Evolving treatment paradigms in dermatology: Insights from emerging and repurposed therapies

In real-world clinical practice, dermatologists encounter a wide spectrum of skin disorders with substantial heterogeneity in pathogenesis, severity, and clinical course. Despite significant advances in the understanding and management of dermatological diseases over recent decades, effective therapeutic options remain limited for a number of conditions. For certain diseases, currently available treatments demonstrate suboptimal efficacy; for others, clinical application is constrained by insufficient supporting evidence, reliance on small case series or anecdotal reports, or off-label application due to the absence or infeasibility of clinical trials.1 These therapeutic gaps underscore substantial unmet clinical needs in dermatology. To address these challenges, dermatologists are committed to conducting rigorous clinical and translational research aimed at identifying novel treatment strategies and evaluating their efficacy and safety. Such efforts are essential to expanding the therapeutic armamentarium and improving patient outcomes. In this issue of Dermatologica Sinica, we present a series of studies that explore emerging therapeutic approaches across a range of dermatological diseases. Mahawar and Deshmukh conducted a randomized controlled trial demonstrating that 6 months of low-dose oral minoxidil treatment (1.25 and 2.5 mg daily) increased terminal hair density in patients with androgenetic alopecia (AGA), with efficacy comparable to topical 5% minoxidil solution twice a day.2 These findings provided evidence supporting an alternative route of administration and dose of minoxidil for AGA.2 Phototherapy is a major treatment modality for vitiligo,3 however, optimal ultraviolet B treatment protocol and parameters remained elusive. Yang et al. performed a single-center cross-sectional study to show that, in addition to wavelength and fluence, irradiance is a crucial factor affecting phototherapy outcomes. High irradiance excimer light induced repigmentation at lower fluence compared to low irradiance.4 These findings may assist dermatologists in selecting and optimizing phototherapy strategies for patients with vitiligo. Immune-mediated inflammatory diseases exhibit considerable heterogeneity in clinical presentation and disease course among individuals in real-world practice, reflecting the inherent plasticity of the immune system.5 Paradoxical reactions or phenotypic switching during or after treatment, multiple therapeutic failures, the presence of multiple comorbidities, and pediatric populations are not uncommon in daily clinical settings;6-9 however, such complex scenarios are often not investigated or excluded in clinical trials.1 In this issue, Tsai and Yu report that the Janus kinase inhibitor upadacitinib may represent a potential therapeutic option for biologic-related paradoxical reactions.10 Shen et al. demonstrate the potential efficacy of tofacitinib in the treatment of pediatric palmoplantar pustulosis.11 In addition, Chiang et al. suggest that dual targeted therapy may serve as a promising approach for patients with concomitant psoriasis and ulcerative colitis.12 The safety profile of a treatment is a critical consideration when evaluating the risk–benefit balance of therapeutic decision-making. Nevertheless, data derived from clinical trials may not fully recapitulate or representative of the adverse events in real-world clinical practice, owing to the limited duration of follow-up and the highly controlled conditions of trials.1 Safety data derived from real-world settings can complement and address the limitations of clinical trial data. Chiang et al. conducted a multicenter, retrospective cohort study, which showed mucositis and lichen planus were the predominant immune checkpoint inhibitors (ICI)-associated oral toxicities that usually onset at 77.6 days after ICI initiation.12 Ritchie and Espiridion, using the TriNetX network, provided evidence supporting that nonincreased risk of adverse psychiatric outcomes for patients taking isotretinoin compared to oral antibiotics.13 Collectively, these studies provide new insights into innovative therapeutic strategies through the repurposing of existing agents across different treatment paradigms and disease entities, and offer valuable evidence to inform dermatologists in real-world clinical practice. Data availability statement Data sharing is not applicable to this article as no datasets were generated or analyzed during the current article. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.