Background
Alopecia areata (AA) is an autoimmune disease characterized by discrete patches of nonscarring hair loss. Although AA does not involve other organ systems, the disorder can cause significant emotional and social distress, especially in its more severe manifestations – alopecia totalis (complete loss of scalp hair) and alopecia universalis (total loss of body hair). The pathogenesis of AA remains enigmatic, but the hair loss is triggered by perifollicular and intrafollicular mononuclear cell infiltrates, composed primarily of activated CD4+ and CD8+ T cells. AA often remits spontaneously, but lymphosuppressive and lymphotoxic treatments such as oral and intralesional corticosteroids facilitate hair regrowth in up to 60% of cases.[1] Oral corticosteroid use is limited by systemic toxicity, while intralesional corticosteroids are difficult to administer to large areas and may induce local skin atrophy.
Hanson and colleagues[2] recently noted that topical bexarotene, a synthetic retinoid specific for the retinoic acid X nuclear receptor, yielded significant hair regrowth when used to treat patients with follicular mucinosis or folliculotropic mycosis fungoides. They postulated that this effect may be caused – at least in part – by bexarotene’s ability to induce T-cell apoptosis[3] and theorized that topical bexarotene may also induce hair regrowth in AA.
Study Summary
To test this hypothesis, Talpur and colleagues conducted a prospective “half-head” trial of 1% bexarotene gel, applied twice daily to areas of AA for up to 6 months. They enrolled 42 patients (31 women; median age 37.5 years; 33 whites, 6 Hispanics, 3 blacks) with patchy AA (n = 34), alopecia totalis (n = 3), and alopecia universalis (n = 5). The investigators used a Physician Global Assessment of improvement from baseline as their primary outcome measure; patients who experienced greater than 50% improvement were considered to be responders. In addition, signs of systemic and local retinoid toxicity were assessed at multiple timepoints. Patients began applying topical bexarotene monotherapy after a therapeutic washout period of at least 1 month. Patients who responded to the first 24 weeks of treatment could apply bexarotene gel to both sides of their scalp for an additional 6 months.
During the 24 week half-head treatment phase, the investigators noted the following:
Five of 42 patients (12%) showed at least 50% hair regrowth on the treated side.
Six of 42 patients (14%) showed at least 50% regrowth on both treated and nontreated sides.
The treatment was well tolerated, with 31 patients experiencing only mild local skin irritation; 4 patients developed significant irritation (skin vesiculation).
There was a trend towards irritation being associated with hair regrowth, because 82% of responders developed irritation on 1 or both sides of their scalps.
One patient with alopecia universalis showed no hair regrowth during the 5 months of bexarotene gel application; however, when he started oral prednisone, he developed significant regrowth only on the half of his scalp that had been pretreated with bexarotene.
Viewpoint
Patients with AA carry a higher risk of developing other autoimmune or atopic disorders,[4] although AA does not affect other organ systems. Nevertheless, patients with AA experience significant distress from this condition, especially in cases of widespread hair loss. Treatment remains a challenge because the most effective options (pulse corticosteroids, oral cyclosporine) carry significant risks. In this context, a new topical therapy would be welcome.
In the small study reviewed above, Talpur and associates provide some evidence that topical retinoid bexarotene may – at least in a subset of patients with AA – induce significant hair regrowth. It is intriguing that many of the study participants experienced hair regrowth that was not confined to the side of the scalp that had been treated with topical bexarotene. The study authors speculate that this may be either a consequence of diffusion of the drug or patient noncompliance (application to both sides against the protocol). Unfortunately, the study did not include a placebo control gel, precluding the ability to rule out spontaneous regrowth. As the investigators correctly note, future studies should include a placebo in order to clarify the true efficacy of this promising new topical therapy. Such studies should also address the possibility of synergistic therapies combining topical bexarotene with other established treatments, such as corticosteroids (both intralesional and systemic) and topical minoxidil.[5]