Lichen Planopilaris and Frontal Fibrosing Alopecia as Model Epithelial Stem Cell Diseases

Harries, Matthew; Jiménez, Francisco; Izeta, Ander; Hardman, Jonathan A.; Panicker, Sreejith Parameswara; Poblet, Enrique; Paus, Ralf

doi:10.1016/j.molmed.2018.03.007

Cited by 91 publications

(152 citation statements)

References 97 publications

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“…A collapse of the immune privilege is a key element in the pathogenesis of chronic scalp diseases. The question as to whether the bulb or the bulge immune privilege is disturbed determines if the hair follicle itself is preserved of long time periods, as observed in AA, or if a hair follicle is permanently lost as observed in cicatricial alopecia …”

Section: Scalp Hair Follicle As a Distinct And Complex Organmentioning

confidence: 99%

“…The latter is probably observed in acne vulgaris and hidradenitis suppurativa, but the exact mechanisms underlying the microbial contribution to the disease and targeted effective treatment remain to be determined . Moreover, disturbance of immune‐privileged sites and autoimmune reactions are key events in chronic hair follicle diseases such as alopecia areata (AA) and lichen planopilaris, in which immunosuppressive and immunomodulatory agents are widely used but not always with satisfactory results …”

Section: Introductionmentioning

confidence: 99%

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The role of the microbiome in scalp hair follicle biology and disease

Polak-Witka

Rudnicka

Blume-Peytavi

et al. 2019

Experimental Dermatology

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The skin surface microbiome and its role in skin diseases have received increasing attention over the past years. Beyond, there is evidence for a continuous exchange with the cutaneous immune system in healthy skin, where hair follicles (HFs) provide unique anatomical niches. Especially, scalp HFs form large tubular invaginations, which extend deeply into the skin and harbour a variety of microorganisms. The distinct immunology of HFs with enhanced immune cell trafficking in superficial compartments in juxtaposition to immune‐privileged sites crucial for hair follicle cycling and regeneration makes this organ a highly susceptible structure. Depending on composition and penetration depth, microbiota may cause typical infections, but may also contribute to pro‐inflammatory environment in chronic inflammatory scalp diseases. Involvement in hair cycle regulation and immune cell maturation has been postulated. Herein, we review recent insights in hair follicle microbiome, immunology and penetration research and discuss clinical implications for scalp health and disease.

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Section: Scalp Hair Follicle As a Distinct And Complex Organmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of the microbiome in scalp hair follicle biology and disease

Polak-Witka

Rudnicka

Blume-Peytavi

et al. 2019

Experimental Dermatology

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“…These infiltrates are dominated by activated MACs that accumulate around the stem cell region of 10% of late anagen and catagen HFs in healthy mouse skin leading to immune ablation of isolated HFs . It has been speculated that this could be a controlled physiological mechanism to remove ageing or malfunctioning HFs, which may become excessive in lymphocytic scarring alopecia's such as lichen planopilaris and frontal fibrosing alopecia . It is important to clarify that the pfMAC activities investigated above are likely to represent several phenotypic MACs subtypes, as tissue‐resident MAC populations are commonly heterogenous and it could be considered reductionist to view all MACs as responsible …”

Section: Perifollicular Macrophages: Basicsmentioning

confidence: 99%

“…Other important open questions are how MAC‐dependent “programmed organ deletion” of selected, isolated HFs is regulated (eg by the release of MAC‐targeting cytokines and chemokines or by damaged/malfunctioning HF keratinocytes?) and to what extent this phenomenon occurs not just in murine but also human skin, namely in primary scarring alopecias …”

Section: Major Open Questionsmentioning

confidence: 99%

“…Exploring the role of pfMACs in establishing the immune privilege that transiently exists in the anagen hair bulb and permanently in the bulge region of the HF may also be productive, considering that tissue‐resident MACs in other organ systems are responsible for local immune privilege . Since its disruption is critically involved in the pathophysiology of inflammatory hair loss disorders like alopecia areata and lichen planopilaris, it is important to clarify what role pfMACs may play in HF immune privilege collapse.…”

Section: Major Open Questionsmentioning

confidence: 99%

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Hair growth control by innate immunocytes: Perifollicular macrophages revisited

