Proteomic Profiling of Central Centrifugal Cicatricial Alopecia Reveals Role of Humoral Immune Response Pathway and Metabolic Dysregulation.

Proteomic profiling on other primary cicatricial alopecias, such as frontal fibrosing alopecia and lichen planopilaris, have suggested a T helper 1-mediated inflammatory pathway, but in central centrifugal cicatricial alopecia (CCCA), the protein expression patterns are unknown. In this study, we sought to characterize protein expression patterns in CCCA to identify biomarkers of disease activity that will identify potential therapeutic avenues for treatment. Scalp protein quantification was performed to understand protein expression patterns in affected versus unaffected scalps in CCCA. A total of 5444 proteins were identified, of which 148 proteins were found to be differentially expressed in CCCA-affected scalp, with upregulation of adaptive immune pathways (IGHG3, P = .034; IGHG4, P = .01; IGG1, P = .026) and markers of fibrosis (ITGA1, P = .016; SFRP2, P = .045; TPM2, P = .029; SLMAP, P = .016) and downregulation of metabolic proteins (ALOX15B, P = .003; FADS2, P = .006; ELOVL5, P = .007; FA2H, P = .017; FAR2, P = .011; SC5D, P < .001). Our analysis revealed, to our knowledge, previously unknown humoral immune canonical pathways, notably IgG, implicated in CCCA and additionally confirmed aberrant lipid metabolism pathways implicated in diabetes mellitus, suggesting unique mechanisms of disease in patients with CCCA.

Updates on disorders in curly hair.

Hair disorders, including central centrifugal cicatricial alopecia (CCCA), traction alopecia (TA), and acquired trichorrhexis nodosa (ATN), commonly occur in individuals with curly textured hair. Curly textured hair in individuals of African descent has unique properties and can present diagnostic and therapeutic challenges. CCCA has been linked to uterine leiomyoma and type 2 diabetes mellitus, as well as fibroproliferation. TA often presents with a fringe sign and can arise from high-tension hairstyles presumed to be protective. Trichoscopy is useful in establishing a diagnosis; perifollicular halos are more commonly seen than perifollicular erythema or scale in CCCA. In TA, miniaturized follicles, hair casts, and "flambeau sign" can be seen. Hairstyling practices likely contribute to TA and ATN; however, the data are mixed on the role of chemical relaxers and heat styling in CCCA. Unique considerations in the presentation of frontal fibrosing alopecia in curly textured hair have also been published recently. This review provides a comprehensive, up-to-date summary of these disorders with an emphasis on their unique properties, as well as considerations in hair care for curly textured hair.

Treatment for central centrifugal cicatricial alopecia-Delphi consensus recommendations.

BACKGROUND: There is no established standard of care for treating central centrifugal cicatricial alopecia (CCCA), and treatment approaches vary widely. OBJECTIVE: To develop consensus statements regarding the use of various pharmacological therapies in treating adults with CCCA. METHODS: We invited 27 dermatologists with expertise in hair and scalp disorders to participate in a 3-round modified Delphi study between January and March 2023. Statements met strong consensus if 75% of respondents agreed or disagreed. Statements met moderate consensus if 55% or more but less than 75% agreed or disagreed. RESULTS: In round 1, 5 of 33 (15.2%) statements met strong consensus, followed by 9 of 28 (32.1%) in round 2. After the final round 3 meeting, strong consensus was reached for 20 of 70 (28.6%) overall statements. Two statements achieved moderate consensus. LIMITATIONS: This study included only English-speaking, US-based dermatologists and did not consider nonpharmacological therapies. CONCLUSION: Despite varying opinions among dermatologists, consensus was reached for several statements to help clinicians manage CCCA. We also highlight areas that lack expert consensus with the goal of advancing research and therapeutic options for CCCA.

ERK hyperactivation serves as a unified mechanism of escape in intrinsic and acquired CDK4/6 inhibitor resistance in acral lentiginous melanoma.

