. Short-term treatment with anti-CD122 can provide durable repigmentation when administered either systemically or locally in the skin. On the basis of these data, we propose that targeting CD122 may be a highly effective and even durable treatment strategy for vitiligo and other tissue-specific autoimmune diseases involving TRM.

Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma.

BACKGROUND: Melasma is a common pigmentary disorder that is often difficult to treat. Tranexamic acid (TA) has emerged as a promising treatment for melasma; however, few controlled studies exist. OBJECTIVE: To determine the efficacy of oral TA in patients with moderate-to-severe melasma. METHODS: Patients with moderate-to-severe melasma were treated with 250 mg of TA or placebo capsules twice daily for 3 months and sunscreen followed by 3 months of treatment with sunscreen only. The primary outcome measure was the modified Melasma Area and Severity Index (mMASI) score. RESULTS: A total of 44 patients were enrolled and 39 completed the study. At 3 months, there was a 49% reduction in mMASI score in the TA group versus 18% in the control group. Patients with severe melasma improved more than those with moderate melasma. Three months after treatment was stopped, there was a 26% reduction in mMASI score in the TA group compared with the baseline visit versus a 19% reduction in the placebo arm. No serious adverse events were noted in either group. LIMITATIONS: Single-center study enrolling predominantly Hispanic women. CONCLUSIONS: Oral TA appears to be an effective treatment for moderate-to-severe melasma with minimal side effects.

Psoriasis in Children and Adolescents: Epidemiological Study of 280 Patients from Mexico.

BACKGROUND: Psoriasis in children and adolescents has not been well studied in Mexico. OBJECTIVE: To study the epidemiological characteristics of psoriasis in this age group. METHODS: This is a retrospective study in an academic, tertiary care dermatology center from January 1999 to December 2014. We included patients ≤ 18 years of age, with clinical and histopathological diagnosis of psoriasis. We recorded the following information: gender, age, disease duration, clinical variant, nail involvement, treatment, and family history. Descriptive and inferential statistics were used for analysis. RESULTS: Of 2,491 patients with psoriasis, 280 were ≤ 18 years of age, resulting in a prevalence of 11%. There was female predominance and the mean age was 11.5 years. Disease duration was 18 ± 34 months. Plaque psoriasis was the most common form, comprising 191 cases (68%). Nail involvement occurred in only 15 patients (5%). Topical treatment was given to 177 patients (63%). Only 14 cases (5%) had a family history of psoriasis. These variables did not differ when children were compared with adolescents, except in those with a shorter disease duration (13 ± 19 vs. 24 ± 29 months; p = 0.0004). CONCLUSIONS: We found a higher prevalence of psoriasis than previously published studies in this age group and a lower frequency of nail involvement and family history of psoriasis.