Muneeb

Hardman

Paus

2019

Experimental Dermatology

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The role of innate immunocytes such as mast cells, γδ T cells, NK cells and macrophages (MACs) in hair growth control under physiological and pathological conditions has recently begun to be re‐explored. Here, we revisit the role of resident perifollicular macrophages (pfMACs) located in the hair follicle (HF) mesenchyme (CTS). Substantial, stringently timed fluctuations in the number and localization of pfMACs were first observed long ago during murine HF morphogenesis and cycling. This already suggested some involvement of these innate immunocytes, with a recognized role in tissue remodelling and in hair growth control. The relatively recent demonstration of a Wnt signalling‐driven crosstalk between these immunocytes and HF epithelial stem cells in telogen HFs, which promotes anagen induction, has reinvigorated interest in the role that pfMAC plays in hair biology. Besides the apoptosis‐associated secretion of stem cell–activating Wnts and the differential secretion of HF‐targeting growth factors such as FGF‐5 and FGF5s from pfMACs, we also explore how MAC polarization, and thus function, may be influenced by the local metabolic and immune environment. Moreover, we examine how pfMACs may contribute to hair cycle–associated angiogenesis, vascular remodelling, HF immune privilege and immunopathology. On this basis, we discuss why targeting pfMACs may be relevant in the management of hair growth disorders. Finally, we argue that studying pfMACs offers an excellent, clinically relevant model system for characterizing and experimentally manipulating MAC interactions with an easily accessible mammalian, continuously remodelled (mini‐)organ under both physiological and pathological conditions.

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Clinicopathologic Characteristics and Response to Treatment of Persistent Chemotherapy-Induced Alopecia in Breast Cancer Survivors

Bhoyrul

Asfour

Lutz³

et al. 2021

JAMA Dermatol

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IMPORTANCE Alopecia induced by classic chemotherapy affects up to 65% of patients and is usually reversible. However, there are increasing reports of persistent chemotherapy-induced alopecia (pCIA), especially for patients treated with taxane-containing chemotherapy regimens.OBJECTIVE To analyze the clinicopathologic characteristics and response to treatment of patients with pCIA after chemotherapy for breast cancer.DESIGN, SETTING, AND PARTICIPANTS In this case series, a retrospective evaluation was performed of patients with a diagnosis of pCIA after chemotherapy for breast cancer in 4 specialist hair clinics from November 1, 2011, to February 29, 2020.MAIN OUTCOMES AND MEASURES Clinical, trichoscopic, and histopathologic characteristics and treatment outcomes were analyzed. For patients who presented with diffuse alopecia or diffuse rarefaction of hair over the midfrontal scalp with widening of the central part line and preservation of the frontal hairline, the Sinclair scale (grades 1-5, where 1 indicates normal hair density and 5 indicates the most severe stage of hair loss, with little or no hair in the centroparietal region) was used to assess severity. RESULTSOne hundred patients (99 women [99%]; mean age at presentation, 54.0 years [range, 29.0-74.1 years]) were included. Most patients had diffuse nonscarring alopecia (n = 39), female pattern hair loss (n = 55), or male pattern hair loss (n = 6). Six patients developed cicatricial alopecia. Taxane-containing regimens were used for most patients (92 [92%]) and were associated with more severe alopecia than regimens that did not contain taxanes (median Sinclair grade, 4 [IQR, 3-5] vs 2 [IQR, 2-2.5]; P < .001). A total of 76 of 86 patients (88%) had trichoscopic signs indistinguishable from those of androgenetic alopecia. Of 18 patients who had biopsies, 14 had androgenetic alopecia-like features, 2 had cicatricial alopecia, and 2 had features of both. Both topical and oral minoxidil, sometimes combined with antiandrogen therapy, were associated with an improvement in hair density (median Sinclair grade, 4 [IQR, 3-5] before treatment vs 3 [IQR, 2-4] after treatment; P < .001).CONCLUSIONS AND RELEVANCE This case series outlines previously unreported features of pCIA in patients with breast cancer, including a trichoscopic description. Cosmetically significant regrowth was achieved for a significant proportion of patients with topical or systemic treatments, suggesting that pCIA may be at least partly reversible.

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Lichen Planopilaris and Frontal Fibrosing Alopecia as Model Epithelial Stem Cell Diseases

Cited by 91 publications

References 97 publications

The role of the microbiome in scalp hair follicle biology and disease

The role of the microbiome in scalp hair follicle biology and disease

Hair growth control by innate immunocytes: Perifollicular macrophages revisited

Clinicopathologic Characteristics and Response to Treatment of Persistent Chemotherapy-Induced Alopecia in Breast Cancer Survivors

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