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Importance: Central 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. Objective: To 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 Participants: This 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. Exposure: Extended-release metformin, 500 mg, once daily was added to participants' baseline CCCA treatment regimens. Main Outcomes and Measures: Clinical assessments included pruritus, inflammation, scalp resistance, and hair regrowth. Gene expression profiling via bulk RNA sequencing analysis evaluated differential gene expression and pathway enrichment. Results: A 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 > 4), with concomitant downregulation of fibrosis-related pathways and genes (eg, MMP7, COL6A1) (fold change >1.5; all false discovery rate <.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 Relevance: In 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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Introduction Dermabrasion and chemical peels are infrequently utilized methods of treatment for medical-grade conditions despite demonstrations of favorable outcomes. Insurance coverage status has previously been shown to impact availability and accessibility to specific treatments. The purpose of this study is to evaluate the rate of insurance coverage provided for dermabrasion and chemical peel procedures in the treatment of acne, acne scarring, and non-melanoma skin cancers (NMSC). Methods A cross-sectional analysis of 58 insurance companies by web-based search or phone interview determined the number of insurers with a publicly available policy on dermabrasion or chemical peels. Coverage status and any corresponding criteria were extracted from existing company policies. Results Thirteen (22%) and 22 (38%) policies discussed dermabrasion in the treatment of basal cell carcinoma and actinic keratosis, with 62% and 73% of these policies providing coverage. Acne scarring was discussed in significantly more dermabrasion policies than basal cell carcinoma (45% vs 22%; p=0.018). However, significantly more insurers denied coverage of dermabrasion for active acne and acne scarring when compared to dermabrasion to treat basal cell carcinoma or actinic keratosis (p<0.001). Eighty-seven percent of companies (n=20) with a chemical peel policy for premalignant lesions would provide coverage, with required criteria present in 95% (n=19) of the policies that would cover chemical peels for actinic keratosis specifically. Of the 25 companies (43%) that discussed the treatment of acne with chemical peel procedures, 14 (56%) provided coverage, and 11 (44%) denied coverage. Coverage was denied by significantly less insurers for the treatment of active acne with chemical peel procedures compared to treatment with dermabrasion (44% vs 83%; p<0.006). Conclusion Significant discrepancies were noted in both the presence of a public policy and the coverage status of dermabrasion or chemical peel procedures among the United States health insurance companies. These inconsistencies, along with multiple criteria required for coverage, may create an artificial barrier to receiving care for specific medical-grade conditions.
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Traumatic brain injury resulting from exposure to blast overpressure (BOP) is associated with neuropathology including impairment of the blood-brain barrier (BBB). This study examined the effects of repeated exposure to primary BOP and post-blast treatment with an antioxidant, N-acetylcysteine amide (NACA) on the integrity of BBB. Anesthetized rats were exposed to three 110 kPa BOPs separated by 0.5 h. BBB integrity was examined in vivo via a cranial window allowing imaging of pial microcirculation by intravital microscopy. Tetramethylrhodamine isothiocyanate Dextran (TRITC-Dextran, mw = 40 kDa or 150 kDa) was injected intravenously 2.5 h after the first BOP exposure and the leakage of TRITC-Dextran from pial microvessels into the brain parenchyma was assessed. The animals were randomized into 6 groups (n = 5/group): four groups received 40 kDa TRITC-Dextran (BOP-40, sham-40, BOP-40 NACA, and sham-40 NACA), and two groups received 150 kDa TRITC-Dextran (BOP-150 and sham-150). NACA treated groups were administered NACA 2 h after the first BOP exposure. The rate of TRITC-Dextran leakage was significantly higher in BOP-40 than in sham-40 group. NACA treatment significantly reduced TRITC-Dextran leakage in BOP-40 NACA group and sham-40 NACA group presented the least amount of leakage. The rate of leakage in BOP-150 and sham-150 groups was comparable to sham-40 NACA and thus these groups were not assessed for the effects of NACA. Collectively, these data suggest that BBB integrity is compromised following BOP exposure and that NACA treatment at a single dose may significantly protect against blast-induced BBB breakdown.