Patients with metastatic acral lentiginous melanoma (ALM) suffer worse outcomes relative to patients with other forms of cutaneous melanoma (CM), and do not benefit as well to approved melanoma therapies. Identification of cyclin-dependent kinase 4 and 6 (CDK4/6) pathway gene alterations in >60% of ALMs has led to clinical trials of the CDK4/6 inhibitor (CDK4i/6i) palbociclib for ALM; however, median progression free survival with CDK4i/6i treatment was only 2.2 months, suggesting existence of resistance mechanisms. Therapy resistance in ALM remains poorly understood; here we report hyperactivation of MAPK signaling and elevated cyclin D1 expression serve as a mechanism of intrinsic early/adaptive CDK4i/6i resistance. ALM cells that have acquired CDK4i/6i resistance following chronic treatment exposure also exhibit hyperactivation of the MAPK pathway. MEK and/or ERK inhibition increases CDK4i/6i efficacy against therapy naïve and CDK4i/6i-resistant AM cells in xenograft and patient-derived xenograft (PDX) models and promotes a defective DNA repair, cell cycle arrested and apoptotic program. Notably, gene alterations poorly correlate with protein expression of cell cycle proteins in ALM or efficacy of CDK4i/6i, urging additional strategies when stratifying patients for CDK4i/6i trial inclusion. Concurrent targeting of the MAPK pathway and CDK4/6 represents a new approach for patients with metastatic ALM to improve outcomes.

Considerations and recommendations on camouflage in alopecia in Black women.

Alopecia is among the leading dermatological concerns affecting Black women. For many women, hair is a central component of identity and self-expression, the loss of which can have significant psychosocial effects. Hair camouflage is often utilized to minimize the visibility of hair loss, provide aesthetic benefits, and improve quality of life. The versatility and affordability of hair camouflage allows patients with alopecia to conceal hair loss, increasing self-confidence, and decreasing social stigma. However, hair camouflage practices often involve adhesives, chemicals, and/or high-tension braiding, all of which can exacerbate alopecia. Accordingly, special considerations should be made to protect patients' natural hair from damage while using these styling practices. A better understanding of best practices for some of the most widely used camouflage options-wigs, extensions, topical hair fibers, and micropigmentation-can help clinicians establish rapport with Black women and optimize individually-tailored therapeutic plans during active treatment and end-stage hair loss.

Presence of Uterine Leiomyomas Has No Significant Impact on Gene Expression Profile in the Scalp of Patients with Central Centrifugal Cicatricial Alopecia.

Central centrifugal cicatricial alopecia (CCCA) is associated with increased expression of genes implicated in fibroproliferative disorders and a higher prevalence of uterine leiomyomas (ULs) among affected individuals. We sought to examine the effect of UL status on the gene expression profile of the lesional scalp in patients with CCCA. Scalp biopsy was obtained from 16 patients with a confirmed diagnosis of CCCA between 2017 and 2020. Microarray analysis was used to identify differential gene expression between patients with CCCA with a history of UL and those without the history. Of more than 20,000 genes analyzed, 23 of 25 genes with the highest expression in patients with CCCA with UL held no statistical significance. No genes previously implicated in fibroproliferative disorders were found among the upregulated transcripts. Of all genes analyzed, only eight upregulated genes and zero downregulated genes had a fold change in expression >2 in patients with CCCA with UL compared with those in patients with CCCA without UL. Our findings highlight similar gene expression patterns in the lesional scalp of patients with CCCA with and without a history of UL. This analysis is key in highlighting no evidence of causational or linked mechanobiology that accounts for the increased prevalence of UL seen in patients with CCCA that previous studies have not addressed.

Gene expression profiling suggests severe, extensive central centrifugal cicatricial alopecia may be both clinically and biologically distinct from limited disease subtypes.

The natural history of central centrifugal cicatricial alopecia (CCCA) is widely variable. Some patients experience rapid progression to extensive, end-stage disease while others never approach extensive involvement over decades, suggesting heterogeneity in CCCA disease phenotype. To better characterize clinically severe disease in CCCA, tissue samples were obtained from the peripheral, hair-bearing lesional scalp of women with clinically focal, limited and extensive CCCA disease involvement. A microarray analysis was conducted to identify differential expression of genes previously identified to be preferentially expressed in the lesional scalp vs. non-lesional scalp of CCCA patients. Clinically extensive, severe CCCA was characterized by increased expression of MMP9, SFRP4 and MSR1 when directly compared with focal and limited disease. These biomarkers correspond to dysregulated pathways of fibrosis, Wnt signalling and macrophage-mediated inflammatory processes respectively. These findings hold significance for both possible targets for future study of prognostic markers of disease severity and new potential therapeutic targets. In summary, this study suggests clinically extensive, severe CCCA may have a differential gene expression pattern in the lesional scalp of affected patients, in addition to its clinical distinction.

