Clinical Challenges and Emerging Treatments in Alopecia Areata

In his session, “Alopecia Areata: Clinical Challenges and Emerging Treatments,” on the second day of Fall Dermatology Week 2022, Brett King, MD, PhD, discussed the clinical challenges of alopecia areata (AA), including terminology and disease severity classification, the unmet need for effective treatments, and emerging data on Janus kinase (JAK) inhibitors to treat AA.

Dr King started by stating that AA is typically a clinical diagnosis. A positive pull test, as well as exclamation mark hairs and a yellow-dot pattern on dermoscopy can help confirm the diagnosis. In some cases, a biopsy may be helpful. Histopathologic features include peribulbar lymphocytic inflammation. He noted that differential diagnosis is the first challenge in AA.

He highlighted other clinical challenges, such as nomenclature and classification of AA, disease severity classification, how to treat severe disease, understanding the rate of spontaneous remission, and treatment of patients with polyautoimmunity. Classification of AA is on a spectrum, from a few patches of disease to band-like hair loss and top-of-head involvement, all the way to alopecia totalis (complete loss of scalp hair) and alopecia universalis (complete loss of scalp and body hair). There can be eyebrow, eyelash, beard, and nail involvement. Dr King noted, “The vast majority of patients have limited or more exuberant patchy disease, but we call them all the same thing. We don’t really have a way of thinking about mild, moderate, and severe.” He added, “It is time to abandon the terms alopecia totalis and alopecia universalis. They are being used in wildly different ways.”

There can be any degree of scalp hair loss by itself or involvement of other hair-bearing areas and nails. Developed in 2004, the Severity of Alopecia Tool, or SALT, score is an assessment of the amount of scalp hair loss. Alternatively, there is the AA Investigator Global Assessment developed as part of clinical trials, which also assesses disease severity by amount of scalp hair loss but “puts it into buckets,” such as severe and very severe, and is more user friendly. The Alopecia Areata Scale is a newer holistic assessment of AA severity, which uses mild, moderate, and severe categories, along with eyebrow or eyelash involvement, inadequate response after at least 6 months of treatment, diffuse positive hair pull test consistent with rapidly progressive AA, and negative impact on psychosocial functioning resulting from AA.

Dr King then moved on to traditional treatment of more severe disease. One study of systemic therapies, such as dexamethasone, for alopecia totalis or alopecia universalis, at a mean duration of therapy of 12.9 months, showed that 71% of patients achieved 75% or more hair regrowth. But two-thirds of the patients had hair loss again when they stopped treatment. He also discussed cyclosporine, methotrexate, and azathioprine, used concurrently with prednisolone to achieve 58%, 64%, and 67% response, respectively. “All of this highlights the profound unmet need for effective treatments,” Dr King remarked.

There is an evolving understanding of AA pathogenesis. Secretion of IL-15 in follicular epithelial cells recruits and activates cytotoxic T-cells, which then secrete IFN-γ, binding its receptor on the follicular epithelial cell and leading to further secretion of IL-15. This cyclical action results in inflammation and subsequent hair loss. “Treating severe AA is about achieving normal,” said Dr King.

Randomized controlled trials of off-label JAK inhibitors in AA have included topical ruxolitinib 1.5% cream, topical delgocitinib ointment, ritlecitinib, deuruxolitinib, and baricitinib. Topical ruxolitinib 1.5% cream and topical delgocitinib ointment were ineffective in the treatment of AA, but deuruxolitinib, ritlecitinib, and baricitinib have been effective. Oral minoxidil for AA has also been considered.

Randomized controlled trials have also ed to an understanding of the rate of spontaneous remission. For patients with limited scalp hair loss, spontaneous remission is common, but for patients with severe scalp hair loss, only 2% to 4% experience spontaneous remission.

A major risk factor for AA is genetics. Twenty percent of patients can identify a family member who has AA. There are 18 genes commonly associated with AA, and most of them are found in association with other autoimmune diseases. Patients with AA have comorbidities such as autoimmune thyroid disease and atopic dermatitis. Polyautoimmunity is the presence of more than 1 autoimmune disease in a single patient.

Dr King concluded, “AA is a complex, polygenic autoimmune disease that frequently has autoimmune comorbidity.” He added, “JAK inhibitors are showing promise in clinical trials for AA.”

Reference

King B. Alopecia areata: clinical challenges and emerging treatments. Presented at: Dermatology Week 2022; September 14-17, 2022; Virtual.