Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia

Aguh, Crystal; Dina, Yemisi; Talbot, C. Conover; Garza, Luis A.

doi:10.1016/j.jaad.2018.05.1257

Cited by 34 publications

(38 citation statements)

References 68 publications

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“…Here, the Treg-mediated transforming growth factor (TGF)-b signalling working to suppress ongoing inflammation appears also to drive fibrosis by EMT, 41 a process also recently identified in LPP and FFA. 31,42,43 Therefore, these data encourage further exploration of the role of Tregs in the pathogenesis of LPP and FFA, particularly around CD39 expression, TGF-b signalling and their role in EMT.…”

Section: Discussionmentioning

confidence: 81%

Profiling the human hair follicle immune system in lichen planopilaris and frontal fibrosing alopecia: can macrophage polarization differentiate these two conditions microscopically?

et al. 2020

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Summary Background Frontal fibrosing alopecia (FFA) is traditionally regarded as a variant of lichen planopilaris (LPP) based on histological features. Distinct clinical presentation, demographics and epidemiology suggest that differing pathogenic factors determine the final phenotype. Objectives To map the hair follicle immune system in LPP and FFA by systematically comparing key inflammatory markers in defined hair follicle compartments. Methods Lesional scalp biopsies from LPP and FFA and healthy controls were stained with the following immunohistochemical markers: CD1a and CD209, CD4, CD8, CD56, CD68, CD123, CXCR3, forkhead box (FOX)P3, mast cell tryptase and cKit. Macrophage polarization was explored using CD206, CD163, CD86, receptor for advanced glycation end products (RAGE), interleukin (IL)‐4 and IL‐13 on paired lesional and nonlesional LPP and FFA samples. Results Increased numbers of CD8+, CXCR3+ and FOXP3+ T cells and CD68+ macrophages were identified in the distal hair follicle epithelium and perifollicular mesenchyme in both LPP and FFA compared with controls. In both LPP and FFA, total and degranulated mast cells and CD123+ plasmacytoid dendritic cells were increased in the perifollicular mesenchyme adjacent to the bulge and infundibulum, whereas numbers of CD1a+ and CD209+ dendritic cells were significantly reduced in the infundibulum connective tissue sheath. However, only with CD68 staining was a significant difference between LPP and FFA identified, with greater numbers of CD68+ cells in LPP samples. Furthermore, the identified macrophage polarization markers downregulated CD86 and upregulated CD163 and IL‐4 expression in lesional LPP compared with FFA samples. Conclusions This comparative immunopathological analysis is the first to profile systematically the hair follicle immune system in LPP and FFA. Our analysis highlights a potential role of macrophages in disease pathobiology and suggests that macrophage polarization may differ between LPP and FFA, allowing microscopic differentiation. Linked Comment: Kinoshita‐Ise. Br J Dermatol 2020; 183:419–420.

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Section: Discussionmentioning

confidence: 81%

Profiling the human hair follicle immune system in lichen planopilaris and frontal fibrosing alopecia: can macrophage polarization differentiate these two conditions microscopically?

et al. 2020

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“…Two forms of cicatricial hair loss are increasing in frequency, central centrifugal cicatricial alopecia (CCCA) and frontal fibrosing alopecia (FFA). CCCA and FFA have epidemiologic features such as gender, racial predominance, scalp site specificity and an association with the reproductive axis that are suitable for longitudinal database modeling [1][2][3]. In this study, both African American and Caucasian women with cicatricial hair loss had a higher risk of hypertension.…”

Section: Introductionmentioning

confidence: 77%

Hypertension and Cicatricial Hair Loss: Defining High Value Symptom Clusters within Reproductive Aging

