Alopecia areata is a medical disease

Korta, Dorota Z.; Christiano, Angela M.; Bergfeld, Wilma F.; Duvic, Madeleine; Ellison, Abby; Fu, Jennifer; Harris, John E.; Hordinsky, Maria; King, Brett; Kranz, Dory; Mackay‐Wiggan, Julian; McMichael, Amy J.; Norris, David A.; Price, Vera H.; Shapiro, Jerry; Mesinkovska, Natasha Atanaskova

doi:10.1016/j.jaad.2017.09.011

Cited by 40 publications

(39 citation statements)

References 31 publications

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“…Alopecia is a prevalent problem that not only affects psychological well‐being, but also endangers certain inherent functions of the skin. However, currently available treatments, including drug therapies and human hair transplantation, have numerous limitations . Discovery of Norrin function in dermal papilla physiology could bring novel therapeutic tools.…”

Section: Resultsmentioning

confidence: 99%

Extracellular Vesicles from Activated Dermal Fibroblasts Stimulate Hair Follicle Growth Through Dermal Papilla-Secreted Norrin

Riche

Aberdam

Marchand³

et al. 2019

Stem Cells

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Dermal papilla cells (DPCs) play a pivotal role in the regulation of hair follicle (HF) growth, formation, and cycling, mainly through paracrine mechanisms. In the last decade, extracellular vesicles (EVs) have been recognized as a new paracrine mechanism that can modify the physiological state of recipient cells by transferring biological material. Herein, we investigated the effect of EVs isolated from stimulated human dermal fibroblasts (DFs) on DPC activation and HF growth. We found that these EVs (st-EVs) enhanced HF growth ex vivo. Comparative transcriptomic analysis on DPCs identified specific activation of the NDP gene, encoding the non-Wnt ligand Norrin. We found that Norrin was secreted by st-EVs-stimulated DPCs activating in a noncell autonomous manner β-catenin pathway in follicular keratinocytes (human HF keratinocyte [HHFK]) and hair growth ex vivo. Although Norrin-specific receptor Frizzled4 was barely detected in HHFK, we found its presence in DF-EVs. Accordingly, DF-EVs provided Frizzled4 to potentiate Norrin effects ex vivo. Our study identifies DF-EVs as efficient activators of DPCs and Norrin as a novel modulatory player in HF physiopathology. STEM CELLS 2019;37:1166-1175 SIGNIFICANCE STATEMENTDermal papilla cells (DPCs) control the growth and regeneration of hair follicles (HFs) via cellcell interactions and extracellular molecules. These data demonstrate that activated dermal fibroblasts (DFs) secrete specific extracellular vesicles (st-EVs) that enhance HF growth ex vivo. DPCs treated with st-EVs secrete Norrin, a non-Wnt ligand that activates the β-catenin pathway of recipient human hair follicular keratinocytes. DF-EVs contain Norrin-specific Frizzled4 receptor that is barely detected in human HF keratinocytes. Combinatory treatment of Norrin and DF-EVs is sufficient to recapitulate the stimulating effect ex vivo of st-EVs on HF growth. The study identifies Norrin as a novel modulatory player in HF physiopathology.

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Section: Resultsmentioning

confidence: 99%

Extracellular Vesicles from Activated Dermal Fibroblasts Stimulate Hair Follicle Growth Through Dermal Papilla-Secreted Norrin

Riche

Aberdam

Marchand³

et al. 2019

Stem Cells

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“…Few qualitative studies have conceptualized the relationship between AA signs/symptoms and the psychosocial burden of this medical disease [ 24 ], and while conceptual frameworks of the physical and psychosocial burden of skin disease have been hypothesized by Chren in the development of the Skindex [ 25 , 26 ], no conceptual model to represent the particular effects of AA has been developed to inform patient-reported outcome (PRO) measurement.…”

Section: Introductionmentioning

confidence: 99%

“‘You lose your hair, what’s the big deal?’ I was so embarrassed, I was so self-conscious, I was so depressed:” a qualitative interview study to understand the psychosocial burden of alopecia areata

Aldhouse¹,

Kitchen²,

Knight³

et al. 2020

J Patient Rep Outcomes

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Background Alopecia areata (AA) is characterized by hair loss that can affect the scalp and body. This study describes the psychosocial burden of AA. Methods Participants diagnosed with AA who had experienced ≥50% scalp hair loss according to the Severity of Alopecia Tool (SALT) were identified by clinicians. A semi-structured interview guide, developed with expert clinician input, included open-ended questions to explore patients’ experiences of living with AA. Data were thematically analyzed to identify concepts and relationships. Results Participants (n = 45, 58% female, mean age 33.3 years [range 15–72], mean SALT 67.2 [range 0–100]) described the AA diagnosis as “devastating”. Both males and females reported emotional and psychological impacts of AA including feeling sad/depressed (n = 21), embarrassed/ashamed (n = 10) and angry/frustrated (n = 3). Patients felt helpless (n = 5) due to the unpredictability of disease recurrence, and anxious (n = 19) about judgement from others. Many patients avoided social situations (n = 18), which impaired relationships and increased isolation. Coping strategies included concealment of hair loss through wigs or make-up, although fear of the displacement of these coverings also caused anxiety and the avoidance of activities that could result in scalp exposure (n = 22). Some patients became more accepting of AA over time, which lessened the emotional impact, though efficacious treatment was still desired. A conceptual framework was developed, and a conceptual model was created to depict the relationship between the physical signs/symptoms and the associated psychosocial effects of AA. Conclusion AA impairs patients’ emotional and psychological wellbeing, relationships and lifestyles. Greater disease awareness and effective treatments are needed.

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“…Alopecia areata (AA) is a patchy chronic autoimmune-mediated disease that targets the anagen hair follicles and causes non-scarring alopecia. 1 Although there are not Food and Drug Administration (FDA) approval treatments, corticosteroids are considered first-line therapy. 2 Besides, the available treatments do not induce a complete and permanent cure.…”

Section: Introductionmentioning

confidence: 99%