INTRODUCTION
Androgens, genetic susceptibility, chronic inflammation, oxidative stress, internal and external environmental triggers such as ultraviolet light, pollutants, aging, poor nutrition, as well as mediators of psycho-emotional stress (eg, cortisol and corticotropin releasing hormone) all contribute to dysregulation of complex follicle biology. Disruption of immune pathways affecting the follicle occurs through increased expression of pro-apoptotic and pro-inflammatory cytokines, perifollicular micro-inflammation, and release of reactive oxygen species (ROS). As we accept the multi-factorial nature driving hair loss, we can adopt new strategies to combat it, by aiming not at one, but at multiple targets. The rationale for this paradigm shift in hair loss therapy is the scope of this article. Herein is an update on our current understanding of hair physiology and the factors that have been scientifically demonstrated to influence hair follicle homeostasis and contribute to hair loss pathology.Hair loss is chronic and progressive without treatment, affecting at least 50% of women by age 50 and 40% of men by age 35 (progressing to up to 70% in later life).1-3 Hair is an important part of our appearance and social communication. It is therefore no surprise that its loss can cause significant psychological trauma in patients, which is further precipitated by the limited available treatment options that produce only variable results with chance for side effects.2,4 Currently the only two FDA-approved drugs for hair loss are finasteride and minoxidil in men and only minoxidil in women.5,6 The reason for lack of sustained, comprehensive, efficacious, and side effect-free therapies to date, may be the underappreciation of the impact and interplay of the multiple factors that influence the immunology and signaling pathways that regulate hair follicle biology.As dermatologists we’ve traditionally segmented hair loss according to distinct causes and morphology, inflammatory vs. non-inflammatory, genetic vs. acquired, scarring vs. non-scarring, androgen-mediated vs. not.7,8 This view has led to the design and development of drugs that target only single mechanisms, as exemplified by finasteride that inhibits production of dihydrotestosterone (DHT). However, recent research suggests that hair loss is multi-factorial and there may be more similarities than differences across the hair loss disorder spectrum. There is mounting evidence that just like most multigenic, chronic systemic and cutaneous disorders, hair loss is the result of an accumulation of multiple factors – genetic and environmental – that lead to the final molecular pathophysiology resulting in dysregulation of signaling pathways and inappropriate immune and inflammatory responses.5,7-10 Chronic inflammation at the level of the follicle appears to be a common thread in all types of hair loss – a view supported by the wealth of research showing that even in traditionally ‘non-inflammatory alopecias’ like
