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

Jamerson, Taylor A.; Talbot, C. Conover; Dina, Yemisi; Kwatra, Shawn G.; Garza, Luis A.; Aguh, Crystal

doi:10.1111/exd.14524

Cited by 7 publications

(1 citation statement)

References 22 publications

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“…A disruption of pro-inflammatory and anti-inflammatory factors has also been noted to contribute to the pathogenesis. For example, matrix metalloproteinase 9 (MMP9) is a biomarker associated with dysregulated pathways of fibrosis and is upregulated in severe cases of CCCA [18]. This dysregulation is translated clinically by the low-grade inflammation seen on dermoscopy and histopathology with the subsequent progression to fibrosis [15].…”

Section: Aetiologymentioning

confidence: 99%

Central Centrifugal Cicatricial Alopecia in the Adolescent Population: An Overview of Available Literature

Palmer

Valdebran

2023

Life

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Central centrifugal cicatricial alopecia (CCCA) is a lymphocytic scarring alopecia that predominantly affects women of African descent. Recent studies have demonstrated prevalence in children and adolescents, as well as Asian populations. A thorough search of Pubmed, Cochrane Database of Systematic Reviews, OVID Medline and Google Scholar was conducted using keywords such as “central centrifugal cicatricial alopecia”, “scarring hair loss”, “scarring alopecia”, “hot comb alopecia”, “pediatric” and “adolescent”. The results yielded few articles in the literature that directly addressed CCCA in the adolescent population, with three articles providing details of the presentation in the form of case series and retrospective reviews. The presentation in the adolescent population was found to be varied, ranging from asymptomatic to symptomatic and involving diffuse to patchy hair loss in only the vertex and/or frontal and parietal scalp. Genetic and environmental etiologies were found to be statistically significant, and markers of metabolic dysregulation predisposing patients to diabetes mellitus and breast cancer were also uncovered. The differential diagnosis of patients who present with hair loss in the adolescent population should therefore be broad, and a low threshold for biopsies should be adopted to confirm CCCA in suspected patients. This will have future implications for reduced morbidity and public health.

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Section: Aetiologymentioning

confidence: 99%

Central Centrifugal Cicatricial Alopecia in the Adolescent Population: An Overview of Available Literature

Palmer

Valdebran

2023

Life

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Low-Dose Metformin and Profibrotic Signature in Central Centrifugal Cicatricial Alopecia

Bao,

Qadri,

Gadre

et al. 2024

JAMA Dermatol

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ImportanceCentral centrifugal cicatricial alopecia (CCCA) is a scarring alopecia predominantly affecting Black female individuals. Current conventional treatments target inflammation but not the underlying fibrotic processes, often leading to permanent hair loss.ObjectiveTo investigate the associations of low-dose oral metformin, an antidiabetic medication with antifibrotic properties, with clinical symptoms and scalp gene expression patterns in patients with CCCA.Design, Setting, and ParticipantsThis retrospective clinical case series and transcriptomic analysis included patients treated at a single tertiary academic medical center between January 2023 and March 2024. All patients had biopsy-confirmed CCCA refractory to standard treatments. Transcriptomic analysis was performed on patients with previously banked, paired scalp biopsies before and after treatment with adjuvant metformin for at least 6 weeks.ExposureExtended-release metformin, 500 mg, once daily was added to participants’ baseline CCCA treatment regimens.Main Outcomes and MeasuresClinical assessments included pruritus, inflammation, scalp resistance, and hair regrowth. Gene expression profiling via bulk RNA sequencing analysis evaluated differential gene expression and pathway enrichment.ResultsA total of 12 Black female participants were included in the study, and transcriptomic analysis was performed in 4 participants. After at least 6 months of metformin treatment, 9 participants experienced improvement in disease, including scalp pain, inflammation, and/or pruritus, and 6 demonstrated clinical evidence of hair regrowth. The addition of metformin led to reversal of many prominent gene pathways previously identified in CCCA. Transcriptomic analysis revealed upregulation of pathways and genes (keratin-associated proteins [KRTAPs]) involved in keratinization, epidermis development, and the hair cycle (absolute log2-fold change &gt; 4), with concomitant downregulation of fibrosis-related pathways and genes (eg, MMP7, COL6A1) (fold change &gt;1.5; all false discovery rate &lt;.05). Gene set analysis showed reduced expression of helper T cell 17 and epithelial-mesenchymal transition pathways and elevated adenosine monophosphate kinase signaling and KRTAPs after metformin treatment.Conclusions and RelevanceIn this case series of patients with treatment-refractory CCCA, low-dose oral metformin was associated with symptomatic improvement and dual modulation of gene expression, stimulating hair growth pathways while suppressing fibrosis and inflammation markers. These findings provide a rationale for future clinical trials studying metformin as a targeted therapy for CCCA and other cicatricial alopecias.

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Letter from the editor: Making sense of central centrifugal cicatricial alopecia

Elston,

Elewski,

Taylor

2024

Journal of the American Academy of Dermatology

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

Cited by 7 publications

References 22 publications

Central Centrifugal Cicatricial Alopecia in the Adolescent Population: An Overview of Available Literature

Central Centrifugal Cicatricial Alopecia in the Adolescent Population: An Overview of Available Literature

Low-Dose Metformin and Profibrotic Signature in Central Centrifugal Cicatricial Alopecia

Letter from the editor: Making sense of central centrifugal cicatricial alopecia

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