JAMA dermatology最新文献

Importance: Over the past decades, many global regions have experienced a steady increase in the incidence of cutaneous melanoma. However, more recently, a downward trend has been observed in the younger age groups in Australia and the US. Yet, in Europe, none of the countries have reported any significant decline in melanoma incidence for any age group.

Objective: To assess melanoma incidence and mortality trends in Sweden, with a focus on individuals younger than the average age of melanoma onset.

Design, setting, and participants: This cohort study used data on the national population from the Swedish Melanoma Registry and the Swedish Cancer Registry, which cover more than 99% of all primary invasive cutaneous melanomas diagnosed in the country. All patients diagnosed from 1990 to 2022 were included.

Main outcomes and measures: Incidence and mortality rates per 100 000 inhabitants were calculated for each year and shown as average annual rates for every 5-year period from 1990 to 2022. Joinpoint regression models were used to evaluate statistical significance of temporal trends and points of change.

Results: There were 34 800 primary invasive cutaneous melanomas (19 582 [56.3%] in females and 15 218 [43.7%] in males) reported in 33 324 individuals younger than 60 years (median [IQR] age, 48 [36-58] years) from 1990 to 2022. A consistent rise in melanoma incidence was observed among those 50 to 59 years old. The age groups from 20 to 29 years, 30 to 39 years, and 40 to 49 years showed an incidence peak in 2013 to 2015 followed by stable or significantly declining rates until 2022. In patients younger than 20 years, melanoma incidence remained low with no significant trends. There was also a significant decline in melanoma mortality among 30- to 59-year-old individuals, but not in those 60 years and older.

Conclusions and relevance: The findings of this cohort study showed a significant recent downward trend in both melanoma incidence and melanoma mortality in the age group 30 to 49 years in Sweden. The reasons for these declines are unclear but may include UV protection, public health campaigns, changing population demographics, and the introduction of effective melanoma treatment. None of these possibilities were evaluated; further study is needed.

Importance: US veterans may be at an increased risk of developing various dermatologic conditions compared with nonveterans.

Objectives: To compare the prevalence and the odds of dermatologic conditions (eg, skin cancers, dermatitis/eczema/rash, psoriasis) between veterans and nonveterans.

Design, setting, and participants: This population-based cross-sectional study leveraged nationally representative data from the National Health and Nutrition Examination Survey (NHANES). Three questionnaires (demographics, medical conditions, and dermatology) were merged from 1999-2018 for analysis. Participants were nonveterans and veterans from NHANES data. Data were analyzed from August 2023 to April 2024.

Main outcomes and measures: The prevalence and odds ratios (ORs) comparing veterans and nonveterans were examined for various dermatologic conditions, including self-reported skin cancer history (any skin cancer, melanoma, nonmelanoma and unknown subtypes), dermatitis/eczema/inflamed rash, and psoriasis.

Results: In a total of 61 307 participants (54 554 nonveterans and 6753 veterans), there was a higher prevalence of any skin cancer history among US veterans compared with nonveterans (9.0% vs 2.9%; P < .001) as well as a higher prevalence of melanoma history (2.2% vs 0.6%; P < .001). Adjusted for demographic factors, veterans had higher odds of any skin cancer history (OR, 1.72; 95% CI, 1.23-2.40) and higher odds of a melanoma history (OR, 2.27; 95% CI, 1.17-4.39) compared with nonveterans. Veterans had a higher prevalence of a psoriasis diagnosis compared with nonveterans (4.5% vs 2.9%; P = .002) and a 61% higher odds of a psoriasis diagnosis (OR, 1.61; 95% CI, 1.05-2.46) compared with nonveterans.

Conclusions and relevance: This cross-sectional study found that veterans have higher prevalence and odds of various dermatologic conditions compared with nonveterans. Efforts aimed at improving health care quality among veterans must investigate the underlying causes of worsened skin health in this population.

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.