Faculty Bibliography

BACKGROUND:Lichen planopilaris (LPP) and folliculitis decalvans (FD) are two of the most common types of primary scarring alopecia. Several Janus kinase inhibitors (JAKis) have been used effectively in their treatment. We conducted an immunohistochemical (IHC) study to evaluate whether any member of the JAK family was overexpressed in the primary inflammatory infiltrate of FD and LPP. Additionally, we performed an exploratory retrospective study on the efficacy and safety of oral JAKis in LPP. METHODS:Pathology scalp samples from seven healthy controls and 28 patients with LPP or FD were selected for staining with anti-JAK1, anti-JAK2, anti-JAK3, and anti-TYK2 antibodies. Cases and controls were compared using the H-score of the inflammatory cells. On the other hand, an exploratory retrospective clinical study was conducted in which patients with LPP who were treated with JAKis for at least three months were included. Clinical characteristics, severity scores, and the presence of adverse events were collected. RESULTS:The IHC study determined that JAK1 and JAK2 exhibited similar expression patterns in cases and controls. However, JAK3 and TYK2 were expressed solely in cases of primary scarring alopecia and were negative in the controls. In the exploratory clinical study, 19 patients with LPP were treated with JAKis. Severity scores improved in follow-up visits, with adverse events generally being mild. CONCLUSIONS:JAK3 and TYK2 were overexpressed in LPP and FD samples compared to healthy controls, supporting JAKs as potential pharmacological targets of interest. JAKis could be an effective and safe treatment for LPP patients.

Performance-enhancing substances (PES) are used by many athletes worldwide to improve performance and enhance appearance. Although PES are more commonly used by men, use is increasing among women, leading to growing physical and psychosocial concerns. Illegal PES include androgenic and anabolic steroids (AAS), which represent a diverse class of synthetic derivatives of testosterone. PES use has been linked to an increased risk of cardiovascular, metabolic, endocrine, neurologic, infectious, hepatic, renal, and musculoskeletal disorders. Additionally, hormonal alterations secondary to PES use can induce or accelerate female pattern hair loss (FPHL). Despite the widespread prevalence of FPHL, research has disproportionately focused on male pattern hair loss (MPHL) and male athletes utilizing PES. This review article explores the pathophysiology of testosterone, gender-based AAS dosing implications, incidence of FPHL, physical and psychosocial impacts of alopecia, and management strategies. Though research regarding the impact of androgen-based PES on hair health exists, few studies address these issues in the context of female athletes. Importantly, clinicians must be equipped to provide female athletes with education regarding potential risks of AAS and to appropriately manage FPHL in this patient population. Furthermore, timely diagnosis and treatment of FPHL, alongside AAS cessation, are crucial to preventing further hair loss and optimizing the safety and efficacy of alopecia treatments. Given the compounded psychosocial concerns among female athletes worldwide on PES-including hair loss, body image insecurities, and even eating disorders-ongoing research in this area is critical.

Hair traits are nonpathogenic features that vary among individuals. Unlike hair follicle (HF) diseases, which are rare in the population, hair traits can be measured in everyone. This facilitates the construction of large cohorts that are well-powered for gene discovery. GWASs identify genetic variants that are widely shared among people globally, providing knowledge with broad population relevance. We compile findings from hair trait GWASs to deepen our understanding of HF biology. In reviewing genetic factors that influence hair traits, we demonstrate overlap with disease genes, underscoring that genetic studies of traits improve our knowledge about health and disease.

Despite the wide variety of treatment options for alopecia areata (AA), androgenetic alopecia (AGA), and primary cicatricial alopecias, these options become more limited for women who are breastfeeding, given concerns surrounding potential transfer into breast milk and subsequent adverse effects (AEs) on the newborn infant. Alopecia is associated with significant psychological distress, poorer quality of life (QOL), and negative impacts on self-esteem and body image, which may be exacerbated by undergoing the physical, hormonal, and emotional changes of pregnancy and breastfeeding. Furthermore, many of these medications must be taken continuously to maintain their benefits, reinforcing the importance of understanding which therapies are compatible with breastfeeding. This review aimed to help guide clinicians in choosing safe and appropriate hair loss therapies for women during lactation, including a detailed discussion of medication transfer to breast milk and infant blood serum levels, potential neonatal AEs, and further clinical considerations specific to each treatment option.

