The Pathogenesis and Treatment of Alopecia Areata

During his session, “Alopecia Areata: Clinical Challenges and Emerging Treatments,” presented at Dermatology Week 2022, Brett King, MD, PhD, discussed the lack of effective treatment for alopecia areata (AA), and recent data on utilizing JAK inhibitors for treatment.

He started by discussing the evolving understanding of AA pathogenesis. He noted that for a very long time—since the early 1900s—the belief was that AA was a result of stress. In fact, this perception was very hard to deviate from even despite evidence from a 1982 study showcasing that the hair bulbs are surrounded by lymphocytic infiltrate.

With the evidence from the 1982 study, treatment algorithms advanced in which the treatments for AA consisted of the following in 2010:

• Intralesional corticosteroids
• Topical corticosteroids
• Topical minoxidil
• Topical immunotherapy
• Systemic corticosteroids
• Cyclosporine
• Methotrexate
• Psychosocial support

Dr King then presented a study that took a look at traditional systemic immunosuppressants, such as:

• Cyclosporine
• Methotrexate
• Azathioprine

He noted that the study had a very weak definition of response, which only looked at the continuation of therapy after 12 months. The results he focused on were the responders to concurrent prednisolone, where he noted that about two-thirds of patients need concomitant systemic corticosteroids.  

“So, then we would essentially need a kind of transplant regiment of immune suppression to achieve some definition of response,” he noted.

Relooking at AA pathogenesis, Dr King shared that some advances had been made leading up to a study conducted in 2014, which showed that secretion of IL-15 in follicular epithelial cells recruits and activates cytotoxic T-cells. “The cytotoxic T-cells secrete IFN-g that binds its receptor on the follicular epithelial cell, which leads to an additional secretion of IL-15. These results showed that this cyclical action leads to inflammation and subsequent hair loss.”

During the final portion of his presentation, Dr King shared recent reports of JAK inhibitor therapy for AA, including:

• The safety and efficacy of the JAK inhibitor tofacitinib citrate
• Oral ruxolitinib for induction of hair regrowth in patients with moderate to severe??? AA
• Tofacitinib for the treatment of severe AA and variants in adolescents and preadolescent children
• Ruxolitinib for the treatment of severe alopecia areata

“Every single week, every single month, there are new report series of patients treated with off-label use of JAK inhibitors showing quite dramatic results,” Dr King shared. He added that the results, presented in a series of images he showcased, have been astounding and have had an important impact on patients who went from being ghosts of themselves to living a relatively normal life.

Reference
King B. Alopecia areata: clinical challenges and emerging treatments. Presented at: Dermatology Week 2022; May 11-14, 2022; Virtual.