Alopecia

Alopecia, or hair loss, affects more than 80 million people in the United States, and the nonscarring alopecias are categorized as diffuse, patterned or focal. ^[1] Androgenetic alopecia (AGA), also called male or female pattern hair loss, is the most common form of alopecia and arises from an excessive response to androgens. ^{[2] [1]} AGA typically presents as a receding frontal hairline in men and as diffuse thinning with frontal hairline retention in women. ^[3] Alopecia areata is a distinct, chronic autoimmune form of non-scarring hair loss estimated to affect 2% of people over their lifetime, ranging from a single small round patch to full scalp and body hair loss. ^[4] Its most extensive forms are alopecia totalis (complete scalp hair loss) and alopecia universalis (loss of hair over the entire body). ^{[5] [6]} Telogen effluvium belongs to the diffuse alopecias, which are usually self-limited and depend on stopping the underlying cause, such as stress. ^[1] Patients with moderate to severe hair loss are more likely to have accompanying anxiety and depression and lower work productivity and quality-of-life scores. ^[1]

AGA is driven by genetic predisposition and excessive follicular sensitivity to androgens, leading to the progressive conversion of scalp terminal hair into vellus hair. ^[7] The process is primarily mediated by 5-alpha-reductase and dihydrotestosterone (DHT), which cause follicle miniaturization and shortening of successive anagen cycles. ^[3] AGA is polygenic: genome-wide association studies have identified more than 380 genomic loci, including genes in androgen and WNT pathways, while the molecular basis of AGA in women remains undetermined. ^[8] Beyond androgen metabolism, current models of AGA pathogenesis also include inflammation, fibrosis and impaired energy metabolism. ^[9] In alopecia areata, loss of the immune privilege of the hair follicle leads to local follicle-associated inflammation, with multiple genetic and environmental factors contributing. ^{[4] [6]} Pro-inflammatory cytokines implicated in alopecia areata, including interleukin-15, interferon-gamma and the Th2 cytokines IL-4 and IL-13, signal through the Janus kinase (JAK) pathway, which is the rationale for JAK inhibition.

A comprehensive history and physical examination with targeted laboratory testing may reveal malnutrition, autoimmune disease or endocrine disease as the cause of hair loss. ^[1] Hair loss is one of the manifestations of iron deficiency, for which serum ferritin is the most efficient diagnostic test. ^[12] Deficiencies of vitamin B, vitamin D, iron and zinc have been associated with an increased risk of AGA, but the evidence is not entirely consistent and some studies report no significant association. ^[13] AGA most often involves frontal, mid-scalp and crown follicles in postpubescent men and postmenopausal women, and only rarely premenopausal women or prepubescent individuals. ^[8] Alopecia areata severity is graded with the Severity of Alopecia Tool (SALT) score or the Alopecia Areata Scale, and a SALT score of 20 or more is a commonly accepted indication for systemic therapy. ^[5] Alopecia areata is associated with atopic, autoimmune and psychological comorbidities. ^[4]

Topical minoxidil and oral finasteride are the only two FDA-approved drugs for AGA, although one review also lists low-level light therapy among the FDA-approved therapies. ^{[2] [7] [3]} In meta-analysis, finasteride 1 mg/day increased total hair count versus placebo by a mean of 12.4 hairs/cm2 at 24 weeks and 16.4 hairs/cm2 at 48 weeks. ^[14] Finasteride is associated with sexual adverse events such as erectile dysfunction and decreased libido, depression was added to its FDA label in 2011, and a post-finasteride syndrome can persist after the drug is stopped. ^{[14] [7]} Oral minoxidil is not FDA-approved for hair loss and is used off-label, with low doses of 0.5-5 mg/day possibly safe and effective for female pattern hair loss and chronic telogen effluvium, and with dose-dependent hypertrichosis and cardiovascular effects. ^[15]