JAMA dermatology最新文献

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.

Importance: Nail lichen planus has the potential to cause permanent destruction of the nail unit and remains challenging to treat. Studies suggest that low-dose naltrexone is a safe and potentially effective treatment for other dermatologic conditions, including lichen planopilaris.

Objective: To assess the effectiveness of low-dose naltrexone in treating nail lichen planus.

Design, setting, and participants: This case series evaluates 7 adult patients with biopsy-proven nail lichen planus who were treated with low-dose naltrexone (3 mg per day) at the University of Miami dermatologic clinics from November 2022 to December 2023. The data were analyzed in March 2024. Patients were treated for at least 2 months and had in-person follow-up evaluation while receiving treatment.

Main outcomes and measures: The main outcome was posttreatment clinical nail lichen planus severity index, which was scored as clear, mild, moderate, or severe. Patients were evaluated for oral and cutaneous disease during the course of treatment. Tolerance and adverse events were noted.

Results: A total of 7 patients (mean [range] age, 60 [38-77] years; 3 female individuals) were included. All but 1 patient had been previously treated and did not respond to at least 1 prior treatment (median [range], 2.5 [0-4.0] treatments). Treatment duration ranged from 2 to 11 months. Clinical response was observed in 4 of 7 patients, with an overall 35% reduction in nail lichen planus severity index. Two patients with severe disease achieved a reduction to mild severity. None of the patients had to discontinue low-dose naltrexone due to adverse events, and no adverse events were reported.

Conclusions and relevance: The results of this study suggest that low-dose naltrexone may be a therapeutic approach for treating nail lichen planus. Further controlled studies are warranted to better understand its clinical efficacy and safety profile in treating nail lichen planus.

Importance: There is poor accuracy and reproducibility for the histopathologic diagnosis of melanocytic skin lesions, and the provision of clinical information may improve this.

Objective: To examine the impact of clinical information on the histopathologic diagnosis of melanocytic skin lesions.

Evidence review: PubMed, Embase, and Cochrane Library were searched for new records published from January 2018 to January 2024. References included in the 2018 Cancer Council Australia evidence review were also screened, and forward and backward citation searches were conducted.

Findings: From 2224 records screened, 162 full-text studies were assessed, and 7 studies were included. Studies included pathologists from Austria, Germany, the US, Italy, the UK, and Australia. Patient populations had a mean age of 43 to 55 years and a proportion of female participants of 23% to 63%. The risk of bias assessment demonstrated that all studies had domains at unclear or high risk of bias. Clinical images increased diagnostic certainty (3 studies) and agreement between pathologists (2 studies) led to diagnostic upgrades in 7.6% to 16.7% of interpretations. Clinical diagnosis on the pathology requisition form reduced the odds of missing a melanoma with progression (1 study), while more clinical elements on the form correlated with higher re-excision rates (1 study). Among patients with distant metastases on long-term follow-up, a prior consensus diagnosis of melanoma was established on histopathology alone.

Conclusions and relevance: Providing clinical information to pathologists may improve diagnostic confidence and interobserver agreement and result in upgrading of the histopathologic diagnosis. While providing the clinical diagnosis may prevent missing a progressive melanoma, more research is needed to determine the appropriateness of histopathology upgrading when clinical images are provided and the impacts on patient outcomes.

Importance: Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience neuropathic pain and itch. There is a lack of evidence on any treatment for these symptoms in patients with RDEB.

Objectives: To test the efficacy of pregabalin in the treatment of neuropathic pain and itch in patients with RDEB.

Design, setting, and participants: A randomized, double-blinded, crossover trial of oral pregabalin (50-300 mg/d) vs placebo was conducted at 2 sites, Toronto (Canada) and Santiago (Chile) from January 1, 2019, to December 31, 2020. Patients eligible to participate were diagnosed with RDEB, aged 8 to 40 years, not pregnant or lactating (if female), and had evidence of probable neuropathic pain and itching defined as distal thermal sensory loss (confirmed by thermal roller), score of 4 or greater on the Douleur Neuropathique 4 questionnaire (DN4), and score greater than 4 on the 10-point visual analog scale [VAS]). Patients with a clinically important or poorly controlled medical or psychiatric condition or pregabalin intolerance or allergy were excluded. Of 41 patients screened, 3 were not eligible and 28 declined enrollment. Data analyses were performed in 2021 through 2023.

Intervention: Participants received both pregabalin and matched placebo (titrated to a maximum-tolerated dose of 300 mg/day) in a randomized sequence so that comparisons could be made within participants and between groups.

Main outcomes and measures: Difference in the mean pain and itch scores between pregabalin and placebo treatment (measured using VAS) before and after intervention.

Results: In all, 10 participants were randomized to 2 groups, 6 patients (mean [SD] age, 26.7 [8.1] years; 3 females [50%]) in group 1, and 4 patients (mean [SD] age, 26.5 [7.8] years, 2 females [50%]) in group 2. Group 1 received a sequence of pregabalin-placebo while group 2 received placebo-pregabalin. Pregabalin significantly reduced mean (SD) pain scores by 1.9 (1.5) points when controlling for sequence and treatment period vs baseline, while placebo had 0.1 (2.0) points of reduction. The effect of pregabalin was a mild but significant reduction in itch compared to baseline (mean [SD] points, 0.9 [2.2]), whereas the placebo produced no reduction (0.1 [2.5]). The mean pregabalin dose was generally well tolerated.

Conclusions and relevance: The results of this randomized crossover trial indicate that pregabalin significantly reduced pain and itch scores from baseline compared to placebo in patients with RDEB. This feasibility study provided preliminary data on the efficacy of pregabalin in managing pain and itch in RDEB and gathered essential data to inform the design of a larger cohort trial.

Trial registration: ClinicalTrials.gov Identifier: NCT03928093.