Colleen¹

2021

J Dermatol Res Ther

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common in Caucasian women, appears near the menopausal transition or beyond, and affects the eyebrows and frontal hairline [7-10]. Targeted destruction of the pilosebaceous unit in women during reproductive aging may share proinflammatory mechanisms with hypertension. Methods This study received approval from the University of Missouri Kansas City Institutional Review Board and informed written consent was obtained from all patients. Age, BMI, race, type of hair loss, systolic and diastolic blood pressure readings and presence of antihypertensive medication were collected from each patient. Blood pressure readings were taken at every visit, in the seated position, in one arm via an automated cuff. All but one patient was seen multiple times. The highest blood pressure reading across multiple visits was recorded. Data from 43 women with scarring hair loss was collected. 22 African American women with CCCA and 21 Caucasian women with FFA were compared to an age, race and BMI matched group of women without hair loss. The control group originated from the same clinic. To support randomness in the control group, data was collected from women attending clinic on the 1 st , 15 th and 30 th days of the month. Descriptive statistics, such as mean, standard deviation and proportion were calculated to describe our sample. T tests were conducted to estimate and test group difference on the outcome variables. Statistical analyses were conducted using SPSS version 24. Results Both study groups had a mean systolic pressure of

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“…[ 14 ] While the increased association of CCCA with previous pregnancies is a novel, previously unreported finding, the results from Aguh's study also indirectly point to a hormonal link due to the increased prevalence of uterine leiomyomas. [ 3 ] Uterine fibroids are benign tumors of the myometrium which have been found to be hormonally linked to estrogen: estrogen causes upregulation of progesterone receptor expression which then results in fibroid proliferation. [ 15 16 17 ] In general, the prevalence of fibroids ranges from 4.5% to 68.6% depending on diagnostic methodology, and women are usually diagnosed with fibroids around the age of 50 years.…”

Section: Discussionmentioning

confidence: 99%

“…[ 1 2 ] A recent publication demonstrated the upregulation of specific fibroproliferative genes in these women and another identified a common mutation in the PADI3 gene of hair-shaft formation. [ 3 4 ]…”

Section: Introductionmentioning

confidence: 99%

Increased association between previous pregnancies and use of chemical relaxers in 74 women with central centrifugal cicatricial alopecia

et al. 2020

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Background: Central centrifugal cicatricial alopecia (CCCA) is a type of scarring alopecia exclusively seen in women of African descent. The etiology is unknown and epidemiologic studies including data on comorbidities in patients with CCCA are limited. Our primary objective was to identify possible etiologic and lifestyle associations in patients with CCCA. Materials and Methods: A retrospective chart review was conducted for patients diagnosed with CCCA between January 1, 2013, and January 1, 2018, at a university dermatology outpatient clinic. Controls consisted of age-, sex-, and race-matched African–American women diagnosed with other hair loss conditions. Data from 74 cases and 96 controls were collected and analyzed via logistic regression. In addition, a phone survey was conducted in the CCCA cohort asking specific questions related to their condition and quality of life. Results: A significant relationship was found between CCCA and previous pregnancies as well as the use of chemical relaxers: patients with CCCA were 11.71 times more likely to have had a previous pregnancy ( P < 0.001) and 12.37 times more likely to have used chemical relaxers in the past ( P < 0.001). Association with uterine fibroids was found not statistically significant ( P > 0.05). Conclusion: We identified an association between previous pregnancies and use of chemical relaxers in patients diagnosed with CCCA when compared to controls. These findings may help to plan prospective studies aiming at establishing a more concrete link between hormones and CCCA.

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Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia

Abstract: We have identified the upregulation of critical genes implicated in FPDs in the gene expression profile of patients with CCCA. These findings may help identify future therapeutic targets for this otherwise difficult-to-treat condition.

Cited by 34 publications

References 68 publications

Profiling the human hair follicle immune system in lichen planopilaris and frontal fibrosing alopecia: can macrophage polarization differentiate these two conditions microscopically?

Profiling the human hair follicle immune system in lichen planopilaris and frontal fibrosing alopecia: can macrophage polarization differentiate these two conditions microscopically?

Hypertension and Cicatricial Hair Loss: Defining High Value Symptom Clusters within Reproductive Aging

Increased association between previous pregnancies and use of chemical relaxers in 74 women with central centrifugal cicatricial alopecia

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