Development of the alopecia areata scale for clinical use: Results of an academic-industry collaborative effort.

BACKGROUND: The current classification for alopecia areata (AA) does not provide a consistent assessment of disease severity. OBJECTIVE: To develop an AA severity scale based on expert experience. METHODS: A modified Delphi process was utilized. An advisory group of 22 AA clinical experts from the United States was formed to develop this AA scale. Representatives from the pharmaceutical industry provided feedback during its development. RESULTS: Survey responses were used to draft severity criteria, aspiring to develop a simple scale that may be easily applied in clinical practice. A consensus vote was held to determine the final AA severity statement, with all AA experts agreeing to adopt the proposed scale. LIMITATIONS: The scale is a static assessment intended to be used in clinical practice and not clinical trials. CONCLUSION: The final AA disease severity scale, anchored in the extent of hair loss, captures key features commonly used by AA experts in clinical practice. This scale will better aid clinicians in appropriately assessing severity in patients with this common disease.

Genetic characteristics and response to systemic therapies of acral lentiginous melanoma at a tertiary care center-a retrospective review.

BACKGROUND: Acral lentiginous melanoma (ALM) is an aggressive subtype of cutaneous malignant melanomas that accounts for 50-80% of melanomas in ethnic minorities. Studies on the genetic profile of these tumors largely result from cohorts in Europe, Asia, and Latin America, few inclusive of Black patients. OBJECTIVE: We aim to describe the clinicopathological and genetic characteristics in a diverse cohort of ALM patients. METHODS: A retrospective analysis of 93 patients with a pathology confirmed diagnosis of ALM between March 1984 and October 2020 was conducted at a large tertiary care center. Melanoma mutation panel testing for frequently mutated regions of the BRAF, NRAS, KIT and PIK3CA genes were reviewed in patient records when available. RESULTS: Of the 93 patients identified, 62.4% were Caucasian, 25.8% Black, 4.30% Hispanic, 4.30% Asian, and 3.22% identified as other. Fourteen of 17 patients receiving targeted or immunologic agents experienced disease progression during treatment, including all patients with a BRAF V600E mutation. LIMITATIONS: This was a single-center retrospective analysis. CONCLUSION: Response to targeted and immunologic therapies in ALM patients was overwhelming poor, particularly in BRAF V600E-mutated tumors in contrast to the positive prognosis associated with BRAF V600E mutations in other advanced cutaneous melanoma subtypes.

An Approach to Patients with Alopecia.

Alopecia is a dermatologic condition in which sudden or gradual loss of hair occurs on 1 or more areas of the body, most commonly the scalp. Hair loss can be acute or chronic in nature as a result of underlying inflammation, autoimmune processes, stressors, chemotherapy, or hairstyling practices. Alopecia can have substantial psychological consequences, having a negative impact on the quality of life in affected patients. The ability to both recognize and distinguish these condition holds great significance not only in providing adequate and timely treatment to improve outcomes but also meeting patient needs.

Approach to treatment of refractory dissecting cellulitis of the scalp: a systematic review.

BACKGROUND: Dissecting cellulitis is a chronic inflammatory dermatosis that results in disfiguring and painful, purulent lesions. Treatment of patients with disease resistant to standard therapies, including intralesional or topical steroids or antibiotics, can be a dilemma for clinicians. METHODS: We performed a systematic review of the literature in November 2018 to find articles which presented treatment options and outcomes of patients who failed prior treatment with standard therapies. RESULTS: We identified 57 articles of interest, with 53 being case studies or series. Isotretinoin was the most often reported, but the response was limited. Biologics and laser therapy were used less often but demonstrated a better chance of remission. X-ray epilation and surgical excision demonstrated the best remission rates but can be complicated by serious morbidity. CONCLUSION: We propose a regimen for the treatment of recalcitrant cases of dissecting cellulitis. In the future, more robust studies including randomized control trials are needed to identify the preferred treatment options for refractory dissecting cellulitis.