Faculty Bibliography

Alopecia areata (AA) is a common autoimmune condition that affects approximately 2% of the global population. Although it most commonly presents with the abrupt onset of well-circumscribed, non-scarring alopecic patches on the scalp, the nails and other hair-bearing areas are also frequently affected. Clinical evaluation should document disease extent and employ trichoscopy to identify characteristic signs of the condition (e.g., black-dot hairs, exclamation point hairs). The Severity of Alopecia Tool (SALT) is standard for quantifying severity, and newer instruments like the Alopecia Areata Severity Scale (AASc) incorporate extra-scalp involvement and psychosocial burden. Moreover, machine learning approaches and validated patient-reported outcome measures, such as the Alopecia Areata Patient Priority Outcomes (AAPPO), have emerged that can standardize assessment and longitudinal tracking. AA prognosis is influenced by several factors, including age, disease subtype, extent and duration of hair loss, and family history. Pathogenesis is heterogeneous, multifactorial, and includes the collapse of immune privilege with cytotoxic CD8+ T cell inflammation. Genetic and pharmacologic data support a key role for the JAK/STAT pathway and demonstrate that Th2-related inflammation is involved in select patients. The quality-of-life impact of AA and associated comorbidities are substantial.

BACKGROUND:Transcriptome-wide association studies (TWAS) identify genetically regulated expression (GReX) components and can pinpoint causal genes in genome-wide association studies but are often limited by a single-cell context. OBJECTIVE:We hypothesized that modeling GReX across multiple conditions could enhance power to identify causal genes for complex inflammatory diseases. METHODS:We conducted TWAS on 400 transcriptomes under 8 proinflammatory cytokine stimulations in keratinocytes, modeling GReX for 18,599 genes against genome-wide association studies from 7 inflammatory skin diseases: atopic dermatitis, psoriasis, acne, alopecia areata, systemic sclerosis, systemic lupus erythematosus, and vitiligo. RESULTS:), and our method successfully captured >85% of all genes with colocalizing expression quantitative trait loci. Single-cell-resolution spatial profiling further demonstrated the modulation of TWAS signals in keratinocytes by close proximity to TNF/IL-17-expressing cells in psoriatic skin. CONCLUSION/CONCLUSIONS:Modeling gene expression across relevant cellular states substantially improves the power and resolution of TWAS.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with marked clinical heterogeneity and a multifactorial pathogenesis. Environmental and lifestyle factors, including obesity, tobacco exposure, microbiome dysbiosis, dietary patterns, and plastic-associated endocrine disruptors, have all been linked to HS risk or disease severity. However, these exposures alone do not fully explain why only some individuals develop HS, why age at onset and severity vary substantially, or why disease occurs in patients without major identifiable environmental burden. In parallel, genetic studies have demonstrated that inherited susceptibility is a central component of HS pathogenesis. Rare loss-of-function variants in γ-secretase complex genes cause a small subset of familial, autosomal dominant HS, while genome-wide association studies have shown that population-level risk implicates pathways involved in epithelial differentiation, follicular biology, immune signaling, and cutaneous inflammation. Recent work further suggests that common and rare genetic risk may converge on shared biological mechanisms, including γ-secretase-related signaling. While nature vs. nurture arguments dichotomize genetic constitution and environmental exposures, current evidence supports a model in which genetic susceptibility interacts with environmental exposures to shape HS risk, clinical expression, and disease progression. In this review, we examine the evidence supporting both exposomic and genomic contributions to HS and argue that the disease is best understood as arising from their intersection rather than from either domain alone.

Hidradenitis suppurativa (HS) is a prevalent, debilitating disease affecting ~1% of the population, with limited therapeutic options and poor long-term remission rates. HS arises from inflammation and destruction of apocrine-bearing hair follicles, suggesting a multifactorial pathology involving immune dysregulation and follicular dysfunction. Emerging treatment strategies largely center on immune suppression, with three FDA-approved therapies targeting inflammatory pathways. However, most patients fail to achieve durable remission. Genetic evidence increasingly implicates the hair follicle as a key contributor to HS pathogenesis. For example, genes that cause ectodermal dysplasias (EDs) have been implicated by common risk variants identified in genome-wide association studies (GWAS) and by rare variants in sequencing studies of rare ED syndromes that co-present with HS. EDs are Mendelian (i.e., single-gene) disorders that disrupt the development of ectodermal derivatives, including hair follicles and sweat glands. The enrichment of ED-associated genes in HS genetic studies, together with HS phenotypes observed in ED patients, supports a critical role for aberrant follicular development in HS pathogenesis. We propose that HS represents a spectrum of related diseases entities spanning immune dysregulation and hair follicle pathology, underscoring the need for biomarkers and refined disease classification to tailor treatment strategies. This perspective argues for broadening drug-development programs and insurance coverage for therapeutic strategies beyond immunomodulation to include follicle-targeted approaches.

Platelet-rich plasma (PRP) injections are an effective and increasingly utilized treatment for androgenetic alopecia; however, the delivery of concentrated growth factors raises theoretical concerns regarding cutaneous malignancy risk in chronically ultraviolet (UV)-exposed, hair-thinning scalps. In this article, the current hypotheses linking PRP to scalp skin cancer risk are reviewed, including potential oncogenic mechanisms, such as platelet-derived growth factor (PDGF)-mediated signaling, and protective effects, such as improved hair-mediated photoprotection and antiproliferative findings from related blood products, although direct PRP-specific data remain lacking. Overall, the available evidence supports PRP safety while underscoring the need for prospective studies, routine scalp surveillance, and patient counseling regarding photoprotection.