Alopecia areata can have devastating effects on patients, but a greater understanding of its pathophysiology has led to the development of new treatment options.
Alopecia areata (AA) is a chronic autoimmune condition that damages the hair follicles. It typically presents with sharply defined round patches of nonscarring hair loss on the scalp.1 However, it can also affect the eyebrows, lashes, facial hair, and nails, and it can progress to alopecia totalis (total scalp hair loss) or alopecia universalis (total body hair loss). AA can have devastating effects on patients, but a greater understanding of its pathophysiology has led to the development of new treatment options. Here are 3 things you should know about managing alopecia areata.
1. AA can have a profound psychosocial impact.
With a lifetime incidence risk of approximately 2%, AA is the second most common cause of hair loss, behind androgenetic alopecia, and it affects men and women comparably.2-4 Up to 88% of patients experience their initial episode of AA prior to age 40 years, with spontaneous remission rates between 30% and 50% within the first 6 to 12 months of onset.2,5 Overall, the incidence of relapse is 85% and approaches 100% over 20 years.
Patients with AA have a higher prevalence of depression, anxiety, and sleep problems than the general population.6,7 In a cross-sectional online survey study, 62% of patients said AA caused them to make different major life decisions with respect to relationships, education, or career.8 Additionally, 85% said that it is a daily challenge to cope with AA, and 47% reported anxiety and/or depression.8 Results of a systematic review showed that patients with AA consistently exhibit poor health-related quality of life, similar to patients with other chronic dermatologic diseases, including atopic dermatitis and psoriasis.9
The concerns of stigma in patients with AA may not be unfounded. A survey of 2015 laypersons who were shown 3 images of the same person with varying amounts of hair found that 30% of respondents thought of those with severe hair loss as sick, and 27% viewed them as unattractive. Stigma increased as degree of hair loss increased.10
2. The pathogenesis of AA is gaining new insights.
The normal human hair growth cycle consists of 3 phases: anagen (active hair/follicular growth), catagen (regression/follicular involution), and telogen (follicular rest and shedding).11 In AA, autoimmune-mediated damage to the hair follicle in the anagen phase leads to premature transition to the catagen and telogen phases and subsequently to loss of hair.
The anagen hair follicle normally has immune privilege due to production of local immunosuppressants and downregulation of major histocompatibility complex class I proteins, among other factors.12 Breakdown of immune privilege of the hair follicle (resulting from genetic, environmental, and immunologic factors) is thought to be a key element in the pathophysiology of AA.13 With the collapse of immune privilege, autoreactive CD8-positive and natural killer (NK) group 2D–positive (NKG2D+) T cells can attack follicular epithelial cells.14
When these T cells bind to autoantigens at the follicle, they release the cytokine interferon-γ (IFN-γ), which is a key driver of AA pathogenesis.15 In response to IFN-γ, follicular epithelial cells then signal via the Janus kinase (JAK)/signal transducer and activator of transcription (JAK-STAT) pathway to upregulate γ-chain cytokines, including interleukin (IL)-2 and IL-15.16 IL-2 and IL-15 are known drivers of cytotoxic T-cell activity.17 JAK-mediated production of IL-15 promotes further inflammation and T-cell activation, causing additional release of IFN-γ via JAK signaling in a positive feedback loop. These cytokines and chemokines further recruit CD4-positive T cells and natural killer cells to the hair follicle, leading to dystrophy.18
3. The management of AA is individualized.
AA has historically been treated with intralesional or topical corticosteroids.11 However, the efficacy of these treatments is limited, and few randomized controlled trials have been performed. Additionally, safety concerns of local corticosteroids include telangiectasias and skin atrophy. In a cross-sectional online survey study, patient-cited reasons for discontinuing AA treatment included adverse effects and lack of efficacy.8
Newer agents in development target the cytokines involved in AA pathogenesis. JAK inhibitors are small-molecule drugs that block JAK enzymatic activity, thereby blocking cytokine signaling and STAT activation.19 This is thought to prevent the upregulation of IFN-γ. Tofacitinib, a first-generation JAK inhibitor, has been reported to improve hair growth in patients with AA in many small case-report and case-series studies, but a large randomized controlled trial is lacking.11 The Table20-24 provides a summary of other JAK inhibitors studied for use in AA.
Baricitinib is currently the only FDA-approved JAK inhibitor for AA.25 A meta-analysis of the use of tofacitinib, ruxolitinib, and baricitinib in patients with AA found that 72% of 289 cases responded to therapy, with a mean time to hair growth of 2 months.26
Treatment algorithms for AA are based on patient age, disease activity and severity, and treatment response.27 When managing patients with AA, it is important to consider a shared decision-making approach—taking into account disease severity, quality of life, comorbidities, and long-term efficacy and safety—to provide the best possible treatment and improve patient outcomes.
8. Mesinkovska N, King B, Mirmirani P, Ko J, Cassella J. Burden of illness in alopecia areata: a cross-sectional online survey study. J Investig Dermatol Symp Proc. 2020;20(1):S62-S68. doi:10.1016/j.jisp.2020.05.007
11. Dillon KL. A comprehensive literature review of JAK inhibitors in treatment of alopecia areata.Clin Cosmet Investig Dermatol. 2021;14:691-714. doi:10.2147/ccid.S309215
26. Rattananukrom T, Suchonwanit P. Are drug treatment strategies really effective against alopecia areata? Expert Opin Pharmacother. 2021;22(3):257-260. doi:10.1080/14656566.2020.1854728
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This activity was written by Physicians’ Education Re-source®, LLC (PER®), editorial staff under faculty guidance and review.
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Disclosures (Dr King):
Consultant: AbbVie, AltruBio, Almirall, AnaptysBio, Arena Pharmaceuticals, Bioniz Thera-peutics, Bristol Myers Squibb, Concert Pharmaceuticals, Equillium, Horizon Therapeutics, Incyte, Janssen Pharmaceuticals, LEO Pharma, Eli Lilly and Company, Otsuka/Visterra, Pfizer.
The staff of Physicians’ Education Resource®, LLC, have no relevant financial relationships with ineligible companies.
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Release Date: October 1, 2022
Expiration Date: October 1, 2023
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