Clinical Challenges and Emerging Treatments of Alopecia Areata

On the last day of the 9th Interdisciplinary Autoimmune Summit, Dr Brett King, MD, PhD, summarized and addressed the clinical challenges of alopecia areata (AA), including terminology and disease severity classification; described the unmet need for effective treatment of AA; and evaluated emerging data on JAK inhibitors for treatment of AA.

Dr King kicked off the session with the clinical challenges of AA. “I think these challenges are interesting in the context of emerging therapies and… hopefully FDA approved therapies for [AA] in the near future.” 

One of the challenge Dr King mentioned is differential diagnosis. “We typically make the diagnosis clinically and we should probably be doing more biopsies. It’s critically important to recognize when we don’t know something and to do a biopsy.”

Another challenge Dr King explained is nomenclature or classification of AA. “[AA] disease can involve any hair-bearing surface area. So, eyebrows can be involved, eye lashes can be involved. These can be involved independently of one another, or it can be involved together. The beard area can be involved in males, and the nails being another keratinized structure like the hair can also be involved.”

Furthermore, Dr King pointed out that “the nomenclature we have right now is inexact. Someone with 1% hair loss is called the same thing as somebody with 80% hair loss, all AA. And we don’t have a way to qualify that as mild, moderate, or severe, so we’ve very inexact nomenclature. And it’s confused because the terms alopecia totalis (AT) and alopecia universalis (AU) are being used in wildly different ways.” Therefore, referring to a study, Dr King suggested, “We really need to let go, I think, of this concept of AT/AU and being one in the spectrum, and instead thinking about there being limited hair loss and severe hair loss.”

Next, Dr King conceptualize the severity of AA. The instruments available to describe the spectrum are the Severity of Alopecia Tool, or SALT, developed and published in 2004, and the Alopecia Areata Investigator Global Assessment (AA-IGA). However, “for holistic assessment of AA severity, [the] Alopecia Areata Scale (AASc) can be used, wherein scalp hair loss is classified as mild (≤ 20%), moderate (21%–49%), and severe (50%–100%).” Additionally, for diagnosis, Dr King also recommended to, “increase mild or moderate AA severity rating by one level if one or more of the following is present in a patient: eyebrows or eyelashes involvement, refractory to treatment, rapidly progressive AA, and psychosocial impairment.”

For the treatment of more severe disease, Dr King explained the evolving understanding of AA pathogens from 1950 to 2014. Moreover, he described our understanding of the rate of spontaneous remission. He said, “For the first time, with randomized controlled clinical trials, we now have very detailed and accurate knowledge about the rate of spontaneous remission.” He added, “In [the] case of limited hair loss, spontaneous remission is not uncommon. Severe hair loss is chronic and spontaneous remission is rare.”

Lastly, Dr King discussed a final clinical challenge, treatment of patients with polyautoimmunity. “It’s [been] known since 1990s that genetics are an important part of [AA]. [Approximately] 20% of the patients with AA can identify a family member who has AA. Concordance among monozygotic twins is 55%.” He further added, “The genome-wide association study (GWAS) highlighted 18 genes that are commonly associated with AA… Many of these genes are also associated with other autoimmune diseases. That ultimately underlies the comorbidities [among] patients with AA.”

Dr King concluded the session with the following summaries:

• AA is a complex polygenic autoimmune disease and frequently has autoimmune comorbidity.
• The terms alopecia totalis and alopecia universalis have limited utility.
• Disease severity may be assessed using the AA-IGA or AASc.
• Spontaneous remission is rare for patients with severe disease.
• Conventional treatments, including systemic corticosteroids and immunosuppressants, are not particularly effective in treatment of severe AA.
• The immunopathogenesis involves IL-15 and IFN-γ, which signal through the JAK-STAT pathway.
• JAK inhibitors are showing promise in clinical trials for AA.

Reference
King B. Alopecia areata: clinical challenges and emerging treatments. Presented at: Interdisciplinary Autoimmune Summit; April 9–11, 2022; Virtual.