BACKGROUND:Persistent chemotherapy-induced alopecia (pCIA) is a distressing side effect of antineoplastic agents, imposing significant psychological burdens on cancer survivors. Despite its impact, there are no standardized guidelines for diagnosis, prevention or management. OBJECTIVES/OBJECTIVE:To establish consensus-based definitions, diagnostic criteria, grading systems and management recommendations for pCIA. METHODS:A two-round Delphi method was conducted with 15 international experts in supportive oncodermatology and hair diseases from both Europe and the Americas. Statements were rated on a 5-point Likert scale, with a strong consensus defined as ≥75% agreement. Statements that did not achieve strong consensus in the first round were revised based on expert feedback and re-evaluated in a second-round survey. RESULTS:Strong consensus was reached on 47 statements (75.8%). pCIA was defined as non-scarring alopecia persisting beyond 6 months post-chemotherapy. Causes were attributed to the destruction of hair follicle stem cells, with taxanes, thiotepa and anthracyclines identified as key contributors. Consensus emphasized the importance of prevention of pCIA through scalp cooling devices, and the early intervention with topical or low-dose oral minoxidil was also recommended. Interestingly, the experts did not recommend the use of bicalutamide, oral finasteride and dutasteride (including in mesotherapy) for breast cancer patients with pCIA, citing potential safety concerns. CONCLUSIONS:This Delphi study established unified guidelines for pCIA, providing clinicians with a clear framework for diagnosis and treatment. Highlighting prevention through scalp cooling and timely interventions may improve outcomes for cancer survivors. Further research is necessary to assess new treatments and the long-term impact of chemotherapy on hair follicles.

PURPOSE/OBJECTIVE:Chemotherapy-induced alopecia (CIA) affects approximately 65% of patients receiving chemotherapy and has a negative impact on quality of life (QoL). Scalp cooling (SC) is the only FDA-cleared intervention for CIA. This systematic review and meta-analysis evaluated SC adverse events (AEs), reasons for discontinuation, and scalp metastasis incidence. METHODS:Meta-analyses using random-effects models estimated pooled prevalences of SC AEs, SC discontinuation, and reasons for discontinuation. A generalized linear mixed model was used to estimate the incidence of scalp metastasis. RESULTS:Sixty-seven studies met the inclusion criteria. The most common AEs were generalized chills (42%, 95% confidence interval (CI) 26-58%), cap heaviness (35%, 95% CI 18-52%), and headache (30%, 95% CI 21-39%). The SC discontinuation rate was 18% (95% CI 13-23%). The most common reasons for discontinuation were progressive alopecia (15%, 95% CI 10-20%) and reasons unrelated to SC (9%, 95% CI 5-13%). The most frequent AEs leading to SC discontinuation were headache (4%, 95% CI 2-6%), cold intolerance (4%, 95% CI 3-5%), and general discomfort (4%, 95% CI 2-7%). Secondary analysis of scalp metastases yielded an incidence of 0.15% (95% CI 0.05-0.47%). Analysis of FDA Manufacturer and User Facility Device Experience (MAUDE) database medical device reports revealed that user error contributed to cold thermal injuries. Prevalence estimates were limited by significant heterogeneity between studies, reflecting variations in study methodology and real-world SC practices. CONCLUSION/CONCLUSIONS:SC is generally well tolerated with minimal safety concerns. Clinical comfort strategies like supportive medications and improved patient education could enhance SC tolerability and support its implementation.

Patients with, survivors of, and women at increased risk of breast cancer may experience various hair loss disorders, including those related to cancer treatments (such as chemotherapy- or endocrine therapy-induced alopecia), alopecia areata, androgenetic alopecia, and cicatricial alopecias. In the USA, approximately 1 in 8 women (13.1%) will develop breast cancer during their lifetime, emphasizing the importance of understanding safe treatment options for this population. Management of scarring and nonscarring alopecias in patients with or those at high risk of breast cancer requires the selection of therapies that do not impact breast cancer risk, treatment, or outcomes. In this review, we examine the safety of common medications used in the treatment of alopecia areata, androgenetic alopecia, and cicatricial alopecias with regard to breast cancer. We provide evidence-based recommendations for the use of these treatments in patients with and women at elevated risk of breast cancer while highlighting areas where further research is needed.

Disorders affecting the hair follicle (HF) and pilosebaceous unit impose psychosocial and financial burdens on patients and may signal risk for other medical conditions. Human genetic studies help to identify key physiological mechanisms that govern health and are increasingly used to improve drug development. GWASs identify genetic variants that are common in the population and implicate disease mechanisms that are widely shared among patients. In this study, we synthesize knowledge about the biology of the pilosebaceous unit that has been derived from GWASs of hair-related diseases. We identify the key genetic drivers and reveal fundamental biological themes that cut across diseases to identify crucial regulators